The Role of Genetics in Inherited Colon Cancers A guide to Research, Literature, and Exploration Kelly LaVoice This guide

presents a collection of literature and reference materials for graduate students researching in the field of hereditary/inherited forms of colorectal cancer. Genetic research became increasingly prominent in the early 1990s as scientists developed new technologies for genomewide DNA mapping and has continued to flourish. Inherited colon cancers are genetic disorders caused by abnormalities in specific genes or chromosomes that are often passed down through DNA from parents to their children. This guide will begin with a brief introduction to important aspects of the topic before identifying recommended reading in forms of reference sources, journal articles, books, patents etcetera. Key researchers and clinicians in the field, as well as important organizations and the conferences they hold, will also be discussed. This literature guide is meant to serve as an introduction for graduate students, so I recommend students completing dissertation work or other detailed assignments schedule a research session with one of the medical or science librarians. Colon cancer has the second highest death rate of cancers in both men and women in the United States. The American Cancer Society estimates that 143,460 people will be diagnosed in 2012 and that 51,690 will die from colon cancer in the United States (Colon Cancer Alliance Statistics). It is extremely important for adults over 50 to have regular screenings and colonoscopies, for 90% of new cases and 95% of deaths from colon cancer occur in people 50 or older (Colon Cancer Alliance Statistics). When colon cancer is found early treatment has the highest chance of being effective. In many cases, screening can prevent colon cancer by finding and removing polyps before they become cancer (Colon Cancer Alliance Statistics). The majority of colon cancers are not found until it has spread to regional tissues or other organs and patients start experiencing significant physical symptoms. While rates for colon cancer in adults 50 and older have been declining, incidence rates in adults younger than 50 years has been increasing (Colon Cancer Alliance). When individuals develop colon cancer at young ages and have immediate family members who also developed colon cancer before reaching the age of 50, clinicians may conduct genetic testing to determine if there is an inherited mutation making the individuals more susceptible to colon cancer. The large majority of colon cancers are caused by a genetic mutation for that individual, who is not born with a hereditary link to cancer. Less than 5% of total colon cancer cases are suspected to be inherited forms of cancer (Colon Cancer Alliance). Individuals with a first-degree

Colon Cancer Guide 2 relative who was diagnosed with colon cancer have a 2 to 3 times higher risk of developing colon cancer than the average individual without a family history. If a parent has a hereditary gene mutation, each child with the affected parent has a 50% chance of inheriting that gene (equal rate for females and males) (NHGRI, Learning About Colon Cancer). Research has been focused on several identified genetic mutations with a high susceptible to two types of colon cancer: familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC), which is also called Lynch Syndrome (NHGRI, Learning About Colon Cancer). HNPCC and FAP exert strong effects, so they were relatively straightforward for researchers to discover. Most in the field believe that other genes may increase susceptibility to colon cancer and have yet to be discovered, because a number of dependent relationships between on multiple genes must occur and may exert more subtle, weaker effects then the strong effects of HNPCC and FAP (NHGRI, Learning About Colon Cancer). FAP is caused by a mutation on the APC gene (located on the 5th chromosome). At this point in time, over 300 unique mutations have been identified by scientists on the APC gene. Individuals who inherit one of the mutations on the APC gene have a nearly 100 percent chance of developing colon cancer by age 40 (NHGRI Learning About Colon Cancer). Another identified syndrome is HNPCC, which is also called Lynch Syndrome. Individuals diagnosed with one of the 5 discovered mutation genes for NHPCC have an 80% risk of developing colon or rectal cancer (NHGRI, Learning About Colon Cancer). 5 HNPCC gene triggers have been discovered; MSH2, MSH6 and PMS1 on chromosome 2, MLH1 on chromosome 3, and PMS2 on chromosome 7. Mutations in MSH2 and MLH1 are the most common mutations that cause HNPCC (NHGRI, Learning About Colon Cancer). The role of PMS1 is still being researched, for the mutation was not found in all members of a family with HNPCC in an authoritative research study (NHGRI, Learning About Colon Cancer). The following resources can be used for learning more about both forms of inherited colon cancer as well as environmental factors that may also be a link triggering some colon cancer cases. -Websites quoted in guide Learning About Colon Cancer. (2012). National Human Genome Research Institute. http://www.genome.gov/10000466). Colon Cancer Statistics (2012). Colon Cancer Alliance. http://www.ccalliance.org/colorectal_cancer/statistics.html

Colon Cancer Guide 3 Books and Text Books: These materials were chosen by comparing cancer collections in highly esteemed medical librarys catalogs, including Harvard, Johns Hopkins, University of Pennsylvania, Stanford, Yale, University of Washington St Louis and Columbia. Some of these materials were also reviewed in prominent science or library publications; these resources will have the review articles bibliographic information included as well. To access these materials, complete a search in the library catalog; you can find a guide on how to search for books from a link on our librarys homepage.

Church, JM and Casey, G. (2003). Molecular Genetics & Colorectal Neoplasia: A Primer for the Clinician (Developments in Oncology). New York: Springer. ISBN-13: 978-1402076114 Describes how a better understanding of genetics will allow clinicians to better serve affected patients. This resource details genetic testing techniques as well as colon cancer screening devices. The use of medical jargon suggests this text is intended for geneticists, epidemiologists, clinical physicians, surgeons, oncologists, and medical researchers at academic institutions. Ellis, CN. (2010). 2nd edition. Inherited Cancer Syndromes: Current Clinical Management. New York: Springer. ISBN-13: 978-1441968203 This resource is intended for practicing clinicians to better understand advances in genetic testing and available resources from the last decade. The first half of the text focuses on assessing risks of inherited cancers through genetic counseling and risk analysis processes. Specific chapters focus on colonic-polyposis syndromes, hereditary nonpolyposis colorectal cancer, and multiple endocrine neoplasias (which often occur in women with Lynch Syndrome). The second half of the resource touches upon economic, moral, and legal implications of genetic testing. -Review: Burt, RW. (November 2004). Inherited Cancer Syndromes: Current Clinical Management. New England Journal of Medicine; 351:2137-2138. Gearhart, SL (ed) and Ahuja, N (ed). (2010). Colorectal Cancer. Philadelphia: Saunders/Elsevier. ISBN 9781416046868 Focuses on helping clinicians to improve their ability to diagnose cancer symptoms earlier and increase success with treatment. The book is written as a guide for clinicians and offers practical advice about patient care resources under financial restraints. It details new gene therapies to reevaluate their patients potential colon cancer risks. This resource has detailed color photographs and an accompanied CD-ROM with video clips about diagnostic testing.

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Levin B (ed.), Ades, T (ed.), and Couric, K (intro). (2005). American Cancer Society's Complete Guide to Colorectal Cancer. New York: American Cancer Society. ISBN-13: 978-0944235553 Intended to be of interest to both patients, individuals without a medical background, and clinicians; however the sophisticated medical jargon would be a challenge for lay persons. The authors are all academic researchers who focus on improve techniques for screening, detection, treatment and alternative therapies. Review: James, J. (2006). American Cancer Society's Complete Guide to Colorectal Cancer/Living with Colon Cancer: Beating the Odds. Library Journal, 131(2), 98-99. Potter JD and Lindor, NM. (2009). Genetics of colorectal cancer. New York, NY: Springer. ISBN: 9780387095677 Begins with a focus on epidemiology and related studies using mice. The next sections focus on the APC gene mutation, BLM mutation, chromosomes 8q24 and 9p24, DNA methylation in colorectal cancer, tumorigensis, and chromosomal-instability pathways. Key differences between FAP and Lynch syndromes in case studies of adults and juveniles are discussed. This is a very sophisticated medical resource for those with a strong background in biology and chemistry. Rodreiguez-Bigas, MA (ed), Cutair R(ed), Lynch PM (ed), Tomlinson I (ed), and Vasen, HFA (ed). (2010).Hereditary Colorectal Cancer. Anderson Solid Tumor Oncology Ser. New York: Springer Science. Provides a historical framework necessary for understanding genetic mapping technologies and hereditary colon cancers. The book addresses its audience as surgeons, colorectal specialists, oncologists, gastroenterologists, and geneticists. Very well-balanced coverage between history and current research. The authors also provide clinical algorithms for diagnosis and treatment. Additionally, it discusses the importance of genetic counselors working with genetically predisposed patients to help with the creation of genetic databases for families with FAP and Lynch Syndromes. One of the authors, PM Lynch, discovered the specific gene mutation for Lynch Syndrome and the syndrome was named after him. Rozen, P, Young,GP, Levin, B, and Spann, SJ. (2002). Colorectal Cancer in Clinical Practice: Prevention, Early Detection and Management. London: Martin Dunitz. ISBN: 1-901865-87-8 Written with nurses and clinicians in mind, this book focuses on resources for improving earlier detection of colon cancers. New screening methods and other tools for prevention are discussed in detail. While medical jargon is used, the book is written in a clear, concise style that those without a detailed medical background could comprehend. Swan, E. (2006). Colorectal Cancer. London: John Wiley & Sons. ISBN 9780470031681 -Written for nurses by a nurse working with doctors and surgeons to treat patients with colon cancer. Discusses sporadic and hereditary forms as well as physiological factors in coping with a colon cancer diagnosis and treatment -Review: Cunningham, S. (2006). Colorectal Cancer. Nursing Standard, 20(17), 37.

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Text Books: Adami HO (ed.), Hunter D (ed.) and Trichopoulos D (ed.). (2002). Textbook of Cancer Epidemiology. New York: Oxford University Press. ISBN: 0-19-510969-4 -Focuses on how environmental exposures, genetics, and individual lifestyle choices and diets influence the risk of developing cancer. The authors state that the book is intended for students, cancer epidemiologists, and medical practitioners. While the first half of the book focuses on genetics, biomarkers, and descriptive cancer information, the second half of the book focuses on specific types of cancer. Concerning colon cancer, the authors discuss clinical synopsis, genetic and molecular epidemiology, somatic mutations, and other environment or lifestyle risk factors. Review: Bodice JD, Blot JW, and McLaughlin JK. (2003). Textbook of Cancer Epidemiology. New England Journal of Medicine; 348:2047-2048. http://www.nejm.org/doi/full/10.1056/NEJM200305153482026 Beauchemin N and Huot J. (2010). Metastasis of Colorectal Cancer. New York: Spring Science -Chapter 3 CRC Molecular Pathology: The Genetics of Colorectal Cancer by Katz and Grady is of particular interest to students researching FAP and HNPCC mutations. Provides recent developments that are not covered in some of the materials from the early 2000s. Very useful for understanding the technologies and theories behind genetic testing. Cassidy J (ed.), Johnston P (ed,), and Cutsem, EV (ed.). (2007). Colorectal Cancer. New York: Informa Health Care. ISBN: 978-0-8247-2835-9. Highly recommended by the New England Journal of Medicine as a quality text to be used in oncology classes or for students wishing to specifically focus on sporadic and inherited forms of colon cancer. The sophisticated use of jargon and medical concepts makes this resource challenging and appropriate for graduate level research. Review: Venook, AP. (2007).Colorectal Cancer. New England Journal of Medicine. 356:11891190 http://www.nejm.org/doi/full/10.1056/NEJMbkrev57863 Monsen RB (ed.). (2009). Genetics and ethics in health care: new questions in the age of genomic health. Silver Spring Maryland: American Nurses Association. This resource is a very interesting read for researchers interested in the social, environmental, political, and psychological factors involved in controversial genetic research, gene mapping, and using stem cells testing. A must read for anyone interested in practicing medicine concerning hereditary forms of cancer. Panno, J. (2010)Cancer: The Role of Genes, Lifestyle, and Environment (New Biology ser: Revised Ed). Facts on File. ISBN-10: 0816068488 -Very simple, conversational writing style. This book is a concise summary of how cancer cells grow and develop, while also touching upon the various genetic and environmental factors that play roles in several types of cancer. Phillis, Randall W., and Steve Goodwin. (2003). Biology of Cancer. San Francisco: Benjamin/Cummings. Part of the Benjamin Cummins Special Topics in Biology Series. Phillia and Goodwin, two professors from the University of Massachusetts, Amherst. It focuses on genetic effects of cancer, the cancer cell cycle and the evolution of tumor cells, and outline the 6 hallmarks of cancer cells. Interesting discussion about Hereditary vs. Sporadic Cancer and the

Colon Cancer Guide 6 development of technologies to screen individuals who believe their family may have inherited cancer. Souhami RL (ed.), Tnannock I (ed.), Hohenberger P (ed.) and Horiot JC (ed.). (2002).Oxford Textbook of Oncology (2nd ed). New York: Oxford University Press. ISBN: 0-19-262926-3 A general text focuses both common and rare forms of cancer. Excellent coverage of colon cancer. This book includes a detailed literature review on the history of genetic research and genome mapping. Review Schwartz RS. (2002). Oxford Textbook of Oncology. New England Journal of Medicine 347:150-151http://www.nejm.org/doi/full/10.1056/NEJM200207113470223 Weinberg, RA. (2006). The Biology of Cancer. Garland Science. ISBN-10: 0815340788 Discusses the importance of the history of modern molecular biology and how understanding DNA coding was necessary to begin to understand genetic cancers and the ways in which cancer cells grow. This textbook requires an initial background in biology, but is written in a very clear, concise style. Weinbergs book includes a cd-rom with PowerPoints and mp3s of lectures as well as JPEG files of all of the images shown in the book. Weinberg also includes six very helpful video models of key concepts, including RAS activation. REVIEW: Hawley, A T. and Pandolfi, P. (2007). Secrets of a killer. Nature Cell Biology, 9(11), 1218. doi:10.1038/ncb1107-1218 -Wei Q, Li L, and Chen DJ. (2007). DNA Repair, Genetic Instability, and Cancer. Hackensack, New Jersey: World Scientific Publishing. ISBN-13: 978-9812700148 This textbook is intended for graduate students studying biology of medicine. The authors focuses on DNA repair mechanisms and how the cell cycle checkpoint can detect and renew DNA damage. Very useful resource for students interested in applying biochemical analysis, structure details of DNA proteins, and genomic stability to studies of inherited colorectal cancer behavaiors. Reference Materials (Dictionaries & Encyclopedias) and Searching Resources Anderson, P. F., and Nancy J. Allee, eds. (2004). The Medical Library Association Encyclopedic Guide to Searching and Finding Health Information on the Web. 3 volumes. New York: Neal-Schuman. Recommended resource for students and medical practitioners looking for accurate, reliable and unbiased medical information on the internet. The first volume discusses search strategies, using thesauruses to create search terms, and linking procedures for MESH headings and subheadings. The second volume highlights searching for information about diseases and disorders, while the third volume focuses on environmental health factors. Bertino, Joseph R., ed. (2002). Encyclopedia of Cancer. (2nd ed). San Diego, CA: Academic. ISBN: 978-0-12-227555-5 Joseph Bertino, of the Cancer Institute of New Jersey (Robert Wood Johnson School of Medicine), focuses on discoveries and new techniques for screening, diagnosis, and treatments from the late 20th century to early 21st century. This resource is intended for graduate students, cancer researchers, and oncologists, and assumes readers are already familiar with many medical terms (MeSH headings) and procedures. Contains detailed entries on epidemiology, gene therapy, and oncogenes/tumor suppressor genes.

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Colon Cancer. (2012). The A.D.A.M. Medical Encyclopedia. Medline Plus from the National Cancer Institute. http://www.nlm.nih.gov/medlineplus/colorectalcancer.html Provides a brief definition of inherited colorectal cancers and interesting discussion of known and conjectured risk factors. The encyclopedia also links to frequently updated news sources on diagnosis, treatment, screening, alternative therapies, disease management, clinical trials, statistics, genetics, research, and health check tools. This resource will be ideal for students looking to learn more about contemporary aspects of colon cancer research and medical treatment without having to read an entire book. The NLM contains interaction videos and tutorials that may be of interest. Encyclopedia Britannica. (2012). Encyclopedia Britannica Inc. http://www.britannica.com/ Good overviews of familial cancer syndromes and hereditary nonpolyposis colon cancer. Online version is significantly more detailed and accompanied by illustrations. Finding Cancer Statistics (2012). National Cancer Institute. http://www.cancer.gov/statistics/finding Useful resource for using government and nonprofit webpages to find cancer statistics about the US. Includes links to various maps and charts displaying statistics (last updated in 2010). Fundukian, LJ. (2010). 3rd ed. The Gale Encyclopedia of Genetic Disorders (2 Volume Set). New York: Gale. ISBN-13: 978-1414476025 The entry on Hereditary Colorectal Cancer gives a very good overview and introduces readers to important vocabulary, chromosomes, and specific genes involved in the most common/well-understood forms of inherited colon cancer. Hitchcock, David. (2009). Patent Searching Made Easy: How to Do Patent Searches on the Internet & in the Library. 5th ed. Berkeley, CA: Nolo. Very useful for graduate students conducting long-term research related to science, biology, chemistry and technology. Discusses how to find patents in a variety of commercial databases as well as at the PTO and EPO. Provides important background information on patent eligibility and determining how to go about filing for a patent. Discusses how to optimize results by using keyword searches and understanding the patent classification system. Students may particularly enjoy the chapter discussing the pros and cons of using Google for patent searches. Katcher, Brian S. MEDLINE: A Guide to Effective Searching in PubMed and Other Interfaces. 2nd ed. San Francisco: Ashbury, 2006. -Katcher theorizes that once users have a better understanding of the history, theory, and purpose of Medline, they will become better critical thinkers and be able to adapt to the unique structure of that index to find meaningful results. Details about why Medline was created, the purpose of Medical Subject Headings (MeSH), record structures, and key tools, including related articles, clinical theories, and special theories, provide rich context for research and scope. The detailed guides discussing the differences between MeSH terms and Supplementary Concepts are very user-friendly. Once users better understand how Medline and PubMed work, they will efficiently be able to formulate stronger search strategies, use the right keywords, and link concepts to find the information they need.

Colon Cancer Guide 8 Review Rethlefsen, ML. (2007). MEDLINE: A Guide to Effective Searching in PubMed and Other Interfaces. Journal of the Medical Library Association. 95(2): 212213. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852622/ Volk, Ruti. (2007). The Medical Library Association Guide to Cancer Information: Authoritative, Patient-Friendly, Print and Electronic Resources. New York: Neal-Schuman Publishers. -Addresses a wide variety of readers, who may or may not be comfortable with medical terminology. The second part of the book specifically deals with 35 types of cancer, including colon and rectal cancers, and discusses incidence data from the US. Volk also discusses potential environment factors that may play a role in cancer cell development. The third section touches upon prevention and making healthy lifestyle choices. Volk specifically addresses prevention tips for individuals who may have a genetic predisposition. Review Felber SH (2008). The Medical Library Association Guide to Cancer Information: Authoritative, Patient-Friendly Print, and Electronic Resources. Journal of the Medical Library Association; 96(2): 172-173. doi: 10.3163/1536-5050.96.2.173 Conferences: Conferences allow doctors, activists, and researchers from across the world to come together and learn about new research and treatment methods. While there are many general conferences focusing on cancer, the conferences below specifically deal with FAP or Lynch Syndrome cases of inherited colon cancer and are sponsored by authoritative organizations, medical groups, and/or government associations. Recent Conferences and their Proceedings: National Institute of Health State of the Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening. February 2-4, 2010 in Bethesda Maryland. http://consensus.nih.gov/2010/colorectal.htm The National Institute of health holds annual conferences on a variety of medical topics. The 2010 conference solely focused on colon cancer. At this point in time, the organization is unsure of when they will hold another colon cancer conference. Conference proceedings from the last conference are available here: http://consensus.nih.gov/2010/docs/CRC%20SOS%202010%20Final%20Panel%20State ment.pdf -This link contains programs and abstracts, archived videos from all 3 days of conference proceedings, evidence reports, planning committee documents, panel sponsors, agendas, and the cohesive final statement. The AACR Colorectal Cancer Conference: Biology to Therapy conference was held in Philadelphia, Pennsylvania at the Loews Hotel from October 27-30, 2010. The conference was chaired by Anil K. Rustgi (Abramson Cancer Center, University of Pennsylvania), Joanna L. Groden (Ohio State University College of Medicine), and Richard M. Goldberg (University of North Carolina, Chapel Hill). Full conference proceedings are available for purchased for

Colon Cancer Guide 9 $40; however the final program, media highlights, and abstracts from the poster session are freely available on line. The conference was international in scope, focusing on stem cell and regenerative biology, regulation of the genome, genetics of susceptibility, inflammation and the tumor microenvironment, advances in diagnostics, mouse models, and clinical trials/experimental therapeutics. Many emerging treatments show promise, including a new DNA methylation test that may change the way screening procedures occur. The American Association of cancer research hosts an annual conference, as well as multiple, specifically-focused conferences throughout the year. The next special conference that may be of interest would be Cancer Susceptibility and Cancer Susceptibility Syndromes which will be held in Winter 2014. The ACCR webpage will make announcements as a definite location and time are decided upon for the next conferece. For more information, see the link below: http://www.aacr.org/home/scientists/meetings--workshops/meetings--workshopscalendar.aspx The African American Outreach Committee of the American Cancer Society hosted Colon CancerIts Preventable on Saturday, April 21st 2011 in Riverside, California. Important speakers include the president of the American Cancer Society, Clifford Eke MD, who spoke about colon and prostate cancers and Dave Williams MD, from the Center for Lifestyle Medicine, spoke about the relationship between genetics and nutrition in preventing and treating cancers. According to the committee, more than half of total deaths from colon cancer could have been prevented if they were regularly screened. Low income populations, especially those without health insurance, and African Americans have higher mortality rates than any other population. More than 90% of colon cancer cases occur in individuals over 50, so the American Cancer Society recommends preventive screening to everyone over 50 and younger individuals who have a family history of the disease. To read the proceedings from the conference and more statistics, visit the link below: http://www.cancer.org/myacs/California/areahighlights/african-american-colonhealth-conference Upcoming Conferences Genes & Cancer Meeting at the University of Warwick in Coventry, England December 10-12th, 2012 (29th annual meeting) http://www.genesandcancer.org.uk/ At this point in time, a formal syllabus has not been established, however the website will be updated when more information and speakers and topics have been decided upon. Sponsored by Institute of Cancer Research. http://www.icr.ac.uk/ Cancer Genetics & Epigenetics Gordon Conference April 21-26, 2013 Renaissance Tuscany Il Ciocco Resort at Lucca (Barga), Italy The esteemed Gordon Conferences are well-known in the scientific community as places for innovation and collaboration of scholarly research. Applications to attend the Cancer Genetics & Epigenetics conference in 2013 are due by March 24, 2013, but individuals are urged to apply as soon as possible, since space may fill up before the deadlines. A preliminary program, including speakers and topics for various sessions, will be available online by July 1, 2012 here: http://www.grc.org/programs.aspx?year=2013&program=cancgen. Interested users can sign up for RSS updates at this site to ensure they will be updated immediately as information continues to develop.

Colon Cancer Guide 10 To learn more about the scope and the history of Gordon Conferences, read the official conference statement from conference chair Joseph F. Costello and Vice Chair Ricky Johnstone here: http://www.grc.org/programs.aspx?year=2013&program=cancgen. Redefining Colorectal Cancer Survivorship: Live Your Best Life. July 20-21, 2012 at Renaissance Baltimore Harborplace Hotel Baltimore, Maryland -This conference, organized by the Colon Cancer Alliance, is the organizations National 2012 Conference intended to connect healthcare professionals, researchers, advocates, patients, and survivors of colon cancer. From the conference homepage, http://www.ccalliance.org/nationalconference/index.html, users can view the program agenda, conference registration, speakers, learning objectives, resources materials, and financial information. The conference will feature a symposium dedicated to the rising trend of colon cancers in individuals under 50 that will discuss hereditary/inherited causes. The 16th Annual Meeting of the CGA-ICC,( collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) on October 27-29, Boston, MA at the Sheraton Boston. This conference is directly after the National Society of Genetic Counselors 2012 Annual Education Conference, also in Boston, from October 24-27th, to encourage collaboration and communication between these two groups. The CGA-ICC conference was developed to allow for clinicians, scientists, and researches to collaborate on new developments in prevention, diagnosis, and treatment of patients and families with hereditary colorectal cancer syndromes. This conference is specifically aimed to practicing professional nurses, geneticists, genetic counselors, gastroenterologists, medical oncologists, colorectal surgeons, and psychologists. Students wishing to attend should contact the organization (contact information listed on the next page under the organization section). The program, including a syllabus and list of objectives, is posted online here: http://www.cgaicc.com/Meetings/2012AnnualMeeting.aspx The conference papers, programs, and proceedings will be freely available online 60 days after the conference. Organizations: A wide variety of organizations are decided to colon cancer research, diagnosis, treatment, and discovery. The following organizations are those that are intended for students, researchers, and medical professionals wishing to learn and share information about hereditary and environmental causes, diagnoses, and treatments of/for colon cancer. All available contact information is provided.

Colon Cancer Guide 11 The Collaborative Group of the Americas on Inherited Colorectal Cancer To learn more, contact: CGA Administrative Director: Dr. James Church Director, David G. Jagelman Colorectal Cancer Registries Cleveland Clinic Foundation Department of Colorectal Surgery 9500 Euclid Avenue, Desk A30 Cleveland OH 44195 Office: (216) 444-3540 President of the CGA, 2011-2012: Carol A. Burke, MD Director, Center for Colon Polyps & Cancer, Department of Gastroenterology Cleveland Clinic Foundation Department of Gastroenterology and Hepatology 9500 Euclid Avenue, Mail code A-30 Cleveland OH 44195 Office: (216) 444-6536 American Association for Cancer Research 615 Chestnut St., 17th Floor Philadelphia, PA 19106-4404 Telephone: (215) 440-9300 Toll Free Telephone: 1-866-423-3965 Fax: (215) 440-9313 Email: aacr@aacr.org -The Collaborative Group of the Americas on Inherited Colorectal Cancer was founded in 1995 to improve research and understandings of inherited colorectal cancer. The organization specifically focuses on family with identified forms including: -Familial Adenomatous Polyposis (FAP) - Peutz-Jeghers syndrome -Juvenile Polyposis/Hamartomatous Polyposes -Hereditary Non-Polyposis Colorectal Cancer (HNPCC) -Lynch syndrome - Hyperplastic Polyposis/Serrated Polyposis To read this organizations detailed mission statement, please visit The Collaborative Group of the Americas on Inherited Colorectal Cancer available at: http://www.cgaicc.com/

The AACR accelerates progress toward the prevention and cure of cancer by promoting research, education, communication, and collaboration..The programs and services of the AACR foster the exchange of knowledge and new ideas among scientists dedicated to cancer research, provide training opportunities for the next generation of cancer researchers, and increase public understanding of cancer. Continuing reading AACR: About Us here http://www.aacr.org/home/about-us.aspx Publishes: Cancer Today, Cancer Research, Clinical Cancer Research, Molecular Cancer Therapeutics, Molecular cancer research, Cancer Epidemiology, Biomarkers & Prevention and Cancer Prevention Research.

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American Society of Colon and Rectal Surgeons 85 W. Algonquin Rd., Suite 550 Arlington Heights, IL 60005 Phone: 847-290-9184 Fax: 847-290-9203 Email: ascrs@fascrs.org http://www.fascrs.org/

The American Society of Colon and Rectal Surgeons (ASCRS) is the premier society for colon and rectal surgeons and other surgeons dedicated to advancing and promoting the science and practice of the treatment of patients with diseases and disorders affecting the colon, rectum and anusThe American Society of Colon and Rectal Surgeons is the recognized authority on conditions and diseases of the colon, rectum and anus. To finish reading this article, please visit: http://www.fascrs.org/ Upcoming ASCRS Annual Meeting June2-6 2010 at the Henry B. Gonzalez Convention Center, San Antonio, Texas. To learn more about the annual conference, please visit: http://www.fascrs.org/annual_meeting/

National Cancer Institute at the National Institutes of Health. Call 1-800-4-CANCER A trained Cancer Information Specialist is available to answer your questions. The NCI's LiveHelp online chat service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. NCI Public Inquiries Office Suite 3036A 6116 Executive Boulevard, MSC8322 Bethesda, MD 20892-8322

The National Cancer Institute (NCI) is part of the National Institutes of Health (NIH), which is one of 11 agencies that compose the Department of Health and Human Services (HHS). The NCI, established under the National Cancer Institute Act of 1937, is the Federal Government's principal agency for cancer research and training.To finish reading the article, please visit http://www.cancer.gov/cancertopics/pdq/genetics/colo rectal/HealthProfessional/page1/AllPages This organization provides very detailed information concerning colon cancer genes, genetic polymorphisms, colorectal cancer risk, major genetic syndromes, and Psychological Issues in Hereditary Colon Cancer Syndromes (Lynch Syndrome and Familial Adenomatous Polyposis).

Hereditary Cancer Institute Creighton University School of Medicine Preventive Medicine 2500 California Plaza Omaha, NE 68178 Phone: (800) 648-8133

The HCCs is devoted to cancer prevention resulting from identification of hereditary cancer syndromes with particular attention given to surveillance and management programs melded to the natural history of these particular hereditary disorders. HCC has accumulated a Registry of 1743 families with over 30,000 patients at riskThe HCC commitment has continued since its inauguration and has now evolved significantly into the molecular genetic age where germline mutations have been found in countless cancer

Colon Cancer Guide 13 prone kindreds with particular emphasis in the hereditary breast ovarian cancer syndrome, the familial typical multiple mole melanoma (FAMMM) syndrome in association with pancreatic cancer and the hereditary nonpolyposis colorectal cancer (HNPCC) syndromes, also referred to as the Lynch syndrome. To finish reading this description, please visit: http://medschool.creighton.edu/medicine/centers/hcc /index.php Indexes and Abstracting Services Particularly useful biomedical databases with indexing and abstracting services, including Medline/Pub Med, Embase, Bisosis, Web of Science, Chem Abstracts, Nursing & Allied Health and Cancer Lit, will be discussed. Medline: Medline is produced by the US National Library of Medicine, which also provides a similar, free version called PubMed. This database focuses specifically on medical research and technologies, including biology sciences, allied health, nursing, healthcare, medicine, genetic disorders and more. Medline has citations from over 4,600 national and international biomedical journals. This is the primary research tool to begin research of any medical related topic. Medline uses the NLMs Medical Subject Headings (MeSH) as a system of controlled vocabulary for indexing. It is extremely important to take the time to plan a search strategy for success; natural language and commercial drug names will not help you in this database. MeSH vocabulary provides uniformity, ensuring that articles about the same topic described in differing words are indexed together under a uniform heading. MeSH headings can be linked with MeSH subheadings, which are broad concepts such as diagnosis, therapy, research etc. The average article will have between 5 and 15 terms indexed as key words to cover the full scope of that article. It is important to note, unlike google, Medline does not index every word in the article; this is why choosing the right key words are crucial. When viewing a result article, the key terms with an asterisk* have been chosen, by the indexer, as the most relevant and main focuses of that publication. To learn more, visit the official Medline/Pub Med research guide from the US National Library of Medicine here: http://www.nlm.nih.gov/bsd/pmresources.html Embase: This database covers preclinical and life sciences. Embase will only provide results from 1990 to the present, which is actually a benefit for this particular topic since genetic research

Colon Cancer Guide 14 related to inherited forms of colorectal cancer did not become prominent until after 1990. Relevant topics of interest here include biology, biochemistry, cell biology, medical sciences, genetics, and molecular biology. Embase contains abstracts and citations to over 4,000 biomedical publications. Embase has its own thesaurus, EMTREE. This is very helpful in that EMTREE offers crossreferences from a word you choose to a synonym that is the preferred term/controlled vocabulary of the database. The system uses natural order words (not to be confused with natural language1) rather than inverted order (ex: Lung tuberculosis, not tuberculosis, lung). Embase requires that you avoid acronyms, abbreviation, and, in most cases, punctuation. The OVID interface here will look almost identical to that of Medline, however once you choose a keyword and map term to subject heading you will see that the controlled vocabulary here is significant different. Both Medline and Embase recognize colorectal neoplasms as a search for colon cancer. Searching colon cancer will not provide you with optimal results. If questioning which recommended term best suits your topic, view the scope note available for any of the accepted headings. To learn more, visit Embases official website at: http://www.embase.com/info/what-embase Biosis: Covers international research and publications related to biology and biomedical sciences. Highlights include citations from Biological Abstracts and Biological Abstracts Reports, Reviews, and meetings. Citations come from approximately 5,000 journals and monographs. Selected reports and specific book chapters are also included. US patents from 1994 to the present related to biology and biomedical sciences can be found here. The indexing in Biosis is more broad than in Medline. Biosis, like Embase, provides helpful scope notes that allow you to explore topics if you are unsure of where your specific information need falls. Similar content will be found in Medline and Embase. Chem Abstracts: Includes over 20 million citations involving chemical topics. Coverage ranges from 1967-present. The CAS (chemical abstracts service) uses their own system of indexing. Controlled vocabulary can be identified by examining the CA General Subject Index Headings. Molecular chemicals are given CAS Registry Numbers, which are uniquely assigned to each chemical compound. Citations from journal articles, patents, reviews, technical reports, conference proceedings, dissertations, and book are included. Topics relevant to hereditary colorectal cancer include applied chemistry, biochemistry and biology, pharmaceuticals, radiation chemistry, toxicology, macromolecular chemistry, and organic chemistry. This is the place to look to learn more about specific genes, treatment technologies, and medicines discussed in patents. Web of Science: Contains a very useful citation index for social sciences and a wide range of life sciences. Web of Science does not have its own formal indexing language or thesaurus. Instead, you

Colon Cancer Guide 15 should try to create searches that encompass all possible synonyms for your topic. The cited author tool is particularly useful for tracing important people in a particular industry. Over 6,000 science journals are indexed with complete bibliographic data. The follow tutorial is useful for those who have never encountered this database: http://science.thomsonreuters.com/tutorials/wos7/ Cancer Lit: is a product of the US National Cancer Institute. This database contains citations, mostly with abstracts, related to all aspects of cancer causes, diagnosis, therapy, biochemistry, mutagens, and genetics of inherited forms of cancer and of cancer cells general behaviors. Most of the records come from a core of 200 journals, which overlaps with coverage from MEDLINE. Government reports, meeting proceedings, monographs, and symposium reports for some topics are included. Libraries of Importance: The National Cancer Institute, a department of the National Institutes of Health, has an extensive online library with freely available electronic resources and journals. Surprisingly, a significant portion of the materials are written at a very high-level, assuming readers have experience with biology, MeSH language, or genetics. The library includes reference materials, NCI publications, resources in Spanish, and significant government reports from the NCI. This resource can be accessed here: http://www.cancer.gov/cancertopics/cancerlibrary The National Library of Medicine has a network to connect with medical libraries from around the country. The Middle Atlantic Region services New Jersey, Pennsylvania, Delaware, and New York. In New Jersey, University of Medicine and Dentistry of New Jersey (located in Newark) is highlighted for their medical collection. Because this University is supported by New Jersey tax dollars, members of the public can come into the Smith Library and use one of the 48 public access workstations or use any of the print materials (which cannot be checked out). Due to the mergers occurring in New Jersey Higher Education, the Reuben L. Sharp Library of the Health Services (from the Cooper Health System) has become a member of the UMDNJ library system and has incorporated more works into their collection. To explore electronic and print collections, please visit: http://libraries.umdnj.edu/newarklib/index1.html New York has many Medical Schools and University Libraries with medical resources. Specifically renown schools include Albert Einstein College of Medicine (Bronx, NY), Columbia

Colon Cancer Guide 16 University (NY, NY), Memorial Sloan-Kettering Cancer Center (NY,NY), Roswell Park Cancer Institute (Buffalo, NY), and Weill Medical College of Cornell University (NY, NY). The University catalogs are available online for searching. The libraries in Hospitals and Research Centers may be available to scholars if they contact the library. Links to Library webpages with contact information are below: -Cornell University Weil Medical Center: http://library.med.cornell.edu/ -Rowell Park Cancer Institute: http://www.roswellpark.org/ -Albert Einstein College of Medicines D. Samuel Gottsesman Library: http://library.einstein.yu.edu/ -Columbia University August C Longs medical Library: restricted, not public access to nonUniversity students from off campus internet collections. Visitors can make appointments to visit the physical library and use resources there. -Memorial Sloan-Kettering Cancer Center Library: http://library.mskcc.org/scripts/portal/index.pl Reviews: Reading prominent review articles will provide you with context about the history of the field and the important people and places. The following reviews were frequently cited by other medical researchers and come from esteemed, well-established medical journals. Recommended review articles are cited below. Choong MK. Tsafnat G. (2012). Genetic and epigenetic biomarkers of colorectal cancer. [Review] Clinical Gastroenterology & Hepatology. 10(1):9-15. UI: 21635968. (New article: number of times cited not yet available) Chung DC. (2000). The Genetic basis of Colorectal Cancer: Insights into Critical Pathways of Tumorigenesis.: GASTROENTEROLOGY, 199(3):: 854-865. DOI: 10.1053/gast.2000.16507 Times Cited: 219 Fodde R, Smits R, and Clevers H. (2001). APC, signal transduction and genetic instability in colorectal cancer. NATURE REVIEWS CANCER Volume 1(1): 55-67. DOI: 10.1038/35094067 Published: OCT 2001 Times Cited: 366 Johns LE and Houlston RS. (2001). A systematic review and meta-analysis of familial colorectal cancer risk. AMERICAN JOURNAL OF GASTROENTEROLOGY, 96(10): 2992-3003 DOI: 10.1111/j.1572-0241.2001.04677.x Times Cited: 220 Robbins DH, Itzkowitz SH, and Janowitz HD. (2002). The molecular and genetic basis of colon cancer. Medical clinics of North America (United States ) , 86 (6) p1467-95. Times Cited: 33

Colon Cancer Guide 17 Rowley P.T. (2005). Inherited susceptibility colorectal cancer. Annual Review of Medicine (United States), 56:(539-554). DOI: 10.1146/annurev.med.56.061704.135235 Times Cited: 41 Shen YM. Arbman G. Sandstrom P. Gullstrand P. Wei YQ. Zhang H. Rosell J. Olsson B. Peng F. Yang HS. Wang CT. Sun XF. (2012). Novel gene hBiot2 is an independent prognostic factor in colorectal cancer patients. Oncology Reports. 27(2):376-82. UI: 22024937 (New article: number of times cited not yet available) Vogelstein B and Kinzler KW. (2004). Cancer genes and the pathways they control. NATURE MEDICINE , 10(8): 789-799. DOI: 10.1038/nm1087 Times Cited: 1,346 (from Web of Science) Prominent review journals, such as Nature Reviews Genetics, Nature Reviews Clinical Oncology, and Nature Reviews Cancer will be discussed in the forthcoming Journal section of this libguide. Patents There are many different types of patents related to colon cancer, covering equipment, screening procedures, gene-related theories and testing, etc. While hereditary colon cancer genes have been patented, they are nonexclusively licensed. This allows for further research and developments in patient care, which is the ultimate purpose of genetic research. I will specifically highlight patents related to genes involved in colon cancer. For more information on colon cancer treatments and screening, visit the site below: http://www.uspto.gov/patft/help/ftman.pdf A useful guide for completing advance patent searching can be found here: http://patft1.uspto.gov Patent Number & Name 8,153,380 Gene expression markers for colorectal cancer prognosis Some of the Many Inherited Colon Cancer Patents include: Sponsors & Inventors Class Abstracts Assignees Genomic Health, Inc. (Redwood City, CA) NSABP Foundation, Inc. (Pittsburgh, PA) Genomic Health, Inc. (Redwood City, CA) NSABP Watson; Drew Paik; Soonmyung Cowens; Wayne Baker; Joffre B. Clark; Kim Hackett; James 435/6.14 ; 435/6.12 A method of predicting clinical outcome in a subject diagnosed with colorectal cancer comprising determining evidence of the expression of one or more predictive RNA transcripts or their expression products in a biological sample of cancer cells obtained from the subject. A method of predicting clinical outcome in a subject diagnosed with colorectal cancer comprising determining evidence of the expression of one or more predictive

8,153,379 Gene expression markers for colorectal

Watson; Drew Paik; Soonmyung Cowens; Wayne Baker; Joffre B. Clark; Kim Hackett;

435/6.14 ; 435/6.12

Colon Cancer Guide 18 cancer prognosis Foundation, Inc. (Pittsburgh, PA The Johns Hopkins University (Baltimore, MD) James RNA transcripts or their expression products in a biological sample of cancer cells obtained from the subject. 435/4 ; 435/40.5; 530/350 The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells. A method of predicting clinical outcome in a subject diagnosed with colorectal cancer comprising determining evidence of the expression of one or more predictive RNA transcripts or their expression products in a biological sample of cancer cells obtained from the subject.

de la Chapelle; Albert FI, Vogelstein; Bert Kinzler; Kenneth W.

5,837,443 Diagnostic method employing MSH2 protein

8,153,378 Gene expression markers for colorectal cancer prognosis

Genomic Health, Inc. (Redwood City, CA) NSABP Foundations, Inc. (Pittsburgh, PA) Genomic Health, Inc. (Redwood City, CA) NSABP Foundation, Inc. (Pittsburgh, PA) Genomic Health, Inc. (Redwood City, CA) NSABP Foundation, Inc. (Pittsburgh, PA)

Cowens; Wayne (Tiburon, CA), Baker; Joffre B. (Montara, CA), Clark; Kim (Sunnyvale, CA), Hackett; James (San Jose, CA), Watson; Drew (Los Altos, CA), Paik; Soonmyung (Pittsburgh, PA) Watson; Drew Paik; Soonmyung Cowens; Wayne Baker; Joffre B. Clark; Kim Hackett; James

435/6.14 ; 435/6.12

8,029,995 Gene expression markers for colorectal cancer prognosis 8,026,060 Gene expression markers for colorectal cancer prognosis

435/6.14 ; 435/91.2

A method of predicting clinical outcome in a subject diagnosed with colorectal cancer comprising determining evidence of the expression of one or more predictive RNA transcripts or their expression products in a biological sample of cancer cells obtained from the subject. A method of predicting clinical outcome in a subject diagnosed with colorectal cancer comprising determining evidence of the expression of one or more predictive RNA transcripts or their expression products in a biological sample of cancer cells obtained from the subject.

Watson; Drew Paik; Soonmyung Cowens; Wayne Baker; Joffre B. Clark; Kim Hackett; James

435/6.12 ; 435/6.14; 435/91.2

Colon Cancer Guide 19 Assignees The Johns Hopkins University (Baltimore, MD) The University of Utah (Salt Lake City, UT) The Cancer Institute (Tokyo, JP) Zeneca Limited (London, GB) diaDexus, Inc. (So. San Francisco, CA) -Vogelstein Bert KinzlerKenne h W. Albertsen; HansAnand; Rakesh (Chelford, GB), Carlson; Mary Groden; Joanna Hedge; Philip John Joslyn; Geoff Markham; Alexander Fred Nakamura; Yusuka Thilveris; Andrew White A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.

7,718,787 Gene families associated with cancers

536/23.5 ; 435/320.1 ; 435/325; 435/455; 435/69.1

7,022,472 Mutations in human MLH1 and human MSH2 genes useful in diagnosing colorectal cancer 7,326,778 Mutator gene and hereditary nonpolyposis colorectal cancer

Robbins; David (Stevenson Ranch, CA), Lin-Goerke; Juili Lillian (Spring City, PA), Ling; Jessica C. (Bensalem, PA)

435/6.12 ; 536/23.1; 536/24.3

Assignees The John Hopkins University (Baltimore, MD)

de la Chapelle; Albert (Helsingfors, FI), Vogelstein; Bert (Baltimore, MD), Kinzler; Kenneth W. (Baltimore, MD)

536/23.1

6,448,041 Colon Cancer Marker

Incyte Genomics, Inc. (Palo Alto, CA)

Wolven; Amy K. (Oakland, CA), Krasnow; Randi E. (Stanford, CA), Warren; Bridget A. (Cupertino, CA),

435/69.1 ; 435/320.1 ; 435/325; 435/70.1; 536/23.1; 536/23.5

Variant human MLH1 and MSH2 genes are provided. Methods of using these variant genes to diagnose hereditary non-polyposis colorectal cancer (HNPCC) and/or determine a patient's susceptibility to developing HNPCC are also provided. Methods and compositions for identifying new variant MLH1 of MSH2 genes are also provided. In addition, experimental models for hereditary non-polyposis colorectal cancer comprising these variant genes are provided. The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells. The invention provides a cDNA which encodes a colon cancer marker. It also provides for the use of the cDNA, fragments, complements, and variants thereof and of the encoded protein, portions thereof and antibodies

Colon Cancer Guide 20 Baughn; Mariah R. (San Leandro, CA) thereto for diagnosis and treatment of colon disorders, particularly colon cancer and polyps. The invention additionally provides expression vectors and host cells for the production of the protein and a transgenic model system. A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.

6,413,727 Diagnosis for mutant APC by immunoass ay

The Johns Hopkins University (Baltimore, MD) University of Utah (Salt Lake City, UT) Japanese Foundation for Cancer Research Cancer Institute (Tokyo, JP) Zeneca Limited (Chesire, GB) The Johns Hopkins University (Baltimore, MD) The University of Utah (Salt Lake City, UT) Zeneca Pharmaceutic als (GB2) The Cancer Institute (Tokyo, JP)

5,783,666 APC (adenomat ous polyosis coli) protein

Albertsen; Hans (Salt Lake City, UT), Anand; Rakesh (Sandbach, GB), Carlson; Mary (Salt Lake City, UT), Groden; Joanna (Salt Lake City, UT), Hedge; Philip John (Winsford, GB), Joslyn; Geoff (Salt Lake City, UT), Kinzler; Kenneth (Baltimore, MD), Markham; Alexander Fred (Crewe, GB), Nakamura; Yusuke (Tokyo, JP), Thliveris; Andrew (Salt Lake City, UT), Vogelstein; Bert (Baltimore, MD), White; Raymond L. (Salt Lake City, UT) -Albertsen; Hans Anand; Rakesh (Sandbach, GB2), Carlson; - Mary Groden; - Joanna Hedge; -Philip John (Winsford, GB2), Joslyn; Geoff -Kinzler; Kenneth Markham; Alexander Fred (Crewe, GB2), -Nakamura; Yusuke -Thliveris; Andrew -Vogelstein,Bert White, Raymond L.

435/7.23 ; 435/7.25; 436/501; 436/64; 436/66; 530/387.7

530/350 ; 530/828; 930/10

A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.

Patent information derived from: http://www.uspto.gov/web/patents/ of the United States Patents and Trade Mark Office. Relevant Patent Classes: Class 260: Chemistry: of Carbon Compounds

Colon Cancer Guide 21 Class 424: Drug, bio-affecting and body treating compositions Class 435: Chemistry: Molecular Biology and Microbiology Class 530: Chemistry: Natural Resins of Derivatives; Peptides or Proteins; Lignins or Reaction Products Class 530: Peptide or Protein Sequence Class 930: Peptide or Protein Sequence People of note in the field Albert de la Chapelle, MD, PhD Henry Lynch, MD Professor, Department of Molecular Virology, Chair of Preventive Medicine: Immunology and Medical Genetics Creighton University School of Medicine, 804 Biomedical Research Tower Omaha, NE 68178, USA. 460 W 12th Ave Columbus, OH 43210 Email: htlynch@creighton.edu Homepage: Email: albert.delachapelle@osumc.edu http://medschool.creighton.edu/medicine/cent Homepage: ers/hcc/welcome/index.php http://www.cancergenetics.med.ohiostate.edu/2729.cfm Lynch Earns National Award for Lifetime Work in Hereditary Cancer http://bit.ly/NxnLsN Bert Vogelstein, MD Patrice Watson, PhD HHMI Investigator Statistician & Associate Professor John Hopkins University School of Medicene Room 589, Cancer Research Building 410-955-8878 410-955-0548 (Fax) Email: vogelbe@jhmi.edu Homepage: http://www.hopkinsmedicine.org/kimmel_can cer_center/experts/Laboratory_Scientists/deta il/6424146D144F331F200D784A751851DB/B ert_Vogelstein Pivi Peltomki MD, PhD Professor in Biomedical Cancer Research Department of Medical Genetics, Haartman Institute P. O. Box 63 (Haartmaninkatu 8) FI-00014 University of Helsinki, Finland Phone: 358-9-191 25092 Fax: 358-9-191 25105 Email: paivi.peltomaki@helsinki.fi Homepage: http://www.helsinki.fi/haartman/lgo Creighton University Medical Center Department of Preventive Medicine Hixson-Lied Science Building, Suite 202 Omaha, NE 68131 Phone: (402) 280-1452 Fax: 402.280.1734 Email: patrice@creighton.edu Annika Lindblom MD, PhD Professor of Medical Genetics/Cancer Genetics Department of Molecular Medicine and Surgery Karolinska Institutet SE-171 77 Stockholm, Sweden Phone: +46 8-524 800 00 Fax: +46 8-31 11 01 Email: Annika.Lindblom@ki.se Homepage: http://ki.se/ki/jsp/polopoly.jsp?l=en&d=22393 &a=12474

Colon Cancer Guide 22 Internet Resources: Causes, Inheritance: Colon cancer. (2012). DNA Learning Center. http://www.dnalc.org/view/973Causes-Inheritance-Colon-cancer.html -Visually stimulating slideshow with statistics and commentary from colon cancer researchers. The website highlights one of the main differences between hereditary colon cancer and nonhereditary colon cancer: inherited genetics will drastically lower the average age of which the person develops colon cancer. The average individual develops colon cancer at 67 years old, but families who carry the genetic mutation often develop cancer in their 30s and 40s. Discusses case studies in which young children develop colon cancer. Distinguishes the differences between FAP and HNPCC and the role of APC gene and tumor suppressor genes. Colorectal Cancer Detailed Guide. (2012). The American Cancer Society. http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/index -This page functions as a subject guide, offering multiple links under topics including what is colon cancer, risk factors, prevention, key statistics, diagnosis, survival rates by stage, and forms of treatment. The section entitled Whats new in colorectal cancer research and treatment provides news of various treatments and new genetic-related discoveries. Heredity and Cancer (2012). The American Cancer Society. http://www.cancer.org/Cancer/CancerCauses/GeneticsandCancer/heredity-and-cancer -Very succinct description of the differences between naturally or environmentally stimulated cancer cases and inherited forms of cancer, which are by far less common. In FAP, teenagers begin developing many colon polyps and over time, at least one of the polyps will come cancerous. This syndrome is caused by the APC gene. The article discusses the potential choice to surgically remove the colon before polyps become cancerous. The site also discusses HNPCC/Lynch Syndrome, which has a complex genetic relationship with other forms of cancer (including breast and stomach cancers) cause by mutations in the MLH1, MSH2, MSH6, PMS1, or PMS2 genes. Introduction to Hereditary Colon Cancer. (2012). John Hopkins Colon Cancer Center. http://www.hopkinscoloncancercenter.org/CMS/CMS_Page.aspx?CurrentUDV=59&CMS_Page_ID= 35D3F013-122F-40BB-B506-FDB0DDB30D53 -Discusses differences between sporadic (non-inherited) and inherited/familial forms of colon cancer. This site uniquely discusses APC I1307K, which is a gene mutation found in Jewish people with ancestors from Eastern Europe. While the normal risk of inherited colon cancer is less than 5%, the rate for this population group is between (18 and 30%). The site discusses in detail how John Hopkins is conducting research to better understand this mutation. What Causes Cancer? Genes vs. Environment . (2012). National Foundation for Cancer Research. http://www.nfcr.org/index.php/cancer-information/412-what-causes-cancer-genes-vsenvironment -Interesting synopsis of current research and the results of studies specifically analyzing genetic forms of common cancers. Discusses In the New England Journal of Medicine study, genes did play a significant role in breast, colorectal, and prostate cancers, contributing 27, 35, and 42 percent of the risk, respectively. But, according to the researchers, genes alone cannot be fully responsible for these relatively high risks, suggesting that there are still major holes in our current understanding of the genetics of cancer. This supports many of the previous journal articles and book which state that inherited colon cancer occurs in less than 5% of all cases.

Colon Cancer Guide 23 Government internet resources: Colon and Rectal Cancer. (2012). National Cancer Institute at the National Institutes of Health. http://www.cancer.gov/cancertopics/types/colon-and-rectal -Interactive and visually stimulating online version of What You Need to Know About Cancer of the Colon and Rectum, which covers risk factors, screening, symptoms, diagnosis, staging, treatment., rehabilitation, complementary medicine, and research. The site also provides a bibliography of links to clinical trials, screening, treatment, and statistics. A specific subsection Prevention, Genetics, Causes discusses current knowledge and ongoing clinical trials. Colorectal Cancer Statistics. (2012). Center for Disease Control and Prevention. http://www.cdc.gov/cancer/colorectal/statistics/index.htm -This quality government resource provides statistics by age, race, ethnicity and state. It also discusses growing trends (by gender). The CDC has detailed information about how they are working to limit the mortality of colon cancer by educating people of the importance of screening and working with the government to provide grants for cancer researchers. Familial Adenomatous Polyposis. (2012). Genetics Home Reference: from the National Library of Medicine. http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis -Defines key subject terms and synonyms. This site also provides links to genetic testing centers and encourages individuals who have had a young family member diagnosed with cancer to undergo genetic testing. Desmoid tumors, noncancerous growths, may be provoked when a surgeon removes the colon and can often regenerate after the colon is removed. FAP side effects can include noncancerous and cancerous tumors on the stomach, small intestines, and other tissues. The NLM also discusses autosomal recessive familial adenomatous polyposis, in which fewer than 100 polyps develop (in FAP hundreds of thousands of polyps can develop), because a different gene causes this syndrome. Learning About Colon Cancer. (2012). National Human Genome Research Institute. http://www.genome.gov/10000466 -This site covers current knowledge of the relationships between heredity and cancer, testing for hereditary colon cancer, current NHGRI clinical research on hereditary colon cancer, and recommended electronic resources. Currently, researchers are focusing on communicating risks to immigrants (specifically Mexican-Americans) and studying the need for education and counseling for persons undergoing genetic testing for hereditary colon cancer. Details the specific genes and chromosomes involved in FAP and HNPCC. The Genes, Environment and Health Initiative (GEI). (2012). National Human Genome Research Institute. http://www.genome.gov/19518663 -Discusses the Genes, Environment and Health Initiative that first began in February 2006. The initiative aims to support research to better understand the relationships between genetic and environmental interactions in cancer. The group is lead by the National Human Genome Research Institute (NHGRI) and the National Institute of Environmental Health Sciences (NIEHS). This page offers information about meetings and workshops, genetics resources, and recently updates news about results from clinical trials and gene mapping initiatives.

Colon Cancer Guide 24 Journals Examine this chart of prominent journals and pay careful attention to impact factors and scope notes. Then, consult the specific journal articles mentioned to gain a better understanding of the history of the field and current research focuses.

Journal Name
New England Journal of Medicine

Impact Score
53.486

ISSN
00284793

Ranking
#1 (out of 153) in MEDICINE, GENERAL & INTERNAL

Publisher
Massachuse tts Medical Society

Scope Notes
Prestigious, peer-reviewed journal of the medical sciences. Published weekly and includes original articles, book reviews, editorials, images, and more. Refereed journal focusing on news from fields of clinical and experimental oncology. Peer-reviewed journal published 6 times a year and is intended for medical professionals to learn about aspects of cancer diagnosis, treatment, and prevention. It has a circulation rate of about 84,000. Journal aims to support research to lead to higher prevention and survival rates. Focuses on genomic instability, cancer cell cycle, growth inhibitory signals, metastasis, cancer prevention, genomic vs. environmental triggers, experimental approaches, ethical, legal, and social issues, etc. Peer-reviewed, weekly medical journal established in 1883. Has original research, reviews, editorials, news, correspondence and more focusing on medical and biological sciences. Issues of public health and nonclinical aspects of medicine are also discussed. Published monthly, this oncology journal is useful for

Journal of Cancer Research and Clinical Oncology A Cancer Journal for Clinicians

2.485

01715216 00079235

#92 (out of 185) in Oncology #1 (out of 185) in Oncology

Springer

94.333

WileyBlackwell

Nature Reviews Cancer

37.184

1474175X

#2 (out of 185) in Oncology

Nature Publishing Group

JAMA

30.011

00987484

#3 (out of 153) in Medicine, General & Internal

American Medical Association

Cancer Cell

25.430

15356108

#3 (out of 178) in Cell Biology

Cell Press

Colon Cancer Guide 25 #3 (out of 185) in Oncology Nature Medicine 25.430 10788956 Ranked #3 (out of 286) in Biochemistry & Molecular Biology -Ranked 5th (out of 178) in Cell Biology -#1 (out of 106) in Medicine, Research & Experimental Ranked #4 (out of 185) in Oncology Nature Publishing Group studies of cancer cell cycles and mutations. Biomedical research journal intended for scientists and physicians. Covers cancer biology, gene theory, immunology, and more.

Journal of Clinical Oncology

18.970

0732183X

American Society of Clinical Oncology

Lancet Oncology

17.764

14702045

#5 (out of 185) in Oncology

Elsevier Science INC.

Peer-reviewed journal published 3 times a month that is intended for physicians and cancer specialists and focuses on caring for patients with cancer and treatment options. Published monthly and focuses on original research, reviews, commentaries, and news from international contributors related to oncology research. This journal should be consulted for news, studies, and innovative ideas related to better understanding how cancer develops, treatment models, and prevention. Focuses on practices and providing professional support for practicing clinicians in the fields of gastroenterology disorders. Very useful for information about the colon, small bowel, and pathology. International focus targeting researchers and academic institutions (more so than practicing clinicians looking for practical advice). Assumes audiences have a high level of knowledge in oncology. Regularly covers

Journal of the National Cancer Institute

14.697

00278874

#6 (out of 185) in Oncology

Oxford University Press

American Journal of Gastroenterolog y

26.386

00029270

#5 (out of 72) in GASTROENTEROLOGY & HEPATOLOGY

Nature Publishing Group

Nature Reviews Clinical Oncology

10.787

17594774

#7 (out of 185) in Oncology

Nature Publishing Group

Colon Cancer Guide 26 chemotherapy, clinical pharmacology, diagnosis, epidemiology, experimental theories, hormonal therapies, medical oncology, prevention, radiotherapy, and surgical oncology. Important resource to keep up with genetic resources and dsicoveries related to genomics, genome sequencing, cancer geonomics, bioinformatics, evolutionary genetics, population genetics, new technologies and techniques, therapy, applied genetics, computational biology, gene expression, gene profiling, disease gene identification, chromosome biology, epigenetics, etc. Peer-reviewed journal focusing on molecular biology, cell biology, and biochemistry of cells and confronts controversial issues with scholarship. Relatively new journal, created in 1995, that publishes peer-reviewed, international articles on genome biology and advances in genomic medicine. Focuses include genome structure, molecular evolution, population genetics, computational biology, and epigenetics. Often provides complete data sets if readers request more data from a research article. Monthly referred journal focusing on updates about new mutations and clinical implications of original mutation research. Ultimate goal is to foster

Nature Reviews Genetics

32.745

14710056

#2 (out of 156) in Genetics & Heredity

Nature Publishing Group

Oncogene

7.414

09509232

Genome Research

15.588

10889051

-#15 (out of 185) in Oncology -#14 (out of 156) in Genetics & Heredity -#34 (out of 286) in Biochemistry & Molecular Biology -#8 (out of 286) in Biochemistry & molecular Biology -#3 (out of 160) in Biotechnology & Applied Microbiology -#6 (out of 156) in Genetics & Heredity

Nature Publishing Group

Cold Spring Harbor Lab Press

Human Mutation

5.956

10597794

#18 (out of 156) in Genetics & Heredity

WileyBlackwell

Colon Cancer Guide 27 understanding of human genome and genetic disorders to improve health care. Targeted for molecular and medical geneticists researching in academic or industrial settings and practicing clinicians. Published twice a month to showcase original studies, reviews, and editorials. Intended for those doing epidemiological research or clinical work. Subsections include molecular and cellular pathobiology, tumor and stem cell biology, micro environment and immunology, therapeutics ,epidemiology, prevention, and medical roles and implications of technology. Highly selective, international journal for original research related to human genetics. Discusses roles and behaviors of genetics in diseases, cancer genetics, clinical manifestations of genetic disorders, molecular genetics, and evaluation of experimental therapies. Peer-reviewed journal focusing on increasing knowledge and understanding of causes and paths of cancer. Investigates new therapies, molecular properties relevant to cancer diagnosis and treatment. Aim for both medical professionals and individuals interested in learning more about oncology. Publishes research, methodological developments and epidemiological research. Discusses social, political,

Cancer Research

8.234

00085472

#12 (out of 185) in Oncology

American Association of Cancer Research

Journal of 7.037 Medical Genetics

00222593

#16 out of 156 Genetics & Heredity

BMJ Publishing Group

British Journal of Cancer

4.831

00070920

#136 (out of 185) in Oncology

Nature Publishing Group

American Journal of Epidemiology

5.745

00029262

36 (out of 142) in Public, Environmental & Occupational Health

Oxford University Press INC.

Colon Cancer Guide 28 and economic implications of information. Aimed at epidemiologists and clinicians and public health care workers who use epidemiological data. This biomedical journal focuses specifically on human genetics and how gaining a better understanding of genetics and DNA processes with lead to improvements in internal medicine, and molecular medicine. Specific areas of focus include genetic structure and expressions, mutation detection, physical mapping, molecular diagnostics, genetic epidemiology, genotype/phenotype relationships, molecular genetics of tumorigenesis and more.

Human Genetics

5.047

03406717

#23 (out of 156) in Genetics & Heredity

Springer

Journal information derived from: Journal Citation Reports: JCR Science Edition. (2010). Thompson Reuters. http://adminapps.webofknowledge.com.proxy.libraries.rutgers.edu/JCR/JCR?RQ=HOME Ulrich's Periodicals Directory (2012). Serial Solutions: A Proquest Company. http://ulrichsweb.serialssolutions.com.proxy.libraries.rutgers.edu/ Influential Articles (in order of the most influential/most cited): AALTONEN LA; PELTOMAKI P; LEACH FS; et al. (1993). Clues to the Pathogenesis of Familial Colorectal-Cancer. SCIENCE, 260(5109): 812-816. DOI: 10.1126/science.8484121 Published: MAY 7 1993 Times Cited: 2,232 FISHEL R; LESCOE MK; RAO MRS; et al. (1993). The Human Mutator Gene Homolog MSH2 and its Association with Hereditary Nonpolyposis Colon-Cancer. CELL, 75(5), 1027-1038. DOI: 10.1016/0092-8674(93)90546-3 Times Cited: 2,087 BRONNER CE; BAKER SM; MORRISON PT; et al. (1994). Mutation in the DNA Mismatch Repair

Colon Cancer Guide 29 Gene Homolog HMLH1 is Associated with hereditary Nonpolyposis Colon-Cancer. NATURE, 368(6468): 258-261 DOI: 10.1038/368258a0 Times Cited: 1,574 (from Web of Science) Vogelstein B and Kinzler KW. Cancer genes and the pathways they control. NATURE MEDICINE, 10(8): 789-799 DOI: 10.1038/nm1087 Published: AUG 2004 Times Cited: 1,346 (from Web of Science) Lichtenstein P; Holm NV; Verkasalo PK; et al. (2000). Environmental and hereitable factors in the causation of cancer-Analyses of chorts of twins from Sweden, Denmark, and Finland. NEW ENGLAND JOURNAL OF MEDICINE, 343(2): Volume: 78-85. DOI: 10.1056/NEJM200007133430201 Times Cited: 1,304 (from Web of Science) Vasen HFA; Watson P; Mecklin JP; et al. (1999). New Clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch Syndrome) proposed by the International Collaborative Group in ICG HNPCC. GASTROENTEROLOGY, 116(6): 1453-1456. DOI: 10.1016/S0016-5085(99)70510-X Times Cited: 957 (from Web of Science) Umar A; Boland CR; Terdiman JP; et al. (2004). Revised Bethesada Guidelines for nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 96(4): 261-268. DOI: 10.1093/jnci/djh034 Published: FEB 18 2004 Times Cited: 785 (from Web of Science) Aaltonen LA; Salovaara R; Kristo P; et al. (1998). Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. NEW ENGLAND JOURNAL OF MEDICINE, 338(21): 1481-1487. DOI: 10.1056/NEJM199805213382101 Published: MAY 21 1998 Times Cited: 614 (from Web of Science) Jarvinen HJ; Aarnio M; Mustonen H; et al. (2000). Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. GASTROENTEROLOGY, 118(5): 829-834. DOI: 10.1016/S0016-5085(00)70168-5 Times Cited: 543 (from Web of Science) Aarnio M; Sankila R; Pukkala E; et al. (1999). Cancer risk in mutation carriers of DNA-mismatchrepair genes. INTERNATIONAL JOURNAL OF CANCER, 81(2): 214-218. DOI: 10.1002/(SICI)10970215(19990412)81:2<214::AID-IJC8>3.0.CO;2-L Times Cited: 474 (from Web of Science) Thibodeau SN; French AJ; Cunningham JM; et al. (1998). Microsatellite instability in colorectal cancer: Different mutator phenotypes and the principal involvement of hMLH1, CANCER RESEARCH, 58(8): 1713-1718. Times Cited: 387 (from Web of Science) Hampel H; Frankel WL; Martin E; et al. (2005). Screening for the Lynch syndrome ( Hereditary

Colon Cancer Guide 30 nonpolyposis colorectal cancer).NEW ENGLAND JOURNAL OF MEDICINE, 352(18): 1851-1860. DOI: 10.1056/NEJMoa043146 Times Cited: 325 (from Web of Science) Weitz J; Koch M; Debus J; et al. (2005). Colorectal cancer. LANCET, 365(9454): 153-165 DOI: 10.1016/S0140-6736(05)17706-X Times Cited: 309 (from Web of Science) Sheehan KM; Sheahan K; O'Donoghue DP; et al. (1999). The relationship between cyclooxygenase-2 expression and colorectal cancer.JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 282(13): 1254-1257. DOI: 10.1001/jama.282.13.1254 Published: OCT 6 1999 Times Cited: 280 (from Web of Science) Salovaara R; Loukola A; Kristo P; et al. (2000). Population-based molecular detection of hereditary nonpolyposis colorectal cancer. JOURNAL OF CLINICAL ONCOLOGY, 18(11): 2193-2200 Times Cited: 275 (from Web of Science) Wijnen JT; Vasen HFA; Khan PM; et al. (1998). Clinical findings with implications for genetic testing in families with clustering of colorectal. NEW ENGLAND JOURNAL OF MEDICINE, 399(8):511-518 DOI: 10.1056/NEJM199808203390804 Times Cited: 249 (from Web of Science) Kolodner RD; Tytell JD; Schmeits JL; et al. (1999). Germ-line msh6 mutations in colorectal cancer families.CANCER RESEARCH, 59(20): 5068-5074 Times Cited: 220 (from Web of Science)

Interesting Newer Articles: Carlsson E. Ranki A. Sipila L. Karenko L. Abdel-Rahman WM; et. al. (2012). Potential role of a navigator gene NAV3 in colorectal cancer. British Journal of Cancer, 106(3):517-24. UI: 22173670 Corte Helene; Manceau Gilles; Blons Helene; et al. (2012). MicroRNA and colorectal cancer. DIGESTIVE AND LIVER DISEASE, 44(2): 195-200. DOI: 10.1016/j.dld.2011.10.010 Lubbe SJ. Di Bernardo MC. Broderick P. Chandler I. Houlston RS. (2012). Comprehensive evaluation of the impact of 14 genetic variants on colorectal cancer phenotype and risk. American Journal of Epidemiology. 175(1):1-10. UI: 22156018 Rahner Nils; Brockschmidt Felix F.; Steinke Verena; et al. (2012). Mutation and association analyses of the candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A in patients with unexplained MSH2deficient tumors. FAMILIAL CANCER, 11(1): 19-26 DOI: 10.1007/s10689-011-9489-z Ramsoekh D.; van Leerdam M.E.; Tops C.M.J.; Dooijes D.; Steyerberg E.W.; Kuipers E.J.; Wagner A. (2007). The use of genetic testing in hereditary colorectal cancer syndromes: Genetic testing in

Colon Cancer Guide 31 HNPCC, (A)FAP and MAP. Clinical Genetics(UK) , 72(6): 562-567. (DOI): 10.1111/j.13990004.2007.00912.x Slattery ML. Lundgreen A. Herrick JS; et. al. (2011). Variation in the CYP19A1 gene and risk of colon and rectal cancer. Cancer Causes & Control. 22(7):955-63, 2011 Jul. UI: 21479914 Tresallet Christophe; Brouquet Antoine; Julie Catherine; et al. (2012). Evaluation of predictive models in daily practice for the identification of patients with Lynch syndrome. INTERNATIONAL JOURNAL OF CANCER, 130(6): 1367-1377 DOI: 10.1002/ijc.26144 Walsh MD. Buchanan DD. Cummings MC. Pearson SA; et al. (2010). Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clinical Cancer Research, 16(7):2214-24, 2010 Apr 1. UI: 20215533 Additional Questions, Comments, or Concerns? Email me at kml254 at eden.rutgers.edu