COLON CANCER

EVIDENCE BASED NURSING

Submitted by: Evardone, Inah D. Garcia, Clara Maey S. Go, Frank Martin A. Guernaldo, Geneva G. Hubilla, Joly M. Javier, Kathrine L. BSN203

I. Clinical Question:
Are men more likely to be at risk than women to have colon cancer?

II. Citation:
Sex-Specific Differences in Colon Cancer Associated With p53 Mutations

REFERENCE: http://web.ebscohost.com/ehost/pdfviewer/ pdfviewer?sid=da9f6c12-2e0b-4267-a51a 9834cbbd5e42%40sessionmgr112&vid=1&hi d=112

III. Study Characteristics

a. Patient included Study participants were African American, white, or Hispanic and were from the Kaiser Permanente Medical Care Program (KPMCP) of northern California, an eight county area in Utah (Davis, Salt Lake, Utah, Weber, Wasatch, Tooele, Morgan, and Summit counties), or the Twin Cities metropolitan area in Minnesota. The study population was approximately 90% non-Hispanic white, 5% African American, and 5% Hispanic.

 Subject Selection Inclusion Criteria Eligibility criteria for cases included diagnosis with first-primary incident colon cancer (ICD-O, 2nd ed., codes 18.0 and 18.218.9) between October 1, 1991, and September 30, 1994; between 30 and 79 yr of age at time of diagnosis; and mentally competent to complete the interview. Exclusion Criteria Cases with adenocarcinoma or carcinoma of the rectosigmoid junction or rectum (defined as the first 15 cm from the anal opening) with known familial adenomatous polyposis, ulcerative colitis, or Crohns disease were not eligible.

 b. Interventions compared The study doesnt show any intervention to be compared. However in this study, the researchers evaluate sex-specific associations with acquired p53 mutations in colon tumors by examining both estrogen- and insulin-related variables.

 c. Outcome monitored Sex-specific differences in observed incidence rates, tumor subsite, and diet and lifestyle associations with colon cancer have been observed. The study evaluates sex-specific associations with p53 mutations in colon cancer to add to understanding of these differences.

 d. Does the study focus in significant problem in clinical practice? Yes, the study focuses on a significant problem in clinical practice because cancer is known as one of the major cause of death in the world

IV. Methodology/Design
Data were collected by trained and certified interviewers using laptop computers. The referent period for the study was the calendar year, approximately 2 year prior to date of diagnosis or date of interview for controls. Using this referent period, information was collected on dietary intake using a detailed diet history questionnaire. Methods for obtaining tumor tissue have been described. Colon cancer tissue was micro dissected and DNA was extracted from formalin-fixed paraffin-embedded tissue blocks as described. Exons58 of 53 and relevant intron/exon boundaries were polymerase chain reaction (PCR) amplified with the primers.

All tumor samples corresponding to any abnormally migrating SSCP bands were reamplified with the respective primers tailed with UP and RP (and without dye labeling) for sequencing. PCR products were sequenced using prism Big Dye terminators and cycle sequencing with Taq FS DNA polymerase. DNA sequence was collected and analyzed on an ABI prism 377 automated DNA sequencer. Any alterations were verified by sequencing in both directions. SSCP was also performed on the respective germ line DNA sample of any tumor with a nonhot-spot missense mutation, insertion or deletion mutations that consisted of multiples of three bases, and splice-site mutations to verify that it was an acquired rather than inherited mutation. Sex-specific associations with acquired p53 mutations were evaluated by examining age, tumor site, and estrogen- related factors.

 Design Data from a large population-based incident case-control study of colon cancer were used to evaluate age and gender associations with p53 mutations. To obtain a better understanding of gender- specific associations, we evaluated the role of estrogen as a mediator of risk. For these analyses, women were classified as estrogen positive or negative, based on menopausal status and use of hormone replacement therapy (HRT). Setting Northern California

Has the original study been replicated?

No, the study is original and has not been replicated.

What were the risks and benefits of the nursing action/intervention tested in the study?
Observations that hormone replacement therapy (HRT) reduces risk of colorectal cancer provide a biological basis for some of the observed sex-specific differences in colorectal cancer reported . Sex-specific associations have been attributed to many factors, including the effect of estrogen on tumor development and differences in gut metabolism observed for men and women. Benefit from the study is the ability to examine tumors that unravel our understanding of colon cancer by allowing us to observe unique diet and lifestyle associations with specific tumor characteristics

RESULT of STUDY
There was a significant interaction between age and sex and risk of an acquired p53 mutation compared with p53 Wt. Among men, there was an increase in p53 mutations with age, whereas among women the opposite was observed. Associations with parity, oral contraceptive use, and total ovulatory months were not associated with p53 mutations. However, recent use of HRT reduced risk of all tumors, as did being estrogen positive. Women who were estrogen positive (either premenopausal or recent users of HRT) were at a significantly increased risk of an acquired p53 mutation if they consumed a diet with a high sugar index (odds ratio = 2.94; 95% confidence interval = 1.47 5.89); similar increases in risk of p53 mutations were not observed for men or women who were estrogen negative.

Authors Contributions/ Recommendations

Although sex-specific associations were detected for acquired p53 mutations, they do not indicate a unique role of estrogens in the mutation of p53. These data are consistent with a role for estrogen in altering susceptibility to diet and lifestyle factors possibly via an insulin-related mechanism. Sexspecific associations with colon cancer have been repeatedly observed. Men have higher incidence rates of colon cancer; women have more proximal tumors than men; and women have an increased risk of polyp recurrence on a high-carbohydrate diet, whereas men do not.

Observations that hormone replacement therapy (HRT) reduces risk of colorectal cancer provide a biological basis for some of the observed sexspecific differences in colorectal cancer reported . Sex-specific associations have been attributed to many factors, including the effect of estrogen on tumor development and differences in gut metabolism observed for men and women. Ability to examine tumors is helping to unravel our understanding of colon cancer by allowing us to observe unique diet and lifestyle associations with specific tumor characteristics. Our recent work and that by others suggest that estrogens may protect against tumors with microsatellite instability (MSI).

This observation helps to explain both patterns of MSI in tumors and possibly tumor subsite differences between men and women .Associations between p53 immunohistochemistry-positive tumors and oral contraceptive use also have been reported (12). Dietary glycemic index (GI) has been reported as being more strongly associated with p53 mutations in women than in men (13). Taken together, this may suggest that estrogen-related factors are associated with acquired p53 mutations. Explanations that account for both steroid (that is, estrogen) and growth hormones (that is, insulin) may better integrate the role of established risk factors. Body size is related to a variety of metabolic phenomena that may influence cellular proliferation.

A large body mass index (BMI) is associated with both insulin resistance and alterations in estrogen metabolism and function (14,15). Likewise, physical activity appears to play an important role in the regulation of both estrogen and insulin (16,17). In this article, we evaluate sex-specific associations with acquired p53 mutations in colon tumors by examining both estrogen-and insulin-related variables. We hypothesize that estrogen is associated with p53 mutations that may involve regulation of insulin-related mechanisms. Physical activity, BMI, and dietary sugar may be further modified by estrogen as they relate to p53 tumor mutations.

V. Applicability
a.) Does the study provide a direct enough answer to your clinical question in terms of type of patients, intervention and outcome?
The study had and answered the clinical question adequately. With regards to the patients, Acquired p53 mutations were detected in 48.4% of colon tumors in men and in 45.4% of colon tumors in women .A significant difference in age was observed for men and women when comparing those with a p53 mutation with those whose tumor did not have a p53 mutation therefore answering the question that Sexes specifically differs in colon cancer associated with p53 mutations.

b.) Is it feasible to carry out the nursing action in the world? Yes, with the understanding of the difference of occurrence of colon cancer with p53 mutations between sexes it can really help us nurses to be knowledgeable about patients who are most prone of having colon cancer when it comes to specific sexes.

Reviewers Conclusion/ Commentary

The study shows that men are more likely to have colon cancer than women. As a conclusion, we can say that this study does not only give us the idea about cancer but it also gives us the idea on how we can prevent it from occurring to our life. This study can also set as an eye-opener to everyone about the different causes of cancer. However, even though the study shows that men more likely to have colon cancer women should not be too confident because the percentage difference between the two genders are not large meaning women are still at risk if they are not going to take good care of their body.

Evaluating Nursing Care Process

Safety
All patients chosen in the study are mentally competent to finish the interview. Researchers found out that old men are more at risk in colon cancer than old women. In addition, they hypothesized that longer exposure to estrogen and high sugar diet could lead to colon cancer among women. Use of Hormone Replacement Therapy decreases risk to colon cancer among women.

 The study used a test that determines the etiology of the cancer of the patient. It helps the patient to watch what diet or lifestyle is appropriate associated to their cancer.

Competence of the Health care provider

Data were collected by trained and certified interviewers; and are technologically proficient. Specialized surgeons take the tumor tissues for biopsy, and medical technologists interpret the results.

Acceptability
The study evaluates sex-specific associations with mutations in colon cancer to add to understanding of the differences. Data from a large population-based incident case-control study of colon cancer were used to evaluate age and gender associations with mutations. To obtain a better understanding of gender-specific associations, we evaluated the role of estrogen as a mediator of risk. Acquired mutations were detected in 48.4% of colon tumors in men and in 45.4% of colon tumors in women. Intervention used is suitable to the patients situation and acceptable to use to provide therapeutic effect on patients.

Appropriateness
Interventions used, time and setting are appropriate to the patients. Study participants were African American, white, or Hispanic and were from the Kaiser Permanente Medical Care Program (KPMCP) of northern California. Knowledge on the proper treatment is necessary in order to provide care that is acceptable and appropriate for both the nursing actions and client

 The study was safe and convenient for the patients. And it is helpful based from the fact that they got the knowledge to avoid what cause their cancer.