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ORIGINAL ARTICLE
Year : 2010  |  Volume : 47  |  Issue : 1  |  Page : 27-30
 

Risk of colorectal cancer in relatives: A case control study


Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University (M.C), Tehran, Iran

Date of Web Publication12-Jan-2010

Correspondence Address:
B Moghimi-Dehkordi
Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University (M.C), Tehran
Iran
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Source of Support: Research Center of Gastroenterology and Liver Diseases and its staff, Conflict of Interest: None


DOI: 10.4103/0019-509X.58855

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 » Abstract 

Background: In around 10 to 15% of all colorectal cancer (CRC) cases, a positive family history of colorectal cancer is observed . Although increased risk of colorectal cancer in individuals with a family history of the disease has been observed consistently in the past studies, limited information is available on colorectal cancer associated with family history in Iran. Aims : The purpose of this study is to define the risk of colorectal cancer associated with a family history of cancer. Setting and Design: The present study was designed as an unmatched case control study. The cases were 393 patients with histologically confirmed colorectal carcinomas and there were 393 controls, randomly selected from among the healthy participants in a health survey. Methods : The family history was extracted from a standard history form completed by the patient or from the record created by a health care provider. Statistical Analysis: Mantel-Heanszel Odds Ratio was computed for removing the confounding effect of age and sex. Results : A positive family history of cancer was reported by 36.4 and 24.4% among the cases and controls, respectively. Colorectal cancer risk increased two-fold in subjects who reported having first degree relatives with cancer. The adjusted odds ratio was 4.76, indicating that having a positive family history of colorectal cancer among relatives increased one's risk of colorectal cancer about 4.5-fold. Conclusion: According to our findings, a family history of cancer increased the risk of CRC. Due to this fact that there is no current colorectal cancer screening program in Iran, it is recommended that first degree relatives of patients with colorectal cancer should be considered as a priority group for screening programs.


Keywords: Colorectal cancer, family history of cancer, relatives


How to cite this article:
Safaee A, Moghimi-Dehkordi B, Pourhoseingholi M A, Vahedi M, Maserat E, Ghiasi S, Fatemi S R, Zali M R. Risk of colorectal cancer in relatives: A case control study. Indian J Cancer 2010;47:27-30

How to cite this URL:
Safaee A, Moghimi-Dehkordi B, Pourhoseingholi M A, Vahedi M, Maserat E, Ghiasi S, Fatemi S R, Zali M R. Risk of colorectal cancer in relatives: A case control study. Indian J Cancer [serial online] 2010 [cited 2019 Apr 23];47:27-30. Available from: http://www.indianjcancer.com/text.asp?2010/47/1/27/58855



 » Introduction Top


Colorectal cancer (CRC) is the fourth most common form of cancer occurring worldwide. [1] According to the Iranian Annual National Cancer Registration Report, CRC is the third common cancer in women and fifth in Iranian men and the incidence of colorectal cancer has increased during the last 25 years. [2]

Most cases of CRC (around 80%) are probably caused by environmental factors. In up to 5% of all colorectal cancers, genetic factors play a dominant role. [3],[4] The most common hereditary syndromes are Lynch syndrome (hereditary nonpolyposis colorectal cancer), familial adenomatous polyposis (FAP), and MUTYH-associated polyposis (MAP). [5]

In around 10 to 15% of all CRC cases, a positive family history of colorectal cancer is observed. [6] It is probable that dietary and other environmental risk factors, acting solely or in concert with genetic factors, influence the aggregation of the disease. [7]

The risk associated with a family history of CRC depends on the number of affected relatives and the age at diagnosis. [8] Subjects with one first-degree relative (FDR) with CRC diagnosed at age > 50 years, have a relative risk (RR) of 2 to 3.15 for developing CRC. Subjects with two (or more) FDRs, with CRC diagnosed at any age, or with one FDR with CRC diagnosed before the age of 50 years, have a relative risk of 4 to 6 for developing CRC. [7]

Although increased risk of colorectal cancer in individuals with a family history of the disease has been observed consistently in past studies, limited information is available on colorectal cancer associated with family history in Iran. The purpose of this study is to define the colorectal cancer risk associated with a family history of cancer.


 » Materials and Methods Top


The present study was designed as an unmatched case control study, to assess the impact of a family history (FH) of first and second degree relatives with cancer on patients with CRC.

The cases were 393 patients (231 males and 162 females), not above the age of 89 years (median age 53.5 ± 14.15 years), who had been histologically confirmed as having colorectal carcinomas, with no previous diagnosis of any cancer, and had registered in one cancer registry center in Tehran, Iran. This center is a referral center for GI cancer, and patients referred to this cancer registry from both public and private hospitals. A total of 393 controls were randomly selected from among the healthy participants in a health survey conducted by the Department of Health System Research of the Research Center for Gastroenterology and Liver Diseases (RCGLD), in which a total of 5500 subjects, of age ≥ 15 years, were invited to participate in an interview regarding the occurrence of colorectal cancer in their first- or second-degree relatives.

The cases were asked whether family member(s) had been diagnosed with colorectal cancer or any other cancer. Positive family history was defined when the case had at least one first- (mother, father, children, or sibling) or second- (grandfather or mother, aunt or uncle) degree relative diagnosed with any malignancy. The FH was extracted from a standard history form completed by the patient or from the record created by a health care provider. In all cases where a possible indication of colorectal malignancy among relatives was given, further information on the identity of the diseased relative was gathered. The ethical committee at Shahid Beheshti University approved the study.

Because the patients were slightly older than the controls, the Odds Ratio (OR), together with their 95% confidence interval, for colorectal cancer, according to the histories of selected malignant neoplasm in first- and second-degree relatives were computed from data stratified for age group and sex, with the Mantel-Haenszel procedure. All tests were two sided, with statistical significance attributes to p < 0.05. Statistical analysis was performed with SPSS software (version 13.0).


 » Results Top


58.8% of cases and 49.6% of controls were male. The mean age of the cases and controls was 53.5 and 44.2 years, respectively. A positive family history of cancer was reported by 36.4% of the cases and 24.4% of the controls.

[Table 1] shows the distribution of cases and controls according to the FH of cancer and the number of affected relatives. Colorectal cancer risk increased two-fold for subjects reporting any first-degree relative with cancer. Having two or more affected first-degree relatives was associated with a further elevation in colorectal cancer risk (OR 2.38, 95% confidence interval: 1.13 - 6.02). The risk of colorectal cancer was slightly increased for subjects with a positive history of cancer in second-degree relatives.

[Table 2] shows the number of cases and controls with history of colorectal and other site cancers in first- and second-degree relatives, and the corresponding ORs. Overall, 15.5% of the cases versus 2.3% of the controls reported a family history of colorectal cancer. The adjusted odds ratio quantifying the overall familial aggregation was 4.76 (95% CI 2.79-8.13), indicating that having a positive family history of colorectal cancer among relatives increases one's risk of colorectal cancer 4.5-fold.

The OR was 3.22 in subjects reporting a first-degree relative with colorectal cancer, compared to subjects with no family history of cancer. The risk of colorectal cancer was slightly elevated for subjects reporting any first-degree relative with cancer in other sites. None of the other cancer sites in second-degree relatives showed a significant association with risk of colorectal cancer. There was no significant association between the family history of cancer and the site of the tumor (p > 0.05).


 » Discussion Top


This case control study revealed an increased colorectal cancer risk associated with family history of colorectal cancer. Colorectal cancer risk was especially high when first-degree relatives were affected. A number of prospective and retrospective studies had been performed previously to delineate the increased risk for families, but this study is the first Iranian report. The present study confirmed previous reports that patients with a family history of colorectal cancer have an increased risk of developing malignant lesions in the large bowel. [4],[9],[10]

We demonstrated a significant positive correlation between the number of affected relatives per family and the risk, which increased nearly threefold if more than one relative was affected. These estimates are in general agreement with those reported in the previous studies. [11],[12]

Increasing CRC risk among those with a first-degree relative with cancer may be explained by a recessive gene and / or shared environment during a specific time period. Some observational studies show joint effects between a family history in a first-degree relative and environmental factors in CRC risk. [6],[13],[14] However, with this study design, it is not clearly possible to distinguish between a genetic and an environmental component of an observed familial predisposition.

Identification of a family history of cancer - especially a family history of colorectal cancer - is important for the management and prevention of colorectal cancer, and selective screening may be based on information obtained from a detailed family history of first- and second-degree relatives of cancer patients. On the other hand, assessing a first-degree relative with CRC in the general population may identify a greater number of persons who are at risk of colorectal cancer. As diagnoses of relatives reported by patients are useful in assessing risks, [15] we suggest a paramedical staff be trained for this purpose.

Due to the fact that there is no current colorectal cancer screening program in Iran, it is recommended that first-degree relatives of patients with colorectal CRC be considered as a priority group for screening programs.

There were limitations to the study. First, a family history of cancer was assessed using self-report questionnaires; however, the accuracy of self-reported data may not be optimal. We did not validate the patients' reports of family history against external sources, such as medical records. Second, we did not access the age at diagnosis of cancer in the relatives. On the other hand, we did not access the environmental factors to observe their impact on cancer. The exact age at cancer diagnosis for first-degree relatives was not available and this was another limitation of our study.

In conclusion, according to our findings, a family history of cancer increases the risk of CRC. Therefore, appropriate screening strategies especially genetic screening in first-degree relatives of young patients (younger than 50 years) should be considered, to prevent and control colorectal cancer, in Iran.


 » Acknowledgments Top


We would like to thank the Research Center of Gastroenterology and Liver Diseases and its staff for their valuable collaboration and financial support for this study.

 
 » References Top

1.Moghimi-Dehkordi B, Safaee A, Zali MR. Prognostic factors in 1,138 Iranian colorectal cancer patients. Int J Colorectal Dis 2008;23:683-8.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Azadeh S, Moghimi-Dehkordi B, Fatem SI, Pourhoseingholi M, Ghiasi S, Zali M. Colorectal cancer in iran: An epidemiological study. Asian Pac J Cancer Prev 2008;9:123-6.  Back to cited text no. 2      
3.Slattery ML, Levin TR, Ma K, Goldgar D, Holubkov R, Edwards S. Family history and colorectal cancer: predictors of risk. Cancer Causes Control 2003;14:879-87.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Samowitz WS, Curtin K, Lin HH, Robertson MA, Schaffer D, Nichols M, et al. The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer. Gastroenterology 2001;121:830-8.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Jass JR. Familial colorectal cancer: pathology and molecular characteristics. Lancet Oncol 2000;1:220-6.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Fernandez E, La Vecchia C, Talamini R, Negri E. Joint effects of family history and adult life dietary risk factors on colorectal cancer risk. Epidemiology 2002;13:360-3.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.de Jong AE, Vasen HF. The frequency of a positive family history for colorectal cancer: a population-based study in the Netherlands. Neth J Med 2006;64:367-70.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Kerber RA, Slattery ML, Potter JD, Caan BJ, Edwards SL. Risk of colon cancer associated with a family history of cancer or colorectal polyps: the diet, activity, and reproduction in colon cancer study. Int J Cancer 1998;78:157-60.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 2001;96:2992-3003.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Lynch KL, Ahnen DJ, Byers T, Weiss DG, Lieberman DA. First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer. Clin Gastroenterol Hepatol 2003;1:96-102.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Ling BS, Moskowitz MA, Wachs D, Pearson B, Schroy PC. Attitudes toward colorectal cancer screening tests. J Gen Intern Med 2001;16:822-30.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Acheson LS, Wiesner GL, Zyzanski SJ, Goodwin MA, Stange KC. Family history-taking in community family practice: implications for genetic screening. Genet Med 2000;2:180-5.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Fuchs CS, Willett WC, Colditz GA, Hunter DJ, Stampfer MJ, Speizer FE, et al. The influence of folate and multivitamin use on the familial risk of colon cancer in women. Cancer Epidemiol Biomarkers Prev 2002;11:227-34.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.La Vecchia C, Gallus S, Talamini R, Decarli A, Negri E, Franceschi S. Interaction between selected environmental factors and familial propensity for colon cancer. Eur J Cancer Prev 1999;8:147-50.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  
15.Katballe N, Juul S, Christensen M, Orntoft TF, Wikman FP, Laurberg S. Patient accuracy of reporting on hereditary non-polyposis colorectal cancer-related malignancy in family members. Br J Surg 2001;88:1228-33.  Back to cited text no. 15      



 
 
    Tables

  [Table 1], [Table 2]

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