Original article
Environmental Factors and Colorectal Tumor Risk in Individuals With Hereditary Nonpolyposis Colorectal Cancer

https://doi.org/10.1016/j.cgh.2007.02.019Get rights and content

Background & Aims: Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) are at increased risk for colorectal cancer. Environmental factors might play a role in HNPCC-associated carcinogenesis. The aim of this study was to gain insight into the effects of environmental factors on colorectal tumor risk in individuals with HNPCC. Methods: We examined associations between dietary factors, cigarette smoking, and HNPCC-associated colorectal tumors in a Dutch case-control study (145 cases, 103 tumor-free controls; all study participants were known or suspected carriers of a germline mutation in one of the DNA mismatch repair genes). We also assessed associations between the various environmental factors and occurrence of adenomatous polyposis coli (APC) mutations in HNPCC-associated polyps in a subset of the study population. Results: Fruit consumption was inversely associated with ever developing HNPCC-associated colorectal tumors (odds ratio [95% confidence interval] for highest vs lowest tertile, 0.4 [0.2–0.9]; Ptrend = .03); a borderline significant inverse association was observed for dietary fiber intake (0.5 [0.2–1.0]; Ptrend = .06). Cigarette smoking seemed to increase the risk of HNPCC-associated colorectal tumors. Truncating APC mutations were detected in 30 (37.5%) of the 80 available HNPCC-associated polyps; frameshift mutations were most common (73.3%). None of the evaluated environmental factors was distinctively associated with a specific APC status of the polyps. Conclusions: Our data suggest that fruit consumption and dietary fiber intake might decrease the risk of colorectal tumors in individuals with HNPCC, whereas cigarette smoking might increase the risk of HNPCC-associated colorectal tumors. The observed associations support the hypothesis that HNPCC-associated outcomes might be modified by environmental factors.

Section snippets

Study Population

Participants for this case-control study on environmental factors and HNPCC-associated colorectal tumors were recruited in the Netherlands between April 1999–April 2002. All participants belonged to a family fulfilling the Amsterdam criteria for HNPCC20, 21 and were known or suspected carriers of a germline mutation in one of the MMR genes. (Amsterdam criteria: at least 3 relatives with colorectal cancer [Amsterdam criteria I] or another HNPCC-associated cancer [ie, endometrial, stomach, ovary,

Results

Characteristics of the study population are presented in Table 1. In total, the study population consisted of 73 known carriers (hMLH1, 49 [67%]; hMSH2, 22 [30%]; gene not disclosed to us, 2 [3%]). The frequency of known carriers did not differ significantly between cases and controls. Of the cases with unknown carrier status (n = 100), 26 (26%) had been diagnosed with at least one adenomatous polyp before 40 years of age, and 14 (14%) had been diagnosed with colorectal cancer before 50 years

Discussion

In this study, we evaluated associations between various environmental factors reported previously to be associated with sporadic colorectal cancer risk and the occurrence of colorectal tumors in known or suspected carriers of a germline mutation in one of the MMR genes. As anticipated, age at last colonoscopy was strongly, positively associated with ever been diagnosed with colorectal tumors in our study population. Fruit consumption lowered the risk of ever developing HNPCC-associated

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  • Cited by (0)

    Supported by the Dutch Cancer Society (grant LUW 98-1687).

    1

    Dr Diergaarde is currently affiliated with the Fred Hutchinson Cancer Research Center, Seattle, Washington.

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