Environmental factors and colorectal tumor risk in individuals with hereditary nonpolyposis colorectal cancer.
OBJECTIVE
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]; P(trend) = .03); a borderline significant inverse association was observed for dietary fiber intake (0.5 [0.2-1.0]; P(trend) = .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.
Diergaarde
Brenda
B
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
Braam
Hanneke
H
Vasen
Hans F
HF
Nagengast
Fokko M
FM
van Muijen
Goos N P
GN
Kok
Frans J
FJ
Kampman
Ellen
E
D011125:Adenomatous Polyposis Coli / Q000453:epidemiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018389:Codon, Nonsense; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics; D015897:Comorbidity; D004032:Diet; D004043:Dietary Fiber / Q000008:administration & dosage; D005260:Female; D016368:Frameshift Mutation; D017491:Genes, APC / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D018570:Risk Assessment; D012907:Smoking / Q000453:epidemiology
D018389:Codon, Nonsense; D004043:Dietary Fiber