Consumption of fruits and vegetables, and expression of the mismatch repair gene hMLH1 in human colorectal cancer: a prospective study

Introduction: Striking clinical and pathological differences exist between colorectal carcinomas with and without defects in the mismatch repair system. Such defects are mainly due to loss of expression of the hMLH1 gene. Animal and in vitro studies suggest that fruits, vegetables and folate are associated with expression of mismatch repair genes in the colon and rectum. Methods: Associations between consumption of fruits and vegetables and expression of the hMLH1 mismatch repair gene were evaluated in The Netherlands Cohort Study using a case cohort approach. In 1986, 120 852 men and women aged 55–69 years completed a questionnaire on dietary and other postulated risk factors for cancer. After 7.3 years of follow up and with exclusion of the first 2.3 years, hMLH1 protein expression was assessed in colorectal cancer tissue obtained from 725 incident colorectal cancer patients using immunohistochemistry. hMLH1 protein expression was absent in 61 cases (8.4%). Risk ratios (RR) were computed to compare cases with and without hMLH1 expression to the sub cohort. In this abstract, preliminary results based on 38 cases without and 432 with expression of hMLH1 are reported. During the conference, results based on the entire study population will be presented. Results: Consumption of fruits was associated with hMLH1 deficient colorectal carcinomas (RRhighest v lowest tertile 0.28; 95% CI 0.12 to 0.66), but not with carcinomas expressing hMLH1 (RRhighest v lowest tertile 0.96; 95% CI 0.74 to 1.24). Total consumption of vegetables was not associated with both types of tumours (without hMLH1 expression: RR 0.78; 95% CI 0.38 to 1.16; with hMLH1 expression: RR 0.91; 95% CI 0.71 to 1.16). Brassica vegetables, folate, and vitamin C tended to be inversely associated with hMLH1 deficient carcinomas, but not with carcinomas expressing hMLH1. Conclusions: These analyses suggest that inverse associations between consumption of fruits, brassica vegetables, folate, and vitamin C might be confined to the subgroup of hMLH1 deficient colorectal carcinomas.