Fruits, vegetables, and hMLH1 protein-deficient and -proficient colon cancer: The Netherlands cohort study.
BACKGROUND
Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.


METHODS
Associations between consumption of fruits and vegetables and hMLH1 protein-deficient and -proficient colon cancer were evaluated in the Netherlands Cohort Study on diet and cancer using a case-cohort approach. A self-administered food frequency questionnaire was completed, in 1986, by 120,852 individuals ages 55 to 69 years. Using immunohistochemistry, hMLH1 protein expression was assessed in colon cancer tissue obtained from 441 patients who were identified over 7.3 years of follow-up excluding the initial 2.3 years. Incidence rate ratios (RR) were estimated for hMLH1 protein-deficient and -proficient colon cancer.


RESULTS
hMLH1 protein expression was absent in 54 tumors (12.2%) and present in 387 tumors. Fruit consumption was associated with hMLH1 protein-deficient colon cancer [highest versus lowest tertile, RR, 0.46; 95% confidence interval (95% CI), 0.23-0.90; P(trend) = 0.029] but not with hMLH1 protein-proficient tumors (highest versus lowest tertile, RR, 1.03; 95% CI, 0.78-1.35; P(trend) = 0.81). Total consumption of vegetables was not associated with either type of tumor (hMLH1 protein deficient: RR, 0.86; 95% CI, 0.45-1.65; P(trend) = 0.67; hMLH1 protein proficient: RR, 0.94; 95% CI, 0.72-1.23; P(trend) = 0.72). No associations were observed for folate, fiber, antioxidants, or subgroups of vegetables.


CONCLUSIONS
These analyses indicate that an inverse association between consumption of fruits and colon cancer may be confined to the subgroup of tumors with a deficient mismatch repair system.
Wark
Petra A
PA
Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
Weijenberg
Matty P
MP
van 't Veer
Pieter
P
van Wijhe
Gerda
G
Lüchtenborg
Margreet
M
van Muijen
Goos N P
GN
de Goeij
Anton F P M
AF
Goldbohm
R Alexandra
RA
van den Brandt
Piet A
PA
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D002352:Carrier Proteins; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000209:etiology*; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D005638:Fruit; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000172:deficiency*; D009426:Netherlands / Q000453:epidemiology; D009687:Nuclear Proteins / Q000172:deficiency*; D014675:Vegetables
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004044:Dietary Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1