Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas.
BACKGROUND
The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population.


METHODS
We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression.


RESULTS
A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious.


CONCLUSIONS
Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma.
Skjelbred
Camilla F
CF
Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, N-3710 Skien, Norway. camilla-furu.skjelbred@sthf.no
Saebø
Mona
M
Hjartåker
Anette
A
Grotmol
Tom
T
Hansteen
Inger-Lise
IL
Tveit
Kjell M
KM
Hoff
Geir
G
Kure
Elin H
EH
D000236:Adenoma / Q000209:etiology* / Q000235:genetics; D000368:Aged; D002277:Carcinoma / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D004435:Eating / Q000502:physiology*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology; D012307:Risk Factors; D014675:Vegetables
C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human