Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

Abstract

BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionAlthough, 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.

GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group

“…The overall genotype distribution is not different from data on Caucasians with colorectal carcinoma (Ile/Ile 47, Ile/Val 46 and Val/Val 6%) (Skjelbred et al, 2007). A similar distribution is also found in CAPIRI patients, but not in those receiving CAP.…”

System review and metaanalysis of the relationships between five metabolic gene polymorphisms and colorectal adenoma risk

“…Previous epidemiological studies have indicated that red meat consumption and smoking were associated with increased CRA risk; in contrast, fruit and vegetable intake were associated with decreased CRA risk [6,7], but the results were inconsistent from country to country [6], which indicated that polymorphisms in genes encoding the enzymes involved in the metabolism of dietary chemicals may be responsible for the differences [4,8]. Phase I metabolic enzymes including cytochrome P450 1A1 (CYP1A1), CYP1A2 and microsomal epoxidehydrolase 1 (EPHX1) can catalyze the hydrolysis of arene, alkene and aliphatic epoxides to less reactive and more watersoluble dihydrodiols but catalyze the polycyclic aromatic hydrocarbons, which are mainly from cooked meat or cigarette to a more carcinogenic form [9,10].…”

Polymorphisms of biotransforming enzymes (GSTs) and their association with colorectal cancer in the Slovak population

“…In contrast, a significant association of GSTM1 null genotype carriers and an increased CRC risk was described in a recent study. Some case-control studies provide evidence that the presence of GSTM1 in conjuction with low intake of cruciferous vegetables is an important risk factor for CRC or pre-cancerous lesions [18,19].…”