Involvement of genetic factors and lifestyle on the occurrence of colorectal and gastric cancer

Abstract

Gastrointestinal cancers are diseases due to genetic and environmental factors. In this present work we are interested in the influence of environmental factors on the occurrence of gastrointestinal cancers in Tunisian population. We found that the MTHFR C677T polymorphism was associated with colorectal cancer (P<0.04) but not with gastric cancer. In addition, we have shown that alcohol is associated with an increased risk of colorectal cancer, but the consumption of cheese is protective. Furthermore, we studied tymidylate synthase gene involved in folate metabolism. Indeed, we observed that the 5'UTR repeat polymorphism, is associated with risk of colorectal cancer, and the LL genotype (3R/3R) was significantly frequent in patients with colorectal cancer compared to controls (p=0.002; OR=2.7, 95% CI=1.4-5.2). While we found that SL genotype (2R/3R) was associated with risk of gastric cancer (p=0.015; OR=4.46, 95% CI=1.08-19-64). This polymorphism was also shown to be a predictor of response to chemotherapy based 5'-fluorouracil. However, we are interested in studying the GPX -1 gene involved in phase I metabolism of xenobiotics. We therefore evaluated the risk of TT genotype in GPX-1 C599T polymorphism with the onset of gastric cancer (P=0.0001; OR=5.41, 95% CI 1.98 to 15.58) and colorectal cancer (P=0.00008; OR=4.40, 95% CI 1.93 to 10.27). To clarify the possible relationship between environmental factors and the occurrence of the disease, we studied the additive effect of risk genotype and behavior in order to highlight the interaction of gene-environment factors.

Keywords: Colorectal cancer; Food; Gastric cancer; Interaction; Polymorphisms; Treatment.