N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer

Objectives: The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes.

Methods: Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis.

Results: The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A, and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (P<.001), 7.7 (P<.001), 7.83 (P<.001), 7.51 (P<.001), and 8.62 (P<.001), respectively. Alcohol consumption associated with the NAT2 -T341C, G590A, G857A, A845C, and C481T rapid acetylator allele induces a risk of 10.63 (P<.001), 12.04 (P<.001), 9.76 (P<.001), 10.25 (P<.001), and 9.54 (P<.001), respectively, for colon cancer, whereas the risk for rectal cancer is 9.72 (P<.001), 11.24 (P<.001), 13.07 (P<.001), 10.04 (P<.001), and 9.43 (P<.001), respectively. Smokers with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele have a risk of 4.87, 4.25, 4.18, 3.81, and 3.82, respectively, to develop colon cancer.

Conclusions: Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants.