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 NAT25C-T341C, NAT26B-G590A, NAT27B-G857A, NAT218-A845C, and NAT25A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT25C-T341C, NAT27B-G857A, and NAT25A-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.