NAT2 Gene Polymorphism and Sporadic Colorectal Cancer. Prevalence, Tumor Stage and Prognosis. A Preliminary Study in 70 Patients

Abstract

Aim. Theoretically, individuals with a NAT2 rapid acetylator genotype are exposed to a higher risk of developing colorectal cancer. We attempted to study this relationship.

Material and methods. We evaluated a group of 70 patients with sporadic colorectal cancer and 40 controls. We calculated the relative risk for patients homozygous for the normal allele NAT2*5C, NAT2*5A, NAT2*6B, NAT2*7B, for heterozygous patients and for patients homozygous for the mutant allele.

Results. We found an increased risk for patients with a rapid acetylator genotype to develop colorectal cancer. Rapid acetylators, homozygous negative or heterozygous for the NAT2*5C, NAT2*5A and NAT2*6B mutations have an increased risk of colorectal cancer compared to homozygous positive patients.The analysis of the NAT2*5C genotype shows that the majority of the cases are at stage pT3 for rapid acetylators, 41 cases (74.54%), compared to slow acetylators, where the majority of cases are at stage pT4, 10 cases (66.66%) (p<0.05). The genotype with a rapid acetylator phenotype of the NAT2*5C, NAT2*5A and NAT2*7B variants was most frequently associated with Dukes stage B. The NAT2*5C, NAT2*5A and NAT2*7B gene variants with a slow acetylator pheno-type were most frequently associated with Dukes stage C.

Conclusions. Rapid acetylators, homozygous negative or heterozygous for the NAT2*5C, NAT2*5A and NAT2*6B mutations have a higher risk of colorectal cancer compared to positive homozygotes. Rapid acetylators have earlier stages of colorectal cancer and a better prognosis than slow acetylators, who are diagnosed in more advanced stages.