N-acetyltransferase 2 (NAT2) genotype and colorectal carcinoma: Risk variability according to tumour site?

Background: Dietary heterocyclic aromatic amines (HAAs) are members of a fa mily of chemicals that comprise highly mutagenic compounds related to colon cancer. The polymorphic N-acetyltransferase 2 enzyme (NAT2, E.C. 2.3.1.5) plays a key role in the transformation of HAAs to ultimate carcinogens. NAT 2 enzyme activity is expressed in a genotype-dependent manner in colon epit helium. Therefore local activation of HAAs in colon, and hence increased ri sk to develop colon cancer, is likely to be related to high NAT2 enzyme act ivity. This study is aimed at analysing the association between genotypes l eading to high NAT2 activity and colorectal cancer risk. Methods: Genomic D NA from 120 colorectal cancer patients and 258 healthy individuals were ana lysed for enzyme-inactivating mutations at the coding region of the NAR gen e by means of a mutation-specific polymerase chain reaction. Results: Among patients with sigmoid colon cancer, a significant excess of individuals wi th genotypes leading to high NAT2 activity was observed as compared both to controls and to the rest of patients with colorectal cancer (P < 0.05). Co nclusions: Our findings, which require independent confirmation, suggest th at the NAT2 genotype constitutes a secondary risk factor to develop sigmoid colon cancer.