Colorectal adenomatous and hyperplastic polyps: Smoking and N-acetyltransferase 2 polymorphisms

Arylamine N-acetyltransferase 2 (NAT2) is involved in both the detoxificati on and bioactivation of carcinogenic arylamines and other mutagens, This en zyme is polymorphic, and the fast and slow phenotypes are thought to be ris k factors for colon and bladder cancer, respectively. Here, we report on a case-control study of adenomatous and hyperplastic polyps, with particular attention to tobacco smoking, a known risk factor for adenomas, and polymor phisms of NAT2, All participants underwent complete colonoscopy and were su bsequently divided into case and control groups on the basis of pathology. Cases were diagnosed with confirmed adenomas (n = 527) or hyperplastic poly ps (n = 200); controls (n = 633) had no history of colonic neoplasia and no polyps at colonoscopy, NAT2 genotype was determined using an oligonucleoti de ligation assay and fast, intermediate, or slow phenotype imputed. Multiv ariate-adjusted odds ratios (ORs) and 95% confidence intervals were compute d using logistic regression adjusting for age, sex, nonsteroidal antiinflam matory drug use, and hormone replacement therapy use. Smoking was associate d with an increased risk of adenomas [current versus never smoking OR = 2.0 (95% confidence interval, 1.4-2.9)] and hyperplastic polyps [current versu s never smoking OR = 4.1 (2.6-6.5)], NAT2 status among adenomatous polyp pa tients and hyperplastic polyp patients, respectively, showed ORs of 1.1 (0. 8-1.4) and 1.2 (0.8-1.6; intermediate versus slow) and 1.1 (0.6-1.9) and 0. 9 (0.4-1.9; fast versus slow). There were no differences in risk when adeno ma patients were stratified on multiplicity, size, or histopathological sub type of polyps. Never-smokers showed no variation in risk across acetylator status for either species of polyp, whereas current smokers showed ORs of 2.0 (1.2-3.2) and 2.3 (1.4-3.9) for adenomas and 3.9 (2.1-7.1) and 4.9 (2.6 -9.4) for hyperplastic polyps for slow and intermediate/fast NAT2, respecti vely, compared with slow-NAT2 never-smokers. Risks of both multiple [OR = 4 .3 (2.1-8.8)] and large [OR = 3.8 (1.9-75)] adenomas were somewhat elevated in current smokers with an intermediate/fast phenotype compared with smoke rs with a slow NAT2 phenotype, but the interaction was not statistically si gnificant. Risk of hyperplastic polyps and adenomatous polyps is strongly r elated to smoking. There is little suggestion of interaction between NAT2 s tatus and smoking and no relationship with NAT2 genotype alone.