Association of NAT2 Gene Polymorphisms with Susceptibility to Esophageal and Gastric Cancers in the Kashmir Valley

Abstract

Background and Aims: The high incidence of gastrointestinal cancers in the Kashmir Valley has been attributed to the presence of many chemical carcinogens such as nitrosamines and heterocyclic amines in tobacco and salted tea. Due to functional polymorphisms of the N-acetyltransferase 2 (NAT2) gene, there may be interindividual differences in the metabolism of heterocyclic amines. We undertook this study to determine the influence of NAT2 gene polymorphisms (rs1799929, rs1799930, rs1799931) as well as their interactions with environmental carcinogens on the modulation of risk of esophageal and gastric cancers (EC and GC) in the Kashmir Valley. Methods: A case/control study was performed involving 398 study subjects (182 controls, 123 EC and 93 GC). DNA samples were genotyped by PCR-RFLP method. Results: None of the three NAT2 polymorphic alleles was found to be independently associated with risk of EC/GC but haplotypes C481A590G857 and T481A590G857 significantly modulated the risk of EC and GC, respectively (OR = 0.56; 95% CI = 0.34-0.91; p = 0.018 and OR = 4.61; 95% CI = 1.90-11.17; p = 0.001). NAT2 slow acetylator genotypes (NAT2*5, NAT2*6, NAT2*7) significantly increased the risk of esophageal squamous cell carcinoma (ESCC, OR = 1.73; 95% CI = 1.01-2.97; p = 0.047). Smoking and salted tea consumption were independent risk factors, but they did not show any interaction with NAT2 slow acetylator genotypes. Conclusions: NAT2 slow acetylator genotype may increase susceptibility to ESCC, and NAT2 haplotypes (C481A590G857 and T481A590G857) may predict susceptibility to EC and GC in the Kashmir Valley. © 2009 IMSS.