Association of genetic polymorphisms of N-acetyltransferase 2 and susceptibility to esophageal cancer in north Indian population.
Esophageal cancer is multifactorial disease involving environmental and genetic risk factors. Tobacco smoke and alcohol are strong environmental risk factors. N-acetyltransferase 2 (NAT2) is known to metabolize heterocyclic amine carcinogens in tobacco smoke. The purpose of this study was to determine whether genetic polymorphism in the NAT2 and their interaction with environmental factors influence the susceptibility for esophageal cancer. For our study, 126 patients and 164 controls were genotyped for NAT2 2 * 5, 2 * 6 and 2 * 7 polymorphisms using PCR-RFLP method. In a case-control study, NAT2 slow acetylator genotype was not significantly associated with risk of esophageal cancer (OR 1.3, 95%CI = 0.78-2.2, P = 0.28). There was significant linkage disequilibrium between 2 * 5-2 * 6 and 2 * 5-2*7 (P < 0.05). Using expectation maximization algorithm, 6 haplotypes were obtained but none of them revealed any significant contribution to disease susceptibility. In case only analysis, the smokers with rapid acetylator were at slightly higher risk of esophageal cancer (OR 1.3, 95%CI = 0.62-3.0, P = 0.43) which was not statistically significant. NAT2 slow or fast genotypes did not affect the risk of esophageal cancer in patients with alcohol consumption or occupational exposure. These results suggest that NAT2 acetylator genotypes did not influence the susceptibility to esophageal cancer. NAT2 polymorphism did not significantly modulate the cancer risk after interaction with environmental factors like tobacco, alcohol or occupational exposure.
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Meenu
M
Jain
Shaleen
S
Kumar
Puneeta
P
Lal
Anu
A
Tiwari
U C
UC
Ghoshal
Balraj
B
Mittal
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D004777:Environment; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D008207:Lymphatic Metastasis; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human