Polymorphisms at N-acetyl
transferase 2 locus (NAT2) lead to slow, intermediate and rapid acetylation properties of the
enzyme. Improper acetylation of heterocyclic and aromatic
amines, present in tobacco, might cause
DNA adduct formation. Generally,
DNA repair enzymes remove these adduct to escape
malignancy. But, tobacco users carrying susceptible NAT2 and DNA repair loci might be at risk of
oral leukoplakia and
cancer. In this study, 389 controls, 224
leukoplakia and 310
cancer patients were genotyped at 5 polymorphic sites on NAT2 and 3 polymorphic sites on each of XRCC1 and XPD loci by PCR-RFLP method to determine the risk of the diseases. None of the SNPs on these loci independently could modify the risk of the diseases in overall population but variant genotype (Gln/Gln) at
codon 399 on XRCC1 and major genotype (
Lys/Lys) at
codon 751 on XPD were associated with increased risk of
leukoplakia and
cancer among slow acetylators, respectively (OR = 4.2, 95% CI = 1.2-15.0; OR = 1.6, 95% CI = 1.1-2.3, respectively). Variant genotype (Asn/Asn) at
codon 312 on XPD was also associated with increased risk of
cancer among rapid and intermediate acetylators (OR = 1.9, 95% CI = 1.2-2.9). Variant C-G-A haplotype at XRCC1 was associated with increased risk of
leukoplakia (OR = 1.7, 95% CI = 1.2-2.4) but
leukoplakia and
cancer in mixed tobacco users (OR = 3.1, 95% CI = 1.4-7.1, OR = 2.4, 95% CI = 1.1-5.4, respectively) among slow acetylators. Although none of the 3 loci could modulate the risk of the diseases independently but 2 loci in combination, working in 2 different biochemical pathways, could do so in these patient populations.