title: Association of XRCC1, XRCC3, and NAT2 polymorphisms with the risk of oral submucous fibrosis among eastern Indian population.
abstract: BACKGROUND
  Arecanut and smokeless tobacco usage is a major cause for oral submucous fibrosis (OSF) and its subsequent development to oral squamous cell carcinoma in South-east Asian population. Polymorphisms at N-acetyltransferase 2 locus, coding for an enzyme catalyzing acetylation of aromatic amines, might cause DNA adduct formation because of improper acetylation of these polyaromatic hydrocarbons. DNA repair enzymes remove these adduct to prevent malignancy.
  
  
  METHODS
  In this hospital-based study, 100 controls and 88 OSF patients were genotyped at four polymorphic sites on NAT2 481 (C > T; silent), 590 (G > A; Arg197 > Gln), 803 (A > G; Lys268 > Arg), 857 (G > A; Gly286 > Glu) and two on XRCC1 18067 (C > T Arg 194 > Trp), 28152 (G > A Arg 399 > Gln), and one of XRCC3 26304 (C > T Thr 241 > Met) loci by PCR-RFLP to determine the risk of the disease.
  
  
  RESULTS
  Heterozygous XRCC3 codon 241 [OR 2.07 (1.05-4.06)], homozygous variant of NAT C481T [OR 2.81 (1.09-7.21)], and both heterozygous and homozygous variants of NAT codon 268 and 286 [OR 2.31 (1.20-4.45) and 4.98 (1.87-13.14), and 6.12 (2.75-13.62) and 2.65 (1.04-6.72)] individually influenced susceptibility to OSF in the population.
  
  
  CONCLUSIONS
  Gene-gene interaction analysis by multifactor dimensionality reduction (MDR) revealed that XRCC3 Thr 241 Met had the largest univariate effect followed by XRCC3 Thr 241 Met - NAT2 A857G in men that presents a highly synergistic interaction as one of the potential combinations of single nucleotide polymorphisms (SNPs) to increase the risk of OSF in men if exposed to arecanut or smokeless tobacco usage. These observations can speculate the impact of the studied SNPs on the etiology of OSF.
authors.affiliation: Molecular & Human Genetics Division, Indian Institute of Chemical Biology (A Unit of CSIR), Kolkata, India.
authors.forename: Sanjit
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Aneek Das
authors.initials: AD
authors.lastname: Bhowmik
authors.forename: Paromita
authors.initials: P
authors.lastname: Roychoudhury
authors.forename: Kanchan
authors.initials: K
authors.lastname: Mukhopadhyay
authors.forename: Jay Gopal
authors.initials: JG
authors.lastname: Ray
authors.forename: Keya
authors.initials: K
authors.lastname: Chaudhuri
mesh_terms: D000328:Adult; D001114:Areca / Q000009:adverse effects; D001120:Arginine / Q000235:genetics; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India; D008239:Lysine / Q000235:genetics; D008297:Male; D008715:Methionine / Q000235:genetics; D058011:Multifactor Dimensionality Reduction; D009914:Oral Submucous Fibrosis / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D013912:Threonine / Q000235:genetics; D014030:Tobacco, Smokeless / Q000009:adverse effects; D014364:Tryptophan / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D005973:Glutamine; D013912:Threonine; D018698:Glutamic Acid; D014364:Tryptophan; D001120:Arginine; D008715:Methionine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D008239:Lysine; D005998:Glycine