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Association of XRCC1, XRCC3, and NAT2 Polymorphisms with the Risk of Oral Submucous Fibrosis among Eastern Indian Population

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Title Association of XRCC1, XRCC3, and NAT2 Polymorphisms
with the Risk of Oral Submucous Fibrosis among Eastern
Indian Population
 
Creator Mukherjee, Sanjit
Das Bhowmik, Aneek
Roychoudhury, Paromita
Mukhopadhyay, Kanchan
Ray, Jay Gopal
Chaudhuri, Keya
 
Subject Molecular & Human Genetics
 
Description 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.
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.
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.
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.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1518/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY_287(_14)11546%2D11555;2012[36].pdf
Mukherjee, Sanjit and Das Bhowmik, Aneek and Roychoudhury, Paromita and Mukhopadhyay, Kanchan and Ray, Jay Gopal and Chaudhuri, Keya (2012) Association of XRCC1, XRCC3, and NAT2 Polymorphisms with the Risk of Oral Submucous Fibrosis among Eastern Indian Population. Journal of Oral Pathology & Medicine , 41 (4). pp. 292-302.
 
Relation http://dx.doi.org/10.1111/j.1600-0714.2011.01097.x
http://www.eprints.iicb.res.in/1518/