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Comprehensive SNP Scan of DNA Repair and DNA Damage Response Genes Reveal Multiple Susceptibility Loci Conferring Risk to Tobacco Associated Leukoplakia and Oral Cancer

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Title Comprehensive SNP Scan of DNA Repair and DNA
Damage Response Genes Reveal Multiple Susceptibility
Loci Conferring Risk to Tobacco Associated Leukoplakia
and Oral Cancer
 
Creator Mondal, Pinaki
Datta, Sayantan
Maiti, Guru Prasad
Baral, Aradhita
Jha, Ganga Nath
Panda, ChinmayKumar
Chowdhury, Shantanu
Ghosh, Saurabh
Roy, Bidyut
Roychoudhury, Susanta
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description Polymorphic variants of DNA repair and damage response genes play major role in carcinogenesis. These variants are
suspected as predisposition factors to Oral Squamous Cell Carcinoma (OSCC). For identification of susceptible variants
affecting OSCC development in Indian population, the ‘‘maximally informative’’ method of SNP selection from HapMap data
to non-HapMap populations was applied. Three hundred twenty-five SNPs from 11 key genes involved in double strand
break repair, mismatch repair and DNA damage response pathways were genotyped on a total of 373 OSCC, 253
leukoplakia and 535 unrelated control individuals. The significantly associated SNPs were validated in an additional cohort
of 144 OSCC patients and 160 controls. The rs12515548 of MSH3 showed significant association with OSCC both in the
discovery and validation phases (discovery P-value: 1.43E-05, replication P-value: 4.84E-03). Two SNPs (rs12360870 of
MRE11A, P-value: 2.37E-07 and rs7003908 of PRKDC, P-value: 7.99E-05) were found to be significantly associated only with
leukoplakia. Stratification of subjects based on amount of tobacco consumption identified SNPs that were associated with
either high or low tobacco exposed group. The study reveals a synergism between associated SNPs and lifestyle factors in
predisposition to OSCC and leukoplakia.
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1935/1/PLOS_ONE___8_(_2_)____Article_Number_e56952;2013[72].pdf
Mondal, Pinaki and Datta, Sayantan and Maiti, Guru Prasad and Baral, Aradhita and Jha, Ganga Nath and Panda, ChinmayKumar and Chowdhury, Shantanu and Ghosh, Saurabh and Roy, Bidyut and Roychoudhury, Susanta (2013) Comprehensive SNP Scan of DNA Repair and DNA Damage Response Genes Reveal Multiple Susceptibility Loci Conferring Risk to Tobacco Associated Leukoplakia and Oral Cancer. PLOS ONE, 8 (2). e56952.
 
Relation http://dx.doi.org/10.1371/journal.pone.0056952
http://www.eprints.iicb.res.in/1935/