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.
abstract: 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.
authors: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
authors: Pinaki
authors: P
authors: Mondal
authors: Sayantan
authors: S
authors: Datta
authors: Guru Prasad
authors: GP
authors: Maiti
authors: Aradhita
authors: A
authors: Baral
authors: Ganga Nath
authors: GN
authors: Jha
authors: Chinmay Kumar
authors: CK
authors: Panda
authors: Shantanu
authors: S
authors: Chowdhury
authors: Saurabh
authors: S
authors: Ghosh
authors: Bidyut
authors: B
authors: Roy
authors: Susanta
authors: S
authors: Roychoudhury
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007971:Leukoplakia / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult