Gastric Cancer Risk and XPD/ERCC2 SNPS (LYS751GLN, ASP312ASN) Gene Polymorphism—An Experimental Study in Kashmir Valley of India

ERCC2/XPD, is one of the core genes involved in transcriptioncoupled NER pathway (a fundamental defense mechanism against the carcinogenic effects of sunlight and certain genetic defects in the DNA repair pathways); and its functional polymorphisms may be associated with the risk of different types of cancers. The present investigation includes Lys751Gln & Asp312Asn polymorphisms in a case-control hospital based study in 100 Kashmiri GC patients &100 age & sex matched controls. It was observed that most of the cases were males, numbering 72 with a maximum number falling in the age group of 56-65 years; whereas female GC cases were only 28 with a maximum number in the age group of 56-65 years as in the males. The male GC cases were all smokers especially hooka smokers. All female cases were non-smokers. Statistically significant results were observed in GC cases who were smokers with a pvalue of <0.0001; χ2 =63.15; O.R. =7.427 and 3.919to 14.081 of 95%C.I., suggesting a strong correlation between smoking and the risk of GC. Among the dietary factors the intake of salt tea that was consumed by both the GC cases as well controls was found to be statistically insignificant (Fishers exact test =0.134; O.R. =1.644 and 95% C.I. = 0.90 to 2.976). Statistically significant values were found in GC cases who included preserved dried foods in their diet. (Fishers exact test = <0.0001; O.R. = 11.643; and 95% C.I. =5.542 to 24.46). The intake of too much of spices and chillies in the diet of GC cases was also found to be statistically significant. (Fishers exact test =0.007; O.R. = 2.257 and 95% C.I. = 1.28 to 3.979) suggesting the role of these dietary foods in the GC risk. Family 1 Corresponding author: [email protected] R. Ashraf, S. A. Kadla, H. A. Wani, A. A. Bhat, S. Majid : Gastric Cancer Risk and XPD/ERCC2 SNPS (LYS751GLN, ASP312ASN) Gene Polymorphism—An Experimental Study in Kashmir Valley of India EUROPEAN ACADEMIC RESEARCHVol.II, Issue 11/February 2015 14147 history of carcinogenesis although found in the small number of GC cases and none in the control group was moderately statistically significant. (Fishers exact test =0.029). The genotypic frequencies of ERCC2codon 751 showed a significant difference between cases and controls ((χ2 =16.85 p≤0.0001)). Allelic frequencies revealed statistically significant excess of Gln allele in cases as compared to controls and a low percentage of Lys allele in cases as compared in controls (Fishers exact test = ≤0.0001, OR =0.213, 95% CI 0.106 to 0.426). The codon 312 of ERCC2 studied also showed statistically significant genotypic frequencies between cases and controls (χ2 8.75 p value of 0.013). Allelic frequencies revealed statistically significant excess of Asn allele in cases as compared to controls and a low percentage of Asp allele in cases as compared in controls (Fishers exact test = 0.001, O.R = 0.384, 95% C.I = 0.218 to 0.675). The magnitude and statistical significance of Asp312Asn polymorphism was smaller and weaker than the Lys751Gln polymorphism studied in the present study of GC cases vs controls. Abbreviations: ERCC –excision repair cross-complementing rodent repair deficiency; XPDxeroderma pigmentosum group D; GCgastric cancer; SNP-single nucleotide polymorphism; GMC government medical college Srinagar Kashmir; NIMSNational institute of medical sciences Rajasthan.