Combined effect of tobacco and DNA repair genes polymorphisms of XRCC1 and XRCC2 influence high risk of head and neck squamous cell carcinoma in northeast Indian population

Abstract

Tobacco consumption in various forms is one of the major risk factor for the development of head and neck squamous cell carcinoma. Polymorphisms in XRCC1 and XRCC2 genes may alter an individual's susceptibility to tobacco-related cancers. Here, we have investigated the interaction of XRCC1 (Arg399Gln) and XRCC2 (Arg188His) polymorphism and tobacco exposure in the progression of HNSCC in northeast Indian population. The population-based case-control study includes 110 HNSCC patients and 140 controls. The polymorphisms of XRCC1 and XRCC2 were studied by means of PCR-RFLP, and the results were confirmed by DNA sequencing. Smokers and tobacco-betel quid chewers were significantly higher in cases (P = 0.045 and 0.033). The variant homozygote AA genotype of XRCC1 Arg399Gln and heterozygote GA genotype of XRCC2 Arg188His has an increased risk toward HNSCC (OR 2.43; P = 0.031 and OR 3.29; P < 0.01, respectively). The interaction between tobacco-betel quid chewing and variant genotypes of XRCC1 and XRCC2 resulted in several fold increase the risk of HNSCC, when compared to non-chewers. Heavy smokers carrying XRCC1 AA and XRCC2 GA genotypes had a significantly higher risk of HNSCC compared to never smokers (P = 0.017 and 0.003, respectively). Upon gene-gene interaction analysis, individuals carrying both XRCC1 GA (Arg/Gln) and XRCC2 GA (Arg/His) genotypes had the highest risk of HNSCC (P = 0.001).Our finding suggests that interaction of tobacco and polymorphisms of XRCC1 and XRCC2 increases the risk of HNSCC. Furthermore, cross talk between these two DNA repair genes might modulate susceptibility toward HNSCC.

Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

“…We also found no association of XRCC1 c.839G>A and c.1196G>A SNPs with OPSCC risk, according to previous results from overall HNSCC studies (Sturgis et al 1999;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Li et al 2007;Harth et al 2008;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;Al-Hadyan et al 2012;Yuan et al 2012). In contrast, the variant allele A of c.1196G>A SNP was associated with decreased risk (Olshan et al 2002;Kumar et al 2012;Khlifi et al 2014) and increased risk (Choudhury et al 2014) of overall HNSCC. The disparate results obtained in our study and previous studies may be, again, attributed to different HN tumor sites investigated in previous studies, since similar frequencies of the genotypes were seen in our control group and in the other controls.…”

“…The roles of the OGG1 c.977C>G (Elahi et al 2002;Zhang et al 2004;Matullo et al 2006;Görgens et al 2007;Hall et al 2007;Kumar et al 2011;Mitra et al 2011), APEX1 c.444T>G (Matullo et al 2006;Li et al 2007); XRCC1 c.-77T>C, c.580C>T (Sturgis et al 1999;Olshan et al 2002;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;Kumar et al 2012), c.839G>A (Tae et al 2004;Applebaum et al 2009;Gugatschka et al 2011;Kumar et al 2012) and c.1196G>A (Sturgis et al 1999;Olshan et al 2002;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Li et al 2007;Harth et al 2008;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;AlHadyan et al 2012;Kumar et al 2012;Yuan et al 2012;Choudhury et al 2014;Khlifi et al 2014) SNPs in overall HNSCC risk are still controversial or unknown.…”

<p>Association of <em>XRCC1</em>, <em>XRCC2</em> and <em>XRCC3</em> Gene Polymorphism with Esophageal Cancer Risk</p>

“…Similar results were reported in three other studies from North India on head and neck cancer, 45 hepatocellular carcinoma 46 and lung cancer. 47 Contrary to the results of the present study, some previous studies from North India have reported an increased risk with AA genotype of XRCC1p.Arg399Gln polymorphism in lung cancer, 48 head and neck cancer, 49 colorectal cancer 50 and prostate cancer. 51 Similarly, some studies from South India reported an association of increased risk with the AA genotype in gastric cancer, 52 colorectal cancer, 29 lung cancer, 53,54 cervical cancer, 55 Naso-pharyngeal cancer, 56 acute lymphoblastic leukemia 57 and acute myeloid leukemia.…”

Influence of the CYP1A1 T3801C Polymorphism on Tobacco and Alcohol-Associated Head and Neck Cancer Susceptibility in Northeast India

“…Epidemiological studies from the northeast India reported tobacco smoking as one of the strongest risk factor for HNC (Yadav et al, 2010;Talukdar et al, 2013;Choudhury and Ghosh, 2014;Ghosh et al, 2014a) . Moreover, it was seen that tobacco-betel quid chewing also had a very high impact on HNC risk (Sharan et al, 2012;Choudhury et al, 2014) . Tobacco in any form generates free radicals that deplete antioxidants and cause oxidative damage to DNA, proteins and lipids resulting in cancers.…”