Choudhury Javed Hussain, Choudhury Biswadeep, Kundu Sharbadeb, Ghosh Sankar Kumar
Department of Biotechnology, Assam University (A Central University), Silchar, 788011, Assam, India.
Med Oncol. 2014 Aug;31(8):67. doi: 10.1007/s12032-014-0067-8. Epub 2014 Jun 24.
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.
各种形式的烟草消费是头颈部鳞状细胞癌发生的主要风险因素之一。XRCC1和XRCC2基因的多态性可能会改变个体对烟草相关癌症的易感性。在此，我们研究了印度东北部人群中XRCC1（Arg399Gln）和XRCC2（Arg188His）多态性与烟草暴露在头颈部鳞状细胞癌进展中的相互作用。基于人群的病例对照研究包括110名头颈部鳞状细胞癌患者和140名对照。通过PCR-RFLP研究了XRCC1和XRCC2的多态性，并通过DNA测序对结果进行了验证。病例组中吸烟者和烟草-槟榔咀嚼者的比例显著更高（P = 0.045和0.033）。XRCC1 Arg399Gln的变异纯合子AA基因型和XRCC2 Arg188His的杂合子GA基因型对头颈部鳞状细胞癌的风险增加（OR分别为2.43；P = 0.031和OR 3.29；P < 0.01）。与非咀嚼者相比，烟草-槟榔咀嚼与XRCC1和XRCC2的变异基因型之间的相互作用导致头颈部鳞状细胞癌的风险增加了数倍。携带XRCC1 AA和XRCC2 GA基因型的重度吸烟者与从不吸烟者相比，患头颈部鳞状细胞癌的风险显著更高（P分别为0.017和0.003）。在基因-基因相互作用分析中，同时携带XRCC1 GA（Arg/Gln）和XRCC2 GA（Arg/His）基因型的个体患头颈部鳞状细胞癌的风险最高（P = 0.001）。我们的研究结果表明，烟草与XRCC1和XRCC2多态性的相互作用增加了头颈部鳞状细胞癌的风险。此外，这两个DNA修复基因之间的相互作用可能会调节对头颈部鳞状细胞癌的易感性。
