Ghosh Soumee, Ghosh Sudakshina, Bankura Biswabandhu, Saha Makhan Lal, Maji Suvendu, Ghatak Souvik, Pattanayak Arup Kumar, Sadhukhan Susanta, Guha Manalee, Nachimuthu Senthil Kumar, Panda Chinmay Kumar, Maity Biswanath, Das Madhusudan
Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India.
Department of Surgery, Institute of Post Graduate Medical Education & Research, 244 A.J.C Bose Road, Kolkata, 700 020, West Bengal, India.
Tumour Biol. 2016 Jul;37(7):9139-49. doi: 10.1007/s13277-015-4780-5. Epub 2016 Jan 14.
Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95 % confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95 % CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95 % CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95 % CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.
胃癌是印度最常见的恶性肿瘤之一。最近研究表明，DNA修复基因或外源性物质代谢途径基因多态性会影响个体对胃癌的易感性。在此，我们评估了X射线修复交叉互补基因1（XRCC1）和谷胱甘肽S-转移酶（GST）基因（GSTM1、GSTT1和GSTP1）的常见多态性、吸烟、饮酒与胃癌患者总生存期之间可能存在的相互作用。在这项基于人群的病例对照研究中，纳入了70例胃癌患者和82例健康对照。通过标准问卷收集流行病学数据，并采集每个个体的血样。采用聚合酶链反应和直接DNA测序法检测XRCC1基因的Arg194Trp、Arg280His和Arg399Gln多态性。分别采用多重聚合酶链反应和限制性片段长度多态性（RFLP）法鉴定GSTM1和GSTT1基因的无效多态性以及GSTP1基因的Ile105Val多态性。携带XRCC1基因Arg/Gln +Gln/Gln基因型（p = 0.031；比值比= 2.32；95%置信区间（CI）1.07 - 5.06）和GSTP1基因Val/Val基因型（p = 0.009；比值比= 8.64；95% CI 1.84 - 40.55）的个体患胃癌的风险显著升高。在携带GSTP1基因Ile/Val +Val/Val基因型的吸烟者和饮酒者中观察到胃癌风险升高（p = 0.041；比值比= 3.71；95% CI 0.98 - 14.12；p = 0.002；比值比= 12.31；95% CI 1.71 - 88.59）。这些研究结果表明，XRCC1基因的rs25487和GSTP1基因的rsl695可被视为与胃癌相关的危险因素，并可能用作评估该疾病易感性的分子标志物。
