Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow 226014, India.
Mol Biol Rep. 2012 Feb;39(2):1153-62. doi: 10.1007/s11033-011-0844-9. Epub 2011 May 15.
Genetic variants in p53 and in its homologue p73 may modulate Esophageal Cancer (EC) risk because they are supposed to influence cell cycle progression, apoptosis and DNA repair. Therefore, we aimed to evaluate the association of p53 intron3 16 bp duplication and p73 G4C14-to-A4T14 polymorphisms with susceptibility to EC in a northern Indian population in 255 EC patients and 255 age and sex matched healthy controls. We found that p53 intron3 16 bp duplication polymorphism was not associated with EC and its clinical characteristics. However, p73 G4C14-to-A4T14 polymorphism was associated with significant higher risk of EC (OR = 1.74, 95% CI = 1.16-2.60, P = 0.007) in an allele dose-dependent manner (P(trend) = 0.0047). Stratification of subjects on the basis of clinical characteristics showed that p73 AT genotype carriers were at significant increased risk of developing esophageal squamous cell carcinoma (OR = 1.78, 95% CI = 1.18-2.67, P = 0.006) at middle third tumor location (OR = 1.87, 95% CI = 1.18-2.97, P = 0.007) with lymph node metastasis (OR = 1.77, 95% CI = 1.04-3.02, P = 0.035). No interaction with environmental risk factors was observed with any of the studied polymorphisms. In summary, p73 G4C14-to-A4T14 polymorphism but not the p53 intron3 16 bp duplication polymorphism is associated with EC and its clinical characteristics in northern Indian population.
p53 和其同源物 p73 中的遗传变异可能调节食管癌 (EC) 风险,因为它们被认为会影响细胞周期进程、细胞凋亡和 DNA 修复。因此,我们旨在评估 p53 内含子 3 16 bp 重复和 p73 G4C14-to-A4T14 多态性与北印度人群中 255 例 EC 患者和 255 例年龄和性别匹配的健康对照者易感性的关系。我们发现,p53 内含子 3 16 bp 重复多态性与 EC 及其临床特征无关。然而,p73 G4C14-to-A4T14 多态性与 EC 的显著更高风险相关(OR = 1.74,95%CI = 1.16-2.60,P = 0.007),呈等位基因剂量依赖性(P(trend) = 0.0047)。基于临床特征对受试者进行分层显示,p73 AT 基因型携带者在中段肿瘤位置(OR = 1.78,95%CI = 1.18-2.67,P = 0.006)和有淋巴结转移(OR = 1.77,95%CI = 1.04-3.02,P = 0.035)的食管鳞癌发生风险显著增加。未观察到任何研究多态性与环境危险因素之间存在交互作用。总之,p73 G4C14-to-A4T14 多态性而非 p53 内含子 3 16 bp 重复多态性与北印度人群中的 EC 及其临床特征相关。