Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
J Gastroenterol Hepatol. 2013 Nov;28(11):1717-24. doi: 10.1111/jgh.12335.
Esophageal cancer-related gene 1 (ECRG1) is a novel tumor suppressor gene known to affect matrix remodeling, cell growth, and differentiation. Previous studies in high incidence geographical regions of esophageal cancer (EC) have shown association of ECRG1 Arg290Gln polymorphism with risk of esophageal squamous cell carcinoma (ESCC); however, role of this variant in low incidence region is missing. So, we aimed to evaluate association of ECRG1 Arg290Gln with susceptibility and prognosis of EC patients in low-risk north Indian population.
The genotyping of ECRG1 Arg290Gln polymorphism was done in 310 incident EC cases (including 179 follow up cases) and 310 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis applied were binary logistic regression for risk estimation and Kaplan-Meier/log-rank test for survival analysis. Meta-analysis of published studies, exploring role of ECRG1 polymorphism in ESCC risk, was carried out using MIX 2.0 software.
ECRG1 Arg290Gln polymorphism significantly conferred 1.8-fold increased risk of EC in dominant model (odds ratio = 1.78, 95% confidence interval = 1.27-2.49, P = 0.001). Stratification based on clinical phenotypes showed pronounced risk in cases with ESCC histopathology and middle/lower third tumor locations. No significant interaction with environmental risk factors was observed. Meta-analysis also showed significant association of ECRG1 Arg290Gln polymorphism with risk of ESCC. Kaplan-Meier and Cox regression tests suggested that ECRG1 polymorphism did not modulate survival outcome of ESCC patients.
ECRG1 Arg290Gln polymorphism significantly affects the susceptibility but not the prognosis of ESCC patients in low-risk north Indian population.
食管癌相关基因 1（ECRG1）是一种新型的肿瘤抑制基因，已知其影响基质重塑、细胞生长和分化。在食管癌高发地区的既往研究中，已显示 ECRG1 Arg290Gln 多态性与食管鳞状细胞癌（ESCC）的风险相关；然而，在低发地区，该变异体的作用尚不清楚。因此，我们旨在评估 ECRG1 Arg290Gln 多态性与印度北部低危人群中 EC 患者易感性和预后的关系。
通过聚合酶链反应-限制性片段长度多态性，在 310 例新发 EC 病例（包括 179 例随访病例）和 310 例健康对照中对 ECRG1 Arg290Gln 多态性进行了基因分型。应用二项逻辑回归进行风险估计，Kaplan-Meier/log-rank 检验进行生存分析。使用 MIX 2.0 软件对已发表的研究进行了荟萃分析，以探讨 ECRG1 多态性在 ESCC 风险中的作用。
ECRG1 Arg290Gln 多态性在显性模型中显著增加了 EC 的发病风险，比值比为 1.80（95%置信区间为 1.27-2.49，P=0.001）。基于临床表型的分层分析显示，在 ESCC 组织病理学和中/下段肿瘤位置的病例中风险显著增加。未观察到与环境危险因素的显著相互作用。荟萃分析还显示 ECRG1 Arg290Gln 多态性与 ESCC 的风险显著相关。Kaplan-Meier 和 Cox 回归检验表明，ECRG1 多态性不会影响 ESCC 患者的生存结局。
在印度北部低危人群中，ECRG1 Arg290Gln 多态性显著影响 ESCC 患者的易感性，但不影响其预后。
