Role of NQO1 609C>T and NQO2 -3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis
Role of NQO1 609C>T and NQO2 -3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis
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DOI：
10.1007/s11033-012-1781-y
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发表时间：
2012-09-01
影响因子：
2.8
通讯作者：
Mittal, Balraj
中科院分区：
文献类型：
--
作者：
Malik, Manzoor Ahmad;Zargar, Showkat Ali;Mittal, Balraj
食管癌（EC）是一种复杂的多因素疾病，环境和遗传因素在其中起主要作用。NADPH：醌氧化还原酶1（NQO1）和NRH：醌氧化还原酶2（NQO2）是Ⅱ相胞质酶，可催化醌的代谢，在环境致癌物的解毒过程中起重要作用。在印度克什米尔地区的135例食管癌患者和195例无亲缘关系的健康对照中，采用聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）方法进行了一项病例对照研究，以探讨NQO1 609C>T和NQO2 -3423G>A多态性与食管癌易感性的关联。我们还对9项已发表的关于NQO1 609C>T的研究（1224例病例和1740例对照）进行了荟萃分析，并评估了NQO1 609C>T多态性与食管癌风险之间的关联。观察到食管癌病例组和相应对照组之间NQO1 609C>T和NQO2 -3423G>A基因型分布存在显著差异（比值比分别为2.65；95%置信区间为1.29 - 5.42和1.88；95%置信区间为1.02 - 3.49）。此外，基因 - 基因相互作用显示，NQO1 609C>T和NQO2 -3423G>A多态性的变异基因型使食管腺癌的风险显著增加，并且与环境危险因素的相互作用表明，在克什米尔山谷高盐茶饮用者中，NQO1 609C>T的TT基因型患食管癌的风险显著增加（比值比 = 3.72，95%置信区间 = 0.98 - 14.19）。对NQO1 609C>T多态性的荟萃分析也表明，该多态性与亚洲人以及欧洲人的食管癌有关。总之，NQO1 609C>T和NQO2 -3423G>A基因变异调节克什米尔高危人群患食管癌的风险。
Esophageal cancer (EC) is a complex multifactorial disorder, where environmental and genetic factors play major role. NADPH:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are phase II cytosolic enzymes that catalyze metabolism of quinones, important in the detoxification of environmental carcinogens. A case-control study was performed to investigated the associations of NQO1 609C > T and NQO2 -3423G > A polymorphisms with susceptibility to EC in a high-risk Kashmiri population of India in 135 EC patients and 195 unrelated healthy controls using PCR-RFLP. We also performed a meta analysis of nine published studies (1,224 cases and 1,740 controls) on NQO1 609C > T and evaluated the association between the NQO1 609C > T polymorphisms and esophageal cancer risk. A significant difference in NQO1 609C > T and NQO2 -3423G > A genotype distribution between EC cases and corresponding controls groups was observed (OR = 2.65; 95 % CI = 1.29-5.42 and OR = 1.88; 95 % CI = 1.02-3.49 respectively). Further, gene-gene interaction showed significantly increased risk for esophageal adenocarcinoma with variant genotypes of NQO1 609C > T and NQO2 -3423G > A polymorphisms and interaction with environmental risk factors revealed pronounced risk of EC with NQO1 609C > T TT genotype in high salted tea users of Kashmir valley (OR = 3.72, 95 % CI = 0.98-14.19). Meta analysis of NQO 609C > T polymorphism also suggested association of the polymorphism with EC in Asians as well as Europeans. In conclusion, NQO1 609C > T and NQO2 -3423G > A genetic variations modulate risk of EC in high-risk Kashmir population.