The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China; Guangzhou Chest Hospital, Guangzhou, P.R. China.
Mol Carcinog. 2013 Nov;52 Suppl 1:E19-27. doi: 10.1002/mc.21934. Epub 2012 Jun 12.
The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case-control studies conducted in southern and eastern Chinese, we genotyped five tagSNPs of WWOX gene (rs10220974C > T, rs3764340C > G, rs12918952G > A, rs383362G > T, and rs12828G > A) in 1,559 lung cancer cases and 1,679 controls. Logistic regression analysis showed that two tagSNPs (rs3764340C > G; rs383362G > T) were significantly associated with lung cancer risk in dominant model (rs3764340C > G, GC/GG vs. CC: adjust OR = 1.35, 95% CI = 1.11-1.65; rs383362G > T, TG + TT vs. GG: adjust OR = 1.33, 95% CI = 1.14-1.55). The haplotype analysis further shown that the haplotype "G-T" was associated with the highest increased risk of lung cancer (OR = 2.20; 95% CI = 1.43-3.37). After combined these two loci, the number of the risk genotypes was associated with increased cancer risk in a dose-response manner (Ptrend = 3.16 × 10(-6) ). In addition, a gene-based association analysis by using VEGAS software suggested the WWOX as a susceptible gene for lung cancer (P = 0.009). However, for rs10220974C > T, rs12918952G > A, and rs12828G > A, no significant association was observed for lung cancer risk. Taken together, our data suggested that genetic variants in WWOX may be genetic biomarkers for susceptibility to lung cancer.
WW 结构域包含的氧化还原酶（WWOX）基因是一个已被确定的肿瘤抑制基因，已有多项研究报道其单核苷酸多态性与癌症易感性相关。我们假设 WWOX 的遗传变异与肺癌风险相关。在南方和东方的两个独立病例对照研究中，我们对 WWOX 基因的五个标签单核苷酸多态性（rs10220974C > T、rs3764340C > G、rs12918952G > A、rs383362G > T 和 rs12828G > A）在 1559 例肺癌病例和 1679 例对照中进行了基因分型。逻辑回归分析显示，两个标签单核苷酸多态性（rs3764340C > G；rs383362G > T）在显性模型中与肺癌风险显著相关（rs3764340C > G，GC/GG 与 CC：调整 OR = 1.35，95%CI = 1.11-1.65；rs383362G > T，TG + TT 与 GG：调整 OR = 1.33，95%CI = 1.14-1.55）。单体型分析进一步显示，单体型“G-T”与肺癌的最高风险增加相关（OR = 2.20；95%CI = 1.43-3.37）。结合这两个位点后，风险基因型的数量与癌症风险呈剂量-反应关系增加（Ptrend = 3.16 × 10(-6)）。此外，使用 VEGAS 软件进行的基于基因的关联分析表明，WWOX 是肺癌的易感基因（P = 0.009）。然而，对于 rs10220974C > T、rs12918952G > A 和 rs12828G > A，未观察到与肺癌风险相关的显著关联。总之，我们的数据表明，WWOX 中的遗传变异可能是肺癌易感性的遗传生物标志物。
