Department of Radiation Oncology, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.
PLoS One. 2013 Nov 19;8(11):e76372. doi: 10.1371/journal.pone.0076372. eCollection 2013.
A common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians. In addition, many studies have investigated the role of this polymorphism in the etiology of cancer of various organs. Nevertheless, the results of related case-control studies remain inconsistent.
We hypothesized that the genetic risk variant identified in Caucasians may potentially influence the susceptibility to lung cancer in the Chinese population. To test this hypothesis, a case-control study including 539 non-small-cell lung cancer (NSCLC) cases and 627 cancer-free controls was conducted. Furthermore, to investigate the association between rs2736098 and cancer risk, a meta-analysis based on previously published studies and our case-control study was also performed.
Multivariate logistic regression demonstrated that individuals carrying the A allele or the AA genotype exhibited a significantly elevated risk of NSCLC compared with those carrying the G allele or GG genotype (A vs. G: OR = 1.21, 95% CI = 1.02-1.43, P = 0.028; AA vs. GG: OR = 1.48, 95% CI = 1.05-2.09, P = 0.025). Additionally, this association was stronger among adenocarcinoma cases (AA vs. GG: OR = 1.67, 95% CI = 1.12-2.50, P = 0.013; A vs. G: OR = 1.28, 95% CI = 1.05-1.57, P = 0.016). In the meta-analysis, a borderline significant association between the rs2736098 polymorphism and overall cancer risk was observed (AA vs. GG: OR = 1.25, 95% CI = 1.07-1.46; AA vs. AG+GG: OR = 1.22, 95% CI = 1.06-1.41; additive model: OR = 1.10, 95% CI = 1.02-1.18), and further stratifications demonstrated a moderately increased risk for lung and bladder cancer, Asian ethnicity and hospital-based studies.
Our results suggest that the rs2736098 polymorphism may contribute to the risk of lung cancer, especially adenocarcinoma, in the Chinese population. In addition, the current meta-analysis indicates that this genetic variant is only weakly associated with overall cancer risk. However, the rs2736098 polymorphism may affect individual susceptibility to lung and bladder cancer. Further studies are needed to validate our findings.
最近有研究报道,端粒酶逆转录酶(TERT)rs2736098 这一常见的遗传变异与高加索人群的肺癌风险相关。此外,许多研究已经探讨了这种多态性在不同器官癌症发病机制中的作用。然而,相关病例对照研究的结果仍然不一致。
我们假设在高加索人群中发现的遗传风险变异可能会影响中国人患肺癌的易感性。为了验证这一假设,进行了一项包括 539 例非小细胞肺癌(NSCLC)病例和 627 例无癌对照的病例对照研究。此外,还进行了一项荟萃分析,基于先前发表的研究和我们的病例对照研究,以探讨 rs2736098 与癌症风险之间的关联。
多变量 logistic 回归表明,与携带 G 等位基因或 GG 基因型的个体相比,携带 A 等位基因或 AA 基因型的个体患 NSCLC 的风险显著升高(A 等位基因比 G 等位基因:OR=1.21,95%CI=1.02-1.43,P=0.028;AA 基因型比 GG 基因型:OR=1.48,95%CI=1.05-2.09,P=0.025)。此外,这种关联在腺癌病例中更强(AA 基因型比 GG 基因型:OR=1.67,95%CI=1.12-2.50,P=0.013;A 等位基因比 G 等位基因:OR=1.28,95%CI=1.05-1.57,P=0.016)。荟萃分析显示,rs2736098 多态性与总体癌症风险之间存在边缘显著关联(AA 基因型比 GG 基因型:OR=1.25,95%CI=1.07-1.46;AA 基因型比 AG+GG 基因型:OR=1.22,95%CI=1.06-1.41;加性模型:OR=1.10,95%CI=1.02-1.18),进一步分层分析表明,该遗传变异与肺癌和膀胱癌、亚洲人种和基于医院的研究中度相关。
我们的研究结果表明,rs2736098 多态性可能导致中国人患肺癌的风险增加,尤其是腺癌。此外,目前的荟萃分析表明,这种遗传变异与总体癌症风险仅有微弱关联。然而,rs2736098 多态性可能影响个体患肺癌和膀胱癌的易感性。需要进一步的研究来验证我们的发现。