Ji Xuemei, Zhang Weidong, Gui Jiang, Fan Xia, Zhang Weiwei, Li Yafang, An Guangyu, Zhu Dakai, Hu Qiang
Department of Radiation Oncology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States of America.
Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.
PLoS One. 2014 Oct 20;9(10):e109036. doi: 10.1371/journal.pone.0109036. eCollection 2014.
The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).
In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and alcohol consumption. Univariate and multivariate logistic regression analyses were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI).
We found that individuals with CHRNA5 rs3841324 combined variant genotypes (ins/del+del/del) had a >1.5-fold elevated risk for NPC than those with the ins/ins genotype (adjusted OR = 1.52; 95% CI, 1.16-2.00), especially among ever smokers (adjusted OR = 2.07; 95% CI, 1.23-3.48). The combined variant genotypes acted jointly with cigarette smoking to contribute to a 4.35-fold increased NPC risk (adjusted OR = 4.35; 95% CI, 2.57-7.38). There was a dose-response relationship between deletion alleles and NPC susceptibility (trend test, P = 0.011).
Our results suggest that genetic variants on the 15q25.1 lung cancer susceptibility locus may influence susceptibility to NPC, particularly for smoking-associated NPC. Such work may be helpful to facilitate an understanding of the etiology of smoking-associated cancers and improve prevention efforts.
包含 CHRNA5 的 15q25.1 肺癌易感基因座可改变肺癌易感性及多种与吸烟相关的表型。然而，除肺癌外，尚无研究调查与 CHRNA5 mRNA 表达关联度最高的 CHRNA5 rs3841324 与其他吸烟相关癌症风险之间的关联。在本研究中，我们检测了 rs3841324 与吸烟相关鼻咽癌（NPC）易感性之间的关联。
在这项病例对照研究中，我们对 400 例 NPC 患者和 491 例健康对照（汉族，年龄（±5 岁）、性别和饮酒量频率匹配）的 CHRNA5 rs3841324 多态性进行基因分型。采用单因素和多因素逻辑回归分析计算比值比（OR）和 95%置信区间（95%CI）。
我们发现，CHRNA5 rs3841324 组合变异基因型（ins/del+del/del）的个体患 NPC 的风险比 ins/ins 基因型个体高 1.5 倍以上（校正 OR = 1.52；95%CI，1.16 - 2.00），尤其是在曾经吸烟者中（校正 OR = 2.07；95%CI，1.23 - 3.48）。组合变异基因型与吸烟共同作用，使 NPC 风险增加 4.35 倍（校正 OR = 4.35；95%CI，2.57 - 7.38）。缺失等位基因与 NPC 易感性之间存在剂量反应关系（趋势检验，P = 0.011）。
我们的结果表明，15q25.1 肺癌易感基因座上的遗传变异可能影响 NPC 的易感性，尤其是吸烟相关的 NPC。此类研究可能有助于促进对吸烟相关癌症病因的理解并改善预防工作。
