International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants
International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants
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DOI：
10.1093/carcin/bgq001
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发表时间：
2010-04-01
期刊：
影响因子：
4.7
通讯作者：
Hung, Rayjean J.
中科院分区：
文献类型：
--
作者：
Truong, Therese;Sauter, Wiebke;Hung, Rayjean J.
背景。在个别研究中对候选基因的分析在确定与肺癌风险确切相关的特定基因变异方面仅取得了有限的成功。在国际肺癌联盟（ILCCO）中，我们对10个常见变异进行了一项协调的基因分型研究，因为它们与肺癌有关联的先前证据而被选中。这些变异属于来自不同癌症相关途径的候选基因，包括炎症（IL1B）、叶酸代谢（MTHFR）、调节功能（AKAP9和CAMKK1）、细胞粘附（SEZL6）和凋亡（FAS、FASL、TP53、TP53BP1和BAT3）。方法。来自15个ILCCO病例对照研究的基因型数据来自8431例肺癌病例和11072例欧洲血统和亚洲种族人群的对照。使用无条件逻辑回归对每个变异与肺癌风险之间的关联进行建模。结果。只有TP53BP1的非同音变体（rs560191）与肺癌风险之间存在显著相关性（OR = 0.91, P = 0.002）。这种相关性在鳞状细胞癌中更为显著（OR = 0.86, P = 6 × 10(-4)）。没有观察到中心、种族、吸烟状况、年龄组或性别的异质性。为了证实这种关联，我们纳入了一组独立研究（9966例/11 722例对照）中该变异的结果，我们报告了类似的结果。当将所有这些研究合并在一起时，我们报告的总体OR = 0.93 (0.89-0.97) （P = 0.001）。这种相关性仅在鳞状细胞癌中有统计学意义[OR = 0.89 (0.85-0.95), P = 1 × 10(-4)]。结论。本研究提示rs560191与肺癌风险相关，并进一步强调了联合体在复制或反驳已发表的遗传关联方面的价值。
Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case-control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 x 10(-4)). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89-0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85-0.95), P = 1 x 10(-4)]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations.