Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Epidemiol. 2014 Feb;38(1):66-72. doi: 10.1016/j.canep.2013.12.009. Epub 2014 Jan 20.
A recent genome-wide study (GWAS) has identified GPC5 as a promising susceptibility gene for Lung cancer in never smokers (LCINS). However, the most significant single nucleotide polymorphism (SNP) in this GWAS, rs2352028, has yielded controversial results. The aim of this study was to clarify the relationship between rs2352028 and LCINS. Considering that rs2352028 might be largely marker-SNP correlated to causative variants, two predicted functional SNPs, rs3759452 and rs7322083, were additionally investigated in this study.
A hospital based case-control study including 298 cases and 599 controls in a never-smoking Chinese Han population was conducted, and then a meta-analysis combining our data and published data was performed to verify the findings.
The SNP rs3759452, predicted to potentially change transcription factor binding site of GPC5, was significantly associated with LCINS risk (odds ratio for dominant model=1.55, 95% confidence interval=1.14-2.12). Nevertheless, no significant evidence was showed for rs2352028, both in our case-control study and the meta-analysis including 13 studies of 2342 LCINS cases and 13,398 never-smoking controls. Further subgroup meta-analysis according to population ethnicity and cancer histology also reported no significant association of rs2352028.
The association conferring rs3759452 further supports the value of GPC5 in susceptibility to LCINS. Nevertheless, comprehensive analyses are warranted to dissect the functional mechanism underpinning rs3759452.
最近的一项全基因组研究（GWAS）发现 GPC5 是从不吸烟的肺癌（LCINS）的一个有前途的易感基因。然而，这项 GWAS 中最显著的单核苷酸多态性（SNP）rs2352028 产生了有争议的结果。本研究旨在阐明 rs2352028 与 LCINS 的关系。考虑到 rs2352028 可能与致病变异体有很大的标记 SNP 相关性，本研究还额外研究了两个预测的功能 SNP rs3759452 和 rs7322083。
在一个从不吸烟的中国汉族人群中进行了一项基于医院的病例对照研究，包括 298 例病例和 599 例对照，然后进行了一项荟萃分析，结合我们的数据和已发表的数据来验证这些发现。
SNP rs3759452 预测可能改变 GPC5 的转录因子结合位点，与 LCINS 风险显著相关（优势比显性模型=1.55，95%置信区间=1.14-2.12）。然而，无论是在我们的病例对照研究中，还是在包括 13 项研究的 2342 例 LCINS 病例和 13398 例从不吸烟对照的荟萃分析中，rs2352028 均未显示出显著证据。根据人群种族和癌症组织学进行的进一步亚组荟萃分析也没有报告 rs2352028 与 LCINS 之间存在显著关联。
rs3759452 赋予的关联进一步支持了 GPC5 在 LCINS 易感性中的价值。然而，需要进行综合分析来剖析 rs3759452 背后的功能机制。
