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Cancer Epidemiol. 2014 Feb;38(1):66-72. doi: 10.1016/j.canep.2013.12.009. Epub 2014 Jan 20.

Variants in the 5'-upstream region of GPC5 confer risk of lung cancer in never smokers.

Author information

  • 1Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
  • 2Department 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.
  • 3Department of Environmental Health, Harvard School of Public Health, Harvard University, Boston, MA, United States.
  • 4Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address: sdchen2@126.com.
  • 5Department 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. Electronic address: miaoxp@mail.hust.edu.cn.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Function prediction; GPC5; Lung cancer in never smokers; Single nucleotide polymorphism

PMID:
24456789
[PubMed - indexed for MEDLINE]
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