Variants in the 5'-upstream region of GPC5 confer risk of lung cancer in never smokers.
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.
Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Li
L
Liu
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.
Rong
R
Zhong
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.
Li
L
Zou
Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Jinjian
J
Fu
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.
Beibei
B
Zhu
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.
Wei
W
Chen
Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Xiaohua
X
Ye
Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Yanhui
Y
Gao
Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Yi
Y
Yang
Department of Environmental Health, Harvard School of Public Health, Harvard University, Boston, MA, United States.
David C
DC
Christiani
Department 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.
Sidong
S
Chen
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. Electronic address: miaoxp@mail.hust.edu.cn.
Xiaoping
X
Miao
D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D053673:Glypicans / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C106228:GPC5 protein, human; D053673:Glypicans
Function prediction; GPC5; Lung cancer in never smokers; Single nucleotide polymorphism