TY - JOUR
T1 - Identification of TRPCs genetic variants that modify risk for lung cancer based on the pathway and two-stage study
AU - Zhang, Zili
AU - Wang, Jian
AU - He, Jianxing
AU - Zeng, Xiansheng
AU - Chen, Xindong
AU - Xiong, Mingmei
AU - Zhou, Qipeng
AU - Guo, Meihua
AU - Li, Defu
AU - Lu, Wenju
N1 - Funding Information:
This work was supported by Guangdong Natural Science Foundation Team Grant ( 1035101200300000 ), the National Natural Science Foundation of China ( 81170052 , 81071917 , 81173112 , 81520108001 , and 81220108001 ), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme to W. Lu (2014) and the Key Project of Department of Education of Guangdong Province ( cxzd1142 ), a Guangdong Department of Education Research Grant ( cxzd1025 ), Guangzhou Department of Education Yangcheng Scholarships ( 12A001S ), Guangzhou Department of Education Team Grant for Innovation ( 13C08 ), Guangdong Natural Science Foundation ( 1614050002587 ) and Guangzhou Municipal University Research Projects ( 1201430298 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2016.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Objective: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca2+ concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. Methods: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform. Results: We found consistently significant associations of TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 with increased risk of lung cancer among the three kinds of sources of populations (additive model in combined population: adjusted OR = 1.33, 95% CI = 1.11-1.59 for rs9547991; adjusted OR = 1.21, 95% CI = 1.08-1.35 for rs978156; and adjusted OR = 1.28, 95% CI = 1.10-1.47 for rs11748198). When combining the effects of TRPC7 rs11748198, and TRPC4 rs9547991 and rs978156, subjects carrying "≥1" variant alleles had a 1.29-fold increased risk of lung cancer (95% CI = 1.15-1.46), compared with those carrying "0" variant allele. Lung cancer risk significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend = 7.2 × 10-7). Conclusion: These findings suggested that TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 were candidate susceptibility markers for lung cancer in Chinese population. Our study provides the epidemiological evidence supporting a connection between TRPC members and lung cancer risks.
AB - Objective: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca2+ concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. Methods: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform. Results: We found consistently significant associations of TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 with increased risk of lung cancer among the three kinds of sources of populations (additive model in combined population: adjusted OR = 1.33, 95% CI = 1.11-1.59 for rs9547991; adjusted OR = 1.21, 95% CI = 1.08-1.35 for rs978156; and adjusted OR = 1.28, 95% CI = 1.10-1.47 for rs11748198). When combining the effects of TRPC7 rs11748198, and TRPC4 rs9547991 and rs978156, subjects carrying "≥1" variant alleles had a 1.29-fold increased risk of lung cancer (95% CI = 1.15-1.46), compared with those carrying "0" variant allele. Lung cancer risk significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend = 7.2 × 10-7). Conclusion: These findings suggested that TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 were candidate susceptibility markers for lung cancer in Chinese population. Our study provides the epidemiological evidence supporting a connection between TRPC members and lung cancer risks.
KW - Genetic variants
KW - Lung cancer
KW - ROCCs
KW - SOCCs
KW - TRPCs
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U2 - 10.1016/j.mgene.2016.07.005
DO - 10.1016/j.mgene.2016.07.005
M3 - Article
C2 - 27617218
AN - SCOPUS:84978737087
SN - 2214-5400
VL - 9
SP - 191
EP - 196
JO - Meta Gene
JF - Meta Gene
ER -