Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.
BACKGROUND
Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.


OBJECTIVE
An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A).


METHODS
Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations.


RESULTS
Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67-0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69-0.91, P = 0.001).


CONCLUSIONS
Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.
Molecular Epidemiology Laboratory, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China; Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Jinhong
J
Zhu
Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Rui-Xi
RX
Hua
Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Jing
J
Jiang
Department of Hematology, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
Li-Qin
LQ
Zhao
Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Xiuwei
X
Sun
Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Jinwei
J
Luan
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Yaoguo
Y
Lang
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Yanqi
Y
Sun
Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
Kun
K
Shang
Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Shiyun
S
Peng
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Jianqun
J
Ma
D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases