Predictive value of XRCC1 gene polymorphisms on platinum-based chemotherapy in advanced non-small cell lung cancer patients: a systematic review and meta-analysis.
OBJECTIVE
Published data have shown conflicting results about the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms (Arg399Gln and Arg194Trp) and clinical outcome of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis is needed to provide a systematic review of the published findings.


METHODS
We conducted a systematic review and meta-analysis to evaluate the predictive value of XRCC1 gene polymorphisms on clinical outcome up to October 1, 2010. The quality of each study was scored on the basis of predefined criteria.


RESULTS
A total of 13 eligible follow-up studies met all the inclusion criteria. The XRCC1194Trp allele was found to be significantly associated with a favorable response rate relative to 194Arg [Trp vs. Arg: OR, 1.88; 95% confidence interval (CI), 1.48-2.38]. XRCC1399Gln was less favorably associated with both response rate (Gln vs. Arg: OR, 0.67; 95% CI, 0.52-0.87) and overall survival (Gln vs. Arg: HR, 1.30; 95% CI, 1.04-1.63) than 399Arg in analyses using all available studies; but these associations became insignificant when only high-quality studies were used.


CONCLUSIONS
These findings suggest a predictive role for XRCC1 gene polymorphisms in clinical outcome. However, the role of 399Gln could be considered controversial because its impact on clinical outcome was insignificant in high-quality studies. These findings show the importance of establishing suitable criteria, including genetic epidemiologic, phenotypic, and clinical criteria, to improve quality control of study design and methods in pharmacogenomic studies related to XRCC1 gene polymorphism.
National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Changhai Hospital of Shanghai, Shanghai, China.
Junjie
J
Wu
Jie
J
Liu
Yuhao
Y
Zhou
Jun
J
Ying
Houdong
H
Zou
Shicheng
S
Guo
Lei
L
Wang
Naiqing
N
Zhao
Jianjun
J
Hu
Daru
D
Lu
Li
L
Jin
Qiang
Q
Li
Jiu-Cun
JC
Wang
D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D010984:Platinum / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011379:Prognosis; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D010984:Platinum