Predictive Value of XRCC1 Gene Polymorphisms on Platinum-Based Chemotherapy in Advanced Non–Small Cell Lung Cancer Patients: A Systematic Review and Meta-analysis

Abstract

Purpose: 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.Experimental Design: 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.Conclusion: 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.

No Association of XRCC1 and CLPTM1L Polymorphisms with Non-small Cell Lung Cancer in a Non-Smoking Han Chinese Population

“…XRCC1 protein can bind to platinum-containing DNA duplexes (Zhu and Lippard, 2009) and contributed to repair of platinum-induced DNA damage. Previous studies reported that XRCC1 Arg399Gln polymorphism was associated with the clinical outcome of chemotherapy in lung cancer patients (Horgan et al, 2011;Wu et al, 2012), although our current data didn't show XRCC1 gene (rs2256507 and rs1001581) SNPs to be significantly associated with NSCLC risk in never smokers. These data demonstrated that the effects of XRCC1 SNPs on NSCLC risk and treatment outcome may be dependent on ethnicity of patients.…”

XRCC1 and ADPRT Polymorphisms Associated with Survival in Breast Cancer Cases Treated with Chemotherapy

“…There are increasing evidences that the DNA repair genes polymorphisms induce inter-individual variability in chemotherapy, and the reduced DNA capacity from DNA repair genes contributed to the longer survival after treatment with chemotherapy in various cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, and head and neck squamous cell carcinoma (Ang et al, 2011;Giovannetti et al, 2011;Liu et al, 2012;Wu et al, 2012). Thus, the use of DNA repair gene polymorphisms as predictive or prognostic markers holds clinical promise.…”

“…Although the major prognostic factors for breast cancer is the cancer stage, there are differences in survival among breast cancer patients with similar disease stages. Recently, a number of studies have revealed that polymorphisms in certain genes, especially DNA repair genes, have a role in tumor response to chemotherapy and thus survival variability among individual patients (Ang et al, 2011;Giovannetti et al, 2011;Liu et al, 2012;Wu et al, 2012). Therefore, better understanding of prognostic factors would be helpful for individualizing breast cancer treatment.…”

Prognostic significance of XRCC1, XDP and XRCC3 polymorphisms in non-small cell lung cancer patients with platinum-based chemotherapy

“…Reported associations between the XRCC3 Thr241Met polymorphism and cancer risk are inconsistent, and the variant XRCC3 241Met allele has been both positively and negatively associated with various cancer (Jacobsen et al, 2004;Wang et al, 2003;Misra et al, 2003). Previous study also reported that XRCC3 polymorphisms could influence the survival of NSCLC (Wu et al, 2012;Liao et al, 2012). However, study regarding the influence of combination XRCC1 and XRCC3 gene polymorphisms on survival of NSCLC is lacking.…”