X-ray repair cross-complementing 1 polymorphism and prognosis of platinum-based chemotherapy in gastric and colorectal cancer: a meta-analysis

Abstract

Background and aim: The relationships between the X-ray repair cross-complementing 1 (XRCC1) Arg399Gln polymorphism (rs25487, G > A) and responses to platinum-based chemotherapy of gastric and colorectal cancer patients are controversial. Therefore, we performed a meta-analysis to assess the relationships.

Methods: We retrieved the relevant articles from MEDLINE and EMBASE databases. Fourteen studies with 1618 gastric and colorectal cancer patients were included. Primary outcomes included response rate (RR), progression-free survival (PFS), and overall survival (OS). Odds ratio (OR) or hazard ratio with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software version 11.0 and Review Manager (v5.0).

Results: In the dominant model, the A allele of XRCC1 Arg399Gln polymorphism was associated with reduced RR to platinum-based chemotherapy in all gastric and colorectal cancer patients (A/G + A/A vs G/G OR, 0.73; 95% CI, 0.55-0.96) and in Asians (OR, 0.62; 95% CI, 0.44-0.89) but not in Caucasians (OR, 0.92; 95% CI, 0.60-1.42). In addition, stratified analysis for different types of cancers indicated a marginally significant decrease of RR in colorectal cancer patients (OR, 0.68; 95% CI, 0.46-1.00) but not in gastric cancer patients (OR, 0.78; 95% CI, 0.53-1.15). However, we did not observe a significant association between XRCC1 Arg399Gln polymorphism and hazard for PFS and OS for gastric and colorectal cancer patients in all tested models.

Conclusions: XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for platinum-based chemotherapy of gastric and colorectal cancer patients, and more well-designed studies with large samples are needed to confirm our findings.

Keywords: XRCC1; chemotherapy; gastric and colorectal cancer; gene polymorphism; meta-analysis.