X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and cervical cancer risk: a huge systematic review and meta-analysis

Abstract

Background: Previous studies investigating the association between X-ray repair cross-complementation group 1(XRCC1) polymorphisms and cervical cancer (CC) risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms and risk of CC.

Methods: Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before March 2011.Summary odds ratios (ORs) and 95% confidence intervals (CIs) for XRCC1 polymorphisms and CC were calculated in a fixed-effects model or a random-effects model when appropriate.

Results: Ultimately, 9, 5 and 2 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp and Arg280His, respectively. Our analysis suggested that the variant genotypes of Arg194Trp were associated with a significantly increased CC risk (Trp/Trp vs Arg/Arg, OR = 2.21, 95% CI = 1.60-3.06; Arg/Trp vs Arg/Arg, OR = 1.23, 95% CI = 1.02-1.49; dominant model, OR = 1.36, 95% CI = 1.14-1.63; recessive model, OR = 2.06, 95% CI = 1.51-2.82). For Arg280His polymorphism, no obvious associations were found for all genetic models. For Arg399Gln polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity/country, a significantly increased risk was observed among Asian, especially among Chinese. To get more precise evidences, adjusted ORs (95%CI) by potential confounders (such as age, ethnicity or smoking, etc) were also calculated for XRCC1 Arg399Gln and Arg194Trp, however, the estimated pooled adjusted OR still did not change at all.

Conclusion: This meta-analysis suggests that Arg194Trp polymorphism may be associated with CC risk, Arg399Gln polymorphism might be a low-penetrent risk factor for CC only in Asians, and there may be no association between Arg280His polymorphism and CC risk.

Figure 1. Literature search and study selection procedures used for a meta-analysis of x-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and cervical cancer.

Figure 2. Forest plots of ORs with 95% CI for XRCC1 polymorphisms(Arg194Trp, Arg399Gln) and risk for cervical cancer.

The center of each square represents the OR, the area of the square is the number of sample and thus the weight used in the meta-analysis, and the horizontal line indicates the 95%CI. (A) Arg194Trp, Trp/Trp+Trp/Arg vs. Arg/Arg. (B) Arg399Gln, Gln/Gln+Gln/Arg vs. Arg/Arg.

Figure 3. Influence analysis of the summary odds ratio coefficients on the association between x-ray repair cross-complementing group 1 gene (XRCC1) Arg399Gln GG-plus-GA genotypes with cervical cancer risk.

Results were computed by omitting each study (left column) in turn. Bars, 95% confidence interval.

Figure 4. Results from cumulative meta-analysis of associations between x-ray repair cross-complementing group 1 gene (XRCC1) Arg399Gln GG-plus-GA genotypes (G carrier group), as compared with the AA genotype, and cervical cancer risk.

The circles and horizontal lines show the accumulation of estimates as results from each study were added, rather than the estimate for each individual study. Studies sorted by publication time; Bars, 95% confidence interval.

Figure 5. For XRCC1 Arg399Gln polymorphism, Begg’s funnel plot for publication bias test.

(Gln/Gln vs. Arg/Arg). Each point represents a separate study for the indicated association. LogOR, natural logarithm of OR. Horizontal line, mean effect size.