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Meta-analysis of XRCC1 polymorphism and risk of female reproductive system cancer.

ABSTRACT: Numerous epidemiological studies have evaluated the association between polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1) protein and the risk of female reproductive system cancer, but results are inconclusive. To gain a comprehensive picture of available evidence, we searched for relevant studies in the PubMed, EMBASE, Scopus, and Chinese National Knowledge Infrastructure databases up to December 17, 2016. A total of 26 case-control studies were picked out. The pooled odds ratio (OR) with its 95% confidence interval (CI) was calculated to estimate the association. Based on data of all study participants, we did not find a positive association of rs25487 or rs1799782 polymorphism with risk of female reproductive cancer risk. Subgroup analysis, however, identified two alleles as being associated with an increased risk of female reproductive system cancer in Asians: the A allele of rs25487 (heterozygous genetic model, OR 1.16, 95%CI 1.00-1.36), and the T allele of rs1799782 (homozygous model, OR 2.30, 95%CI 1.39-3.82; dominant model, OR 1.28, 95%CI 1.10-1.50; recessive model, OR 2.11, 95%CI 1.33-3.34). Moreover, the AA genotype at rs25489 was determined to be a risk factor for cervical cancer etiology (homozygous model, OR 2.91, 95%CI, 1.17-7.26; recessive model, OR 3.16, 95%CI 1.91-5.24). This meta-analysis suggests that no association between rs25487 or rs1799782 gene polymorphism and risk of female reproductive cancer risk was found. These results should be validated in larger studies.

SUBMITTER: Yang NN

PROVIDER: S-EPMC5438663 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Meta-analysis of XRCC1 polymorphism and risk of female reproductive system cancer.

Yang Na-Na NN Huang Ying-Fan YF Sun Jian J Chen Ying Y Tang Zhong-Min ZM Jiang Jin-Fang JF

Oncotarget 20170401 17

Numerous epidemiological studies have evaluated the association between polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1) protein and the risk of female reproductive system cancer, but results are inconclusive. To gain a comprehensive picture of available evidence, we searched for relevant studies in the PubMed, EMBASE, Scopus, and Chinese National Knowledge Infrastructure databases up to December 17, 2016. A total of 26 case-control studies were picked out. The pooled ...[more]

PMID: 28415705

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Project description:Background and objectiveThe X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study.MethodsPubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status.ResultsA total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively).ConclusionsThis meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.

Project description:BackgroundGynecological malignant tumor is a serious threat to women's health, cervical cancer, endometrial cancer and ovarian cancer are the most common. The eponymous protein encoded by the XRCC1 (X-ray repair cross complementation 1) gene is an important functional protein in the process of single-stranded DNA damage. Non-synonymous mutations of XRCC1 gene cause amino acid sequence changes that affect protein function and DNA repair ability, and may affect the interaction with other DNA repair proteins, leading to increased risk of tumor development. Many studies have assessed the association between XRCC1 gene polymorphism and the risk of cancer in the female reproductive system, but the results have been inconclusive. In this study, the relationship between XRCC1 Arg399Gln, Arg194Trp, Arg280His single nucleotide polymorphisms and susceptibility to gynecological malignancies was further explored by meta-analysis.MethodsEnglish database: Pubmed, Medline, Excerpta Medica Database, Cochrance, etc; Chinese database: China national knowledge infrastructure, Wanfang Database, etc. STATA14 was used for statistical analysis, such as odd ratio (OR) value, subgroup analysis, heterogeneity test, sensitivity analysis, and publication bias.ResultsIn gynecologic cancers, the allele frequency difference of Arg399Gln case control group was statistically significant (GvsA: P = .007). There was no significant difference in allele frequency in the Arg194Trp and Arg280His case control groups (P = .065, 0.198). In different gene models, Arg399Gln was significantly correlated with gynecologic cancers susceptibility (GGvs AA: OR 0.91; 95% confidence interval [CI], 0.85 0.98); Arg194Trp was significantly correlated with gynecologic cancers susceptibility (CCvs TT: OR 0.94; 95% CI 0.88,1.00; CCvs CT: OR 0.97; 95% CI 0.90, 1.05); Arg280His was significantly correlated with gynecologic cancers susceptibility (GGvs AA: OR 0.98; 95% CI 0.94, 1.02; GGvs GA: OR 1.00;95% CI 0.97, 1.04). In the subgroup analysis, Arg399Gln and Arg194Trp were significantly correlated with gynecologic cancers susceptibility in the Asian race (P = .000, 0.049). In the analysis of different cancer subgroups, Arg399Gln and cervical cancer susceptibility were statistically significant (P = .039). Arg194Trp and endometrial cancer susceptibility were statistically significant (P = .033, 0.001).ConclusionsXRCC1 Arg399Gln, Arg194Trp, Arg280His single nucleotide polymorphisms were associated with gynecologic cancer susceptibility. Arg399Gln genotype was statistically significant in relation to cervical cancer susceptibility. Arg194Trp genotype was statistically significant in relation to endometrial cancer susceptibility.

Dataset Information

Meta-analysis of XRCC1 polymorphism and risk of female reproductive system cancer.

Publications

Meta-analysis of XRCC1 polymorphism and risk of female reproductive system cancer.

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