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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.

SUBMITTER: Li Y

PROVIDER: S-EPMC3440401 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Li Ya Y Liu Fei F Tan Shi-Qiao SQ Wang Yan Y Li Shang-Wei SW

PloS one 20120912 9

<h4>Background</h4>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.<h4>Methods</h4>Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before March 2011.Summ ...[more]

PMID: 22984511

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Project description:AimTo perform a systematic meta-analysis to investigate the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk.MethodsRelevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity.ResultsEleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant association between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg's and Egger's tests did not find any obvious publication bias.ConclusionThe XRCC1 Arg194Trp and Arg399Gln polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement of XRCC1 Arg280His polymorphism in HCC susceptibility.

Project description:IntroductionThe gene XRCC1 (X-ray repair cross-complementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large prospective study of cancer incidence in the USA.MethodsAmong the 21,965 women who were cancer-free in 1992 and gave blood between 1998 and 2001, 502 postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502 controls were matched to cases on age, race/ethnicity, and date of blood collection. Genotyping on DNA extracted from buffy coat was performed with Taqman. Conditional logistic regression was used to examine the association between each polymorphism and breast cancer risk controlling for breast cancer risk factors. We also examined whether factors associated with DNA damage, such as smoking and antioxidant intake, modified the association between XRCC1 polymorphisms and breast cancer.ResultsWe observed a significant inverse association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194 non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95). The inverse association between breast cancer and Trp194 carriers compared with non-carriers was slightly stronger among smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43 to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was observed only among women who reported ever smoking cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non-smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the association between XRCC1 polymorphisms and breast cancer risk.ConclusionOur results support the hypothesis that genetic variation in XRCC1, particularly in Arg194Trp, may influence postmenopausal breast cancer risk. In our study, genetic variation in XRCC1 Arg399Gln was associated with breast cancer risk only among women with a history of smoking cigarettes.

Project description:BackgroundPrevious studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk.MethodsThe PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals.ResultsNo significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models.ConclusionThe meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.

Project description:OBJECTIVES:Glioma is the most common central nervous system tumor. This systematic review and meta-analysis is aimed to systematically assess the association of XRCC1 polymorphisms with the risk of glioma. METHODS:Such databases as EMbase, PubMed, The Cochrane Library, the China National Knowledge Infrastructure (CNKI) platforms, VIP and WanFang were searched up to April 2015 to collect case-control studies of association between XRCC1 polymorphisms and glioma. Data were extracted and meta-analysis was conducted by using Stata 12.0 softwares. RESULTS:A total of 22 studies were included in the meta-analysis, including 18503 glioma patients and 24367 controls. The overall data indicated that XRCC1 Arg194Trp (C>T) polymorphism significantly increased glioma risk (allele C versus T: OR=0.72, 95% CI=0.55-0.93, CC versus TT: OR=0.55, 95% CI=0.46-0.67; CC versus CT+TT: OR=0.64, 95% CI=0.45-0.91 and CC+CT vs. TT: OR=0.61, 95% CI=0.51-0.74), especially in Asia ethnicity. XRCC1 Arg280His (G>A) polymorphism has no association with glioma (allele G versus A: OR=1.01, 95% CI=0.83-1.22; GG versus AA: OR=1.07, 95% CI=0.66-1.75; GA versus AA: OR=1.01, 95% CI=0.77-1.32; GG versus GA+AA: OR=1.01, 95% CI=0.84-1.22 and GG+GT versus AA: OR=1.06, 95% CI=0.67-1.69). XRCC1 Arg399Gln (G>A) polymorphism will significantly increase glioma risk in Asian (allele G versus A: OR=0.78, 95% CI= 0.72-0.84; GG versus AA: OR=0.56, 95% CI=0.47-0.66; GA versus AA OR=0.71, 95% CI=0.59-0.84; GG versus GA+AA: OR=0.76, 95% CI=0.68-0.84 and GG+GA vs. AA: OR=0.62, 95% CI=0.53-0.73) but not Caucasian ethnicity. XRCC1 Pro161Leu (C>T), Leu387Leu (G>A), Pro602Thr (C>A), Ser593Arg (C>G) and Glu491Lys (G>A) polymorphisms increased glioma risk in different degrees. CONCLUSION:This meta-analysis suggested that XRCC1 Arg194Trp and XRCC1 Arg399Gln (G>A) polymorphisms led to susceptibility to glioma in Asian but not Caucasian population. XRCC1 Glu491Lys (G>A), Pro161Leu (C>T), Leu387Leu (G>A), Pro602Thr (C>A), Thr304Ala (A>G) and Ser593Arg (C>G) polymorphisms will increase glioma risk. However, XRCC1 Arg280His (G>A) is irrelevant to the increased or decreased glioma risk.

Dataset Information

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

Publications

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

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