XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: a meta-analysis.
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ABSTRACT:
SUBMITTER: Yan Y
PROVIDER: S-EPMC3967070 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065-1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099-1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141-1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy-Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.
| S-EPMC4602594 | biostudies-literature
Project description:Polymorphisms in DNA repair genes may alter DNA repair capacity and, consequently, lead to genetic instability and carcinogenesis. Several studies have investigated the association of the Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementation group D (XPD) gene with the risk of non-Hodgkin's lymphoma (NHL), but the conclusions have been inconsistent. Therefore, we performed this meta-analysis to more precisely estimate these relationships. A systematic literature search was performed using the PubMed, Embase, and Chinese Biomedical (CBM) databases. Ultimately, 6 studies of Asp312Asn, comprising 3,095 cases and 3,306 controls, and 7 studies of Lys751Gln, consisting of 3,249 cases and 3,676 controls, were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of each association. Overall, no association was observed between the Asp312Asn polymorphism and NHL risk (homozygous: OR?=?1.11, 95% CI?=?0.94-1.32; heterozygous: OR?=?1.00, 95% CI?=?0.89-1.11; recessive: OR?=?1.12, 95% CI?=?0.95-1.31; dominant: OR?=?1.02, 95% CI?=?0.92-1.13; and allele comparison: OR?=?1.04, 95% CI?=?0.96-1.12) or between the Lys751Gln polymorphism and NHL risk (homozygous: OR?=?0.97, 95% CI?=?0.83-1.15; heterozygous: OR?=?0.96, 95% CI?=?0.86-1.06; recessive: OR?=?1.00, 95% CI?=?0.86-1.16; dominant: OR?=?0.96, 95% CI?=?0.87-1.06; and allele comparison: OR?=?0.98, 95% CI?=?0.91-1.05). Furthermore, subgroup analyses did not reveal any association between these polymorphisms and ethnicity, the source of the controls, or the NHL subtype. These results indicated that neither the Asp312Asn nor Lys751Gln XPD polymorphism was related to NHL risk. Large and well-designed prospective studies are required to confirm this finding.
| S-EPMC4593373 | biostudies-literature
Project description:We performed a comprehensive meta-analysis to determine the association between XPD/ERCC2 Lys751Gln polymorphism and melanoma susceptibility. Based on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between XPD/ERCC2 Lys751Gln polymorphism and melanoma risk. A total of 5,961 cases and 8,669 controls in studies were included in this meta-analysis. All studies were conducted in Caucasian populations. Allele model (Lys vs. Gln: P = 0.53; OR = 0.98, 95% CI = 0.91-1.05), and homozygous model (Lys/ Lys vs. Gln/Gln: P = 0.32; OR = 0.93, 95% CI = 0.81 to 1.07) did not show increased risk of developing melanoma. Similarly, dominant model (Lys/ Lys+Lys/Gln vs. Gln/Gln: P = 0.18; OR = 0.93, 95% CI = 0.83 to 1.03) and recessive model (Lys/ Lys vs. Lys/Gln+Gln/Gln: P = 0.73; OR = 0.98, 95% CI = 0.88 to 1.09) failed to show increased risk of developing melanoma. Our pooled data suggest that there was no evidence for a major role of XPD/ERCC2 Lys751Gln polymorphism in the pathogenesis of melanoma among Caucasian populations.
| S-EPMC4613026 | biostudies-literature
Project description:Objectives: The aim of the present study was to define the potential relationship between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms and the risk of leukemia. Methods: A comprehensive search of Pubmed, Web of Science, EBSCO, the Cochrane Library and China National Knowledge Infrastructure was conducted to identify original articles published before March 2017 concerning the association between XPD Lys751Gln polymorphisms and leukemia risk. A literature quality assessment was performed using the Newcastle-Ottawa Scale. Heterogeneity across studies was assessed using I2 statistics. Random- or fixed-effects models were used to calculate pooled odds ratios (ORs) in the presence or absence of heterogeneity, respectively. Sensitivity analysis was used to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. All data analyses were performed using Stata 14.0 and Revman 5.3. Results: Fourteen studies with a total of 7525 participants (2,757 patients; 4,768 controls) were included in this meta-analysis. We found that XPD Lys751Gln polymorphisms significantly increased the risk of developing leukemia in both dominant OR = 1.21, 95%CI [1.10-1.35], P ? 0.001) and heterozygote (OR = 1.22, 95%CI [1.09-1.36], P ? 0.001) model. An allele model showed a borderline significant increase in leukemia risk (OR = 1.13, 95%CI [1.00-1.27], P = 0.05). A subgroup analysis revealed a consistent association between XPD Lys751Gln polymorphisms and leukemia risk for some genetic models in Caucasian populations, adult or chronic groups, and in almost all models of childhood or acute groups. Conclusion: Our results indicate that XPD Lys751Gln polymorphism increases the risk of leukemia, especially in childhood and acute cases.
| S-EPMC6073102 | biostudies-literature
Project description:BACKGROUND: Whether the single nucleotide polymorphism (SNP) Lys751Gln of xeroderma pigmentosum group D(XPD) gene increases susceptibility to head and neck cancer (HNC) is controversial and undetermined. Therefore, we conducted this meta-analysis to systematically assess the possible association between them. METHODS: The OVID, Medline, Embase, Pubmed, Web of Science databases were searched to identify the eligible studies. The odds ratio (OR) with 95% confidence interval (95% CI) were used to assess the strength of association. RESULTS: A total of 11,443 subjects from eighteen studies were subjected to meta-analysis. Overall, XPD Lys751Gln polymorphism had no association with increased HNC risk under all five genetic models (P > 0.05). In the subgroup analysis by ethnicity and source of controls, still no significant association was found under five genetic models (P > 0.05). In the subgroup analysis by cancer type, XPD Lys751Gln polymorphism had statistically significant association with elevated laryngeal cancer (LC) and nasopharyngeal cancer (NPC) risk under heterozygous comparison and dominant model (P<0.05) and borderline significantly increased risk was found under allele contrast for LC and NPC. Carriers of Lys allele and Lys/Lys genotype may be associated with elevated LC and NPC risk. CONCLUSIONS: There is overall lack of association between XPD Lys751Gln polymorphism and HNC risk under all five genetic models and still no significant association was found in the subgroup analysis by ethnicity and source of controls. However, XPD Lys751Gln polymorphism was significantly associated with susceptibility to LC and NPC and the Lys allele and Lys/Lys genotype of XPD Lys751Gln polymorphism may be a risk factor for LC and NPC. However, relatively modest sample sizes were included in this meta-analysis and studies with large sample sizes and representative population are warranted to further clarify this finding. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5628716106316015.
| S-EPMC3916081 | biostudies-literature
Project description:BACKGROUND:Tumor suppressor gene (TP53) is considered as the most frequently mutated gene in almost all forms of human cancer. Moreover, genetic variations in the XPD gene affect the DNA repair capacity increasing cancer susceptibility. Polymorphisms within these genes can play a major role in determining individual lung cancer susceptibility. However, several studies have investigated this possibility; but reported conflicting results. Therefore, the objective of this study was to investigate the role of TP53 Arg72Pro and XPD Lys751Gln gene polymorphisms on lung cancer susceptibility in the Bangladeshi population. MATERIALS AND METHODS:Study subjects comprised of 180 lung cancer patients and 200 healthy volunteers. Genetic polymorphism of TP53 was determined by multiplex PCR-based method, while XPD genotypes were analyzed using Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP) method. Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI). RESULTS:From the results, no significant association between TP53 Arg72Pro polymorphism and lung cancer risk was observed. Whereas, patients with homozygous mutant variants (Gln/Gln) of XPD at codon 751 were found significantly associated with lung cancer risk when compared to the control (OR=3.58; 95% CI=1.58-8.09; p=0.002). Lung cancer risk was found significantly higher with Gln/Gln variants of XPD among smokers (OR=4.03; 95% CI=1.11-14.63; p=0.026). Significant increased risk of lung cancer was found with Arg/Pro genotypes of TP53, Lys/Gln and Gln/Gln variants of XPD in individuals with family history of cancer (OR=3.44; 95% CI=1.36-8.72; p=0.011; OR=3.17; 95% CI=1.20-8.39; p=0.024; OR=16.35; 95% CI=0.92-289.5; p=0.007, respectively). CONCLUSION:The findings indicated that homozygous mutant variants (Gln/Gln) of XPD were associated with increased lung cancer risk, whereas TP53 Arg72Pro polymorphism was not associated with risk of lung cancer among Bangladeshi patients..
| S-EPMC7573406 | biostudies-literature
Project description:BACKGROUND: To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis. METHODS: We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk. RESULTS: Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR?=?0.95, 95%CI?=?0.80-1.13, P?=?0.550, P(heterogeneity)?=?0.126; Asp/Asn vs. Asp/Asp: OR?=?1.11, 95%CI?=?0.99-1.24, P?=?0.065, P(heterogeneity)?=?0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR?=?1.07, 95%CI?=?0.97-1.19, P?=?0.189, P(heterogeneity)?=?0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR?=?0.87, 95%CI?=?0.68-1.10, P?=?0.243, P(heterogeneity)?=?0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models. CONCLUSIONS: This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.
| S-EPMC3335063 | biostudies-literature
Project description:OBJECTIVE: This meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract. METHODS: Medline (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically "genetic polymorphisms" or "SNPs" or "variation" or "single nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: Six independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated. CONCLUSIONS: The association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract.
| S-EPMC4384174 | biostudies-literature
Project description:AIM:Our aim was to investigate the relationship between transcription factor 7-like 2 (TCF7L2) polymorphisms and breast cancer susceptibility. METHODS:PubMed, Embase and CNKI databases were used to search the related studies investigating the correlation between TCF7L2 polymorphisms and breast cancer susceptibility. Pooled ORs and 95% CIs, based on five genetic models, were applied to estimate the association betweenTCF7L2 polymorphisms and breast cancer. A fixed-effect model or a random-effect model was applied according to the between-study heterogeneity. RESULTS:We analyzed six single nucleotide polymorphisms (SNPs) in TCF7L2 gene, namely rs12255372, rs7903146, rs7900150, rs3750805, rs1225404 and rs7003146. The increased risk of breast cancer was associated with TCF7L2 polymorphisms (22 vs. 11: OR=1.16, 95% CI=1.02-1.32; 22+12 vs. 11: OR=1.06, 95% CI=1.02-1.10; 22 vs. 11+12: OR=1.15, 95% CI=1.04-1.27; 2 vs. 1: OR=1.07, 95% CI=1.02-1.13; 12 vs. 11: OR=1.05, 95% CI=1.01-1.09). Among the locus, rs7903146 polymorphism was significantly associated with the risk for breast cancer under five genetic models (TT vs. CC: OR=1.29, 95% CI=1.08-1.53; TT+CT vs. CC: OR=1.09, 95% CI=1.01-1.18; TT vs. CC+CT: OR=1.24, 95% CI=1.05-1.48; T vs. C: OR=1.11, 95% CI=1.04-1.19; CT vs. CC: OR=1.08, 95% CI=1.00-1.17). Additionally, rs7900150 also showed effects on the susceptibility of breast cancer (TT vs. AA: OR=1.22, 95% CI=1.07-1.39; TT+AT vs. AA: OR=1.06, 95% CI=1.00-1.14; TT vs. AA+AT: OR=1.21, 95% CI=1.07-1.37; T vs. A: OR=1.09, 95% CI=1.02-1.15; AT vs. AA: OR=1.04, 95% CI=1.01-1.33). Meanwhile, we found that rs3750805 polymorphism could increased the risk for breast cancer (TT+AT vs. AA: OR=1.12, 95% CI=1.01-1.24). CONCLUSION:Our meta-analysis demonstrates that TCF7L2 polymorphisms may increase the risk for breast cancer.
| S-EPMC4537972 | biostudies-literature
Project description:PurposeAPOLIPOPROTEIN E (APOE, MIM: 107741) has three functionally distinct isoforms of the protein (E2, E3, and E4), encoded by corresponding alleles ε2, ε3, and ε4, which have been well described. Findings from previous studies investigating association between APOE polymorphisms and breast cancer risk have been inconsistent. The present meta-analysis was conducted in order to investigate association of APOE polymorphisms with risk of breast cancer.Materials and methodsSeveral electronic databases were used for identification of studies containing information on APOE polymorphisms and breast cancer risk published up to January 2012. We identified 10 eligible studies, including 3,835 subjects (2008 patients, and 1,827 healthy controls), that reported on polymorphisms of APOE and risk of breast cancer. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using a fixed and random-effects models.ResultsAmong studies reported from Asia, an association of the ε4 allele with increased risk of breast cancer, in comparison with the ε3 allele, was observed (OR, 1.56; 95% CI, 1.19 to 2.04; p=0.001). It should be noted that allele ε2 showed no association with breast cancer risk. Among Caucasians, neither the ε4 (OR, 0.99; 95% CI, 0.83 to 1.17; p=0.917) nor the ε2 (OR, 0.92; 95% CI, 0.72 to 1.17; p=0.514) allele showed an association with susceptibility to breast cancer, when compared with the ε3 allele. Carriers of the ε4 allele (E4E4, E4E3, and E4E2 genotypes), in comparison with the E3E3 genotype, showed an association with elevated risk of breast cancer only among Asians (OR, 1.75; 95% CI, 1.23 to 2.47; p=0.002). No publication bias was detected.ConclusionThis meta-analysis suggest that the APOEε4 allele is a low-penetrant risk factor for development of breast cancer.
| S-EPMC3394861 | biostudies-literature