Single-nucleotide polymorphisms in DNA bypass polymerase genes and association with breast cancer and breast cancer subtypes among African Americans and Whites

DNA damage recognition and repair is a complex system of genes focused on maintaining genomic stability. Recently, there has been a focus on how breast cancer susceptibility relates to genetic variation in the DNA bypass polymerases pathway. Race-stratified and subtype-specific logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between 22 single-nucleotide polymorphisms (SNPs) in seven bypass polymerase genes and breast cancer risk in the Carolina Breast Cancer Study, a population-based, case–control study (1,972 cases and 1,776 controls). We used SNP-set kernel association test (SKAT) to evaluate the multi-gene, multi-locus (combined) SNP effects within bypass polymerase genes. We found similar ORs for breast cancer with three POLQ SNPs (rs487848 AG/AA vs. GG; OR = 1.31, 95 % CI 1.03–1.68 for Whites and OR = 1.22, 95 % CI 1.00–1.49 for African Americans), (rs532411 CT/TT vs. CC; OR = 1.31, 95 % CI 1.02–1.66 for Whites and OR = 1.22, 95 % CI 1.00–1.48 for African Americans), and (rs3218634 CG/CC vs. GG; OR = 1.29, 95 % CI 1.02–1.65 for Whites). These three SNPs are in high linkage disequilibrium in both races. Tumor subtype analysis showed the same SNPs to be associated with increased risk of Luminal breast cancer. SKAT analysis showed no significant combined SNP effects. These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer.     

The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis

Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR = 0.71, 95 % CI = 0.551–0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312–0.550) and dominant model (OR 0.537, 95 % CI 0.370–0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595–0.861), homozygote codominant (OR 0.537, 95 % CI 0.370–0.781) and dominant model (OR 1.595, 95 % CI 1.207–2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603–0.720) and homozygote codominant models (OR = 0.344, 95 % CI = 0.282–0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no significant associations existed between LEPR rs8179183, rs4655537, and rs3762274 polymorphisms and risk of breast cancer.     

Association of rs2233678 and rs2233679 polymorphisms in the PIN1 gene with cancer risk: a meta-analysis

To data, epidemiological studies have assessed the association between peptidyl-propyl-cis/trans isomerase 1 (PIN1) gene polymorphisms and cancer risk, including breast cancer, hepatocellular carcinoma, lung cancer, esophageal cancer, head and neck squamous cell carcinoma, and laryngeal squamous cell cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs2233678 and rs2233679) of PIN1 gene and cancer risk by conducting a meta-analysis of case–control studies. A total of seven publications were included in this meta-analysis for both rs2233678 and rs2233679. Overall, rs2233678 polymorphism was found to be associated with decreased cancer risk in four genetic models (C-allele vs. G-allele: odd ratio (OR)?=?0.73, 95 % confidence interval (CI): 0.60–0.88; CC vs. GG: OR?=?0.55, 95 % CI: 0.36–0.84; CC+CG vs. GG: OR?=?0.72, 95 % CI 0.58–0.90; CC vs. CG+GG: OR?=?0.58, 95 % CI 0.38–0.89). However, the rs2233679 polymorphism of PIN1 gene did not appear to have an influence on caner susceptibility. In the subgroup analysis by cancer type, we observed that the PIN1 rs2233678 polymorphism was significantly associated with decreased breast cancer risk (C-allele vs. G-allele: OR?=?0.73, 95 % CI: 0.60–0.89; CC+CG vs. GG: OR?=?0.71, 95 % CI 0.57–0.89). Further subgroup analyses showed that the PIN1 rs2233678 polymorphism was associated with decreased cancer risk among Asian people (C-allele vs. G-allele: OR?=?0.63, 95 % CI: 0.51–0.79; CC vs. GG: OR?=?0.44, 95 % CI: 0.25–0.80; CC+CG vs. GG: OR?=?0.63, 95 % CI 0.50–0.79; CC vs. CG+GG: OR?=?0.47, 95 % CI 0.26–0.86). In conclusion, PIN1 rs2233678 polymorphism might be a potential biomarker for cancer risk among Asians, especially for breast cancer. Further large and well-designed studies are needed to confirm this conclusion.     

Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population

Inability to correctly repair DNA damage is known to play a role in the development of breast cancer. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been identified, which modify the DNA repair capacity, which in turn may affect the risk of developing breast cancer. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 62 SNPs in 29 genes in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. Five SNPs were associated with breast cancer. SNPs rs13312840 and rs769416 in the NBS1 gene were associated with a decrease in breast cancer risk (OR TT vs. TC/CC = 0.58; 95% CI, 0.37–0.92; P = 0.019 and OR GG vs. GT/TT = 0.23, 95% CI 0.06–0.85, P = 0.017, respectively). The variant allele of MRE11A rs556477 was also associated with a reduced risk of developing the disease (OR AA vs. AG/GG = 0.76; 95% CI, 0.64–0.91; P = 0.0022). MUS81 rs545500 and PBOV1 rs6927706 SNPs were associated with an increased risk of developing breast cancer (OR GG vs. GC/CC = 1.21, 95% CI, 1.02–1.45; P = 0.031; OR AA vs. AG/GG = 1.53, 95% CI, 1.07–2.18; P = 0.019, respectively). Finally, haplotype-based tests identified significant associations between specific haplotypes in MRE11A and NBS1 genes and breast cancer risk. Further large-scale studies are needed to confirm these results.     

Quantitative assessment of the association between three polymorphisms in FAS and FASL gene and breast cancer risk

FAS and FAS ligand (FASL) play crucial roles in apoptotic signaling, and deregulation of this pathway may facilitate carcinogenesis. Studies on the association between the FAS/FASL polymorphisms (FAS-1377G/A rs2234767, FAS-670A/G rs1800682, and FASL-844C/T rs763110) and breast cancer risk have reported inconsistent results. Therefore, to characterize the relationship between those polymorphisms and breast cancer risk, we undertook a meta-analysis of those studies. Several electronic databases were searched for articles on the FAS/FASL polymorphisms and breast cancer risk. The genotype data were extracted; pooled odds ratios (OR) with 95 % confidence intervals (CIs) were used to estimate the strength of the association. Five studies were eligible for our meta-analysis. Overall, we observed significant associations of the FAS-1377G/A polymorphism with breast cancer susceptibility (AG vs. GG: OR?=?1.15, 95 % CI 1.02–1.30; AA vs. GG: OR?=?1.39, 95 % CI 1.12–1.72; AG/AA vs. GG: OR?=?1.18, 95 % CI, 1.16–1.32; A vs. G: OR?=?1.16, 95 % CI 1.06–1.26), but we did not observe significant association of the Fas-670A/G and FasL-844C/T polymorphisms with breast cancer risk. In the subgroup analysis, we observed that the FAS-1377G/A and FASL-844C/T polymorphisms were associated with breast cancer risk in Chinese but not Whites; we still did not observed association of the FAS-670A/G polymorphism with breast cancer risk. Our meta-analysis revealed that FAS-1377G>A polymorphism was associated with an increased risk of breast cancer. FASL-844C>T polymorphism might be associated with a reduced breast cancer risk in Chinese. However, FAS-670A/G had no any effect on breast carcinogenesis.     

Association of MTHFR C677T polymorphisms and colorectal cancer risk in Asians: evidence of 12,255 subjects

Objectives

To investigate the relationship of the MTHFR polymorphisms (C677T) and the risk of CRC by meta-analysis.

Methods

Relevant literatures concerning the association between the MTHFR C677T polymorphism and the risk of CRC were searched using the electronic database PubMed, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI). Odds ratio (ORs) and 95 % confidence intervals (CIs) were determined to assess the gene–disease association using fixed or random effect models, according to the heterogeneity among included studies.

Results

The study shows that the MTHFR 677 TT homozygous genotype significantly decreases the risk of CRC in Asians (TT vs. CC: OR = 0.82, 95 % CI 0.73–0.92; TT vs. CT: OR = 0.84, 95 % CI 0.75–0.94; TT vs. CC+TT: OR = 0.83, 95 % CI 0.75–0.93).

Conclusion

This meta-analysis indicated that the MTHFR 677 TT homozygous genotype decreased the risk of CRC in Asians, while the MTHFR 677 CT heterozygous genotype did not contribute to CRC susceptibility.     

Murine double minute 2 rs2279744 polymorphism and hepatocellular carcinoma risk in East Asians: a meta-analysis

Murine double minute 2 (MDM2) is a crucial negative regulator of p53 function through several mechanisms. There are many studies performed to assess the association between MDM2 rs2279744 polymorphism and hepatocellular carcinoma risk, but the impact of MDM2 rs2279744 polymorphism on hepatocellular carcinoma in East Asians is unclear owing to the inconsistent findings from previous studies. We conducted a comprehensive meta-analysis of epidemiological studies to shed some light on these contradicting results. We used pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) to assess the association. Overall, seven studies with a total of 4,993 subjects were finally included. The meta-analysis suggested that MDM2 rs2279744 polymorphism was significantly associated with increased risk of hepatocellular carcinoma in East Asians (G versus T: OR?=?1.27, 95 % CI 1.06–1.52, P?=?0.01; GG versus TT: OR?=?1.59, 95 % CI 1.11–2.27, P?=?0.01; GG/GT versus TT: OR?=?1.41, 95 % CI 1.07–1.87, P?=?0.02; GG versus TT/GT: OR?=?1.32, 95 % CI 1.08–1.62, P?=?0.008). Sensitivity analysis by excluding low-quality study still suggested that the association above was still significant. Thus, the findings from the meta-analysis support that MDM2 rs2279744 polymorphism is significantly associated with increased risk of hepatocellular carcinoma in East Asians.     

Quantitative assessment of the association between microRNA-499 rs3746444 A/G polymorphism and cancer risk

Many epidemiological studies have evaluated the association between microRNA-499 rs3746444 A/G polymorphism and cancer risk, but published data are still inconclusive. Therefore, we performed a meta-analysis to evaluate the association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility. The summary odds ratio (OR) with its 95 % confidence interval (CI) was calculated to evaluate the association. Seventeen case–control studies with a total of 7,974 cancer cases and 9,404 controls were finally included into this meta-analysis. Overall, microRNA-499 rs3746444 A/G polymorphism was significantly associated with increased risk in both the domain model (GG/AG versus AA: OR?=?1.17, 95 % CI, 1.03–1.33, P?=?0.02) and the heterozygote comparison model (AG versus AA: OR?=?1.15, 95 % CI, 1.01–1.32, P?=?0.03) when all studies were pooled into the meta-analysis. Subgroup analysis by ethnicity showed that association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility was significant in Asians, but not in Caucasians. In the subgroup analysis by cancer types, no risk of breast, liver, or lung cancers were found significantly associated with microRNA-499 rs3746444 A/G polymorphism in any of the genetic models. In summary, this meta-analysis suggests that microRNA-499 rs3746444 A/G polymorphism is associated with increased susceptibility to cancer in Asians. However, more well-designed studies with large sample size are needed to validate this association among different kinds of cancers.     

XRCC3 5′-UTR and IVS5-14 polymorphisms and breast cancer susceptibility: a meta-analysis

Published data on the association between XRCC3 5′-UTR and IVS5-14 polymorphisms and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between these polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. A total of four studies were involved in the meta-analysis with 6,303 cases and 6,563 controls for XRCC3 5′-UTR polymorphism and with 6,270 cases and 6,682 controls for XRCC3 IVS5-14 polymorphism. For XRCC3 5′-UTR A/G polymorphism, significantly elevated breast cancer risk was associated with variant genotype when all studies were pooled into the meta-analysis (AG vs. AA: OR = 1.11, 95% CI = 1.03–1.19; dominant model: OR = 1.09, 95% CI = 1.01–1.17). For XRCC3 IVS5-14 A/G polymorphism, significantly decreased breast cancer risk was associated with variant genotype (GG vs. AA: OR = 0.86, 95% CI = 0.77–0.96). In conclusion, this meta-analysis suggests that the variant G allele of XRCC3 5′-UTR polymorphism is a low-penetrant risk factor for developing breast cancer, while the variant G allele of XRCC3 IVS5-14 polymorphism has a protective effect on breast cancer development.     

MDM2 SNP309 variation increases cervical cancer risk among Asians

MDM2 T309G polymorphism has been suggested to be a risk factor for a number of cancers. The association of MDM2 T309G genetic variation with cervical cancer risk remains inconclusive. In the present study, we aimed to get a more confidential result by conducting a quantitative meta-analysis. Relevant literature up to October 2013 was searched and screened. Essential information was rigorously extracted for data pooling and analyzing, and then, separate analyses on ethnicity and source of controls were also performed. As a result, four articles including five case–control studies were selected. The overall data failed to show a significant association between MDM2 T309G polymorphism and cervical cancer risk (GG vs TT: odds ratio (OR)?=?1.31; 95 % confidence interval (CI)?=?0.55–3.13; dominant model: OR?=?1.22; 95 % CI?=?0.65–2.31; recessive model: OR?=?1.45; 95 % CI?=?0.79–2.65). However, in the subgroup analysis about ethnicity, increased cancer risk could be shown among Asians (GG vs TT: OR?=?2.15; 95 % CI?=?1.03–4.51; recessive model: OR?=?2.01; 95 % CI?=?1.32–3.06). In conclusion, the results of the present study suggest that homozygous GG alleles of MDM2 T309G polymorphism might be a risk factor for cervical cancer among Asians. Further studies are needed get a more definitive conclusion.     

Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a meta-analysis involving 46,281 subjects

Published data on the association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the GSTM1 present/null polymorphism and breast cancer risk. The pooled ORs were performed for null versus present genotype. A total of 59 studies including 20,993 cases and 25,288 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with null genotype when all studies were pooled into the meta-analysis (OR = 1.10, 95% CI = 1.04–1.16). In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (OR = 1.05, 95% CI = 1.00–1.10) and Asians (OR = 1.21, 95% CI = 1.08–1.35). When stratified by population-based studies or hospital-based studies, statistically significantly elevated risks were found among population-based studies (OR = 1.11, 95% CI = 1.03–1.20). In the subgroup analysis by menopausal status, statistically significantly increased risks were found among postmenopausal women (OR = 1.15, 95% CI = 1.04–1.28). In conclusion, this meta-analysis suggests that the GSTM1 null genotype is a low-penetrant risk factor for developing breast cancer.     

Vitamin D receptor gene ApaI polymorphism and breast cancer susceptibility: a meta-analysis

Vitamin D receptor (VDR) principally mediates the anticancer activities of vitamin D. Many studies investigated the association between VDR gene ApaI polymorphism and breast cancer, but the results were inconclusive. We performed this meta-analysis to evaluate the association between VDR gene ApaI polymorphism and breast cancer. Twelve studies with a total of 8,254 subjects were identified from PubMed and Wanfang databases. The pooled odds ratio (OR) and confidence intervals (95 % CI) were used to assess the association. The meta-analysis indicated that VDR gene ApaI polymorphism was not associated with risk of breast cancer (a vs. A: OR?=?0.97, 95 % CI 0.91–1.04, P?=?0.378; aa vs. AA: OR?=?0.97, 95 % CI 0.85–1.10, P?=?0.618; aa vs. AA + Aa: OR?=?1.00, 95 % CI 0.89–1.12, P?=?0.972; aa + Aa vs. AA: OR?=?0.95, 95 % CI 0.82–1.11, P?=?0.550). Subgroup analysis by ethnicity further showed that VDR gene ApaI polymorphism was not associated with risk of breast cancer in both Asians and Caucasians. These data from the meta-analysis indicate that VDR gene ApaI polymorphism is not associated with breast cancer susceptibility.     

A systemic assessment of the association between tumor necrosis factor alpha 308 G/A polymorphism and risk of cervical cancer

Tumor necrosis factor alpha (TNF-α) is a multifunctional cytokine which plays an important role in the human immune response against various pathogens, and there may be a relationship between TNF-α 308 G/A polymorphism and cervical cancer risk. We performed a meta-analysis to get a systemic assessment of the association between TNF-α 308 G/A polymorphism and cervical cancer risk. Electronic searches of PubMed, Embase, and Web of Science were performed for all publications on the association between TNF-α 308 G/A polymorphism and cervical cancer risk through October 26, 2012. The pooled odds ratios (ORs) with their 95 % confidence interval (95 % CIs) were calculated to assess the association. Fifteen studies with a total of 3,743 cervical cancer cases and 4,096 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with increased risk of cervical cancer under three main genetic comparison models (A vs. G, OR 1.20, 95 % CI 1.02–1.42, P?=?0.03; AA vs. GG, OR 1.31, 95 % CI 1.00–1.72, P?=?0.048; AA vs. GG/GA, OR 1.30, 95 % CI 1.00–1.71, P?=?0.05). Subgroup analysis by ethnicity further showed that there was a significant association between TNF-α 308 G/A polymorphism and increased risk of cervical cancer in Asians (AA vs. GG, OR 1.83, 95 % CI 1.05–3.20, P?=?0.034; AA vs. GG/GA, OR 1.84, 95 % CI 1.05–3.22, P?=?0.032). The meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with increased risk of cervical cancer, and TNF-α 308 G/A mutant allele A is a risk factor of cervical cancer.     

CD243 gene polymorphism significantly associated with breast cancer susceptibility

We aimed to obtain a summary risk estimate for CD243 gene polymorphism associated with breast cancer. A total of nine case–control studies, including 5,073 cancer patients and 7,498 control subjects, were pooled in our fixed effects meta-analysis of the association between CD243 gene polymorphism and risk of breast cancer. All data were analyzed by using Stata software (version 12.0). We found significant risk effects under TT vs. TC?+?CC genetic model [odds ratio (OR)?=?1.09, 95 % confidence interval (CI)?=?1.01–1.18, P?=?0.516], but not in other comparisons. Stratifying the pooled data by ethnicity and source of controls revealed that the association between the T allele and an increased risk of breast cancer was more pronounced among Asians (TT vs. CC: OR?=?1.26, 95 % CI?=?1.02–1.57, P?=?0.720; TT vs. TC?+?CC: OR?=?1.31, 95 % CI?=?1.07–1.61, P?=?0.708) and hospital-based studies (TT vs. CC: OR?=?1.25, 95 % CI?=?1.02–1.53, P?=?0.877; TT vs. TC?+?CC: OR?=?1.27, 95 % CI?=?1.05–1.53, P?=?0.540). No notable heterogeneity was indicated across studies. Our meta-analysis demonstrates that CD243 gene polymorphism may act as a predisposition factor for breast cancer, particularly in Asian populations.     

Racial disparities in red meat and poultry intake and breast cancer risk

Purpose

Research on the role of red meat and poultry consumption in breast carcinogenesis is inconclusive, but the evidence in African-American (AA) women is lacking. The association between consuming meat and breast cancer risk was examined in the Women’s Circle of Health Study involving 803 AA cases, 889 AA controls, 755 Caucasian cases, and 701 Caucasian controls.

Methods

Dietary information was collected using a Food Frequency Questionnaire. Odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models adjusting for potential covariates.

Results

Comparing the fourth versus the first quartiles, among Caucasian women, processed meat (OR = 1.48; 95 % CI 1.07–2.04), unprocessed red meat (OR = 1.40; 95 % CI 1.01–1.94), and poultry intakes (OR = 1.42; 95 % CI 1.01–1.99) increased breast cancer risk. Risk associated with poultry intake was more dominant in premenopausal women (OR = 2.33; 95 % CI 1.44–3.77) and for women with ER? tumors (OR = 2.55; 95 % CI 1.29–5.03) in the Caucasian group. Associations in AA women were mostly null except for a significant increased risk trend with processed meat consumption for ER+ tumors (OR = 1.36; 95 % CI 0.94–1.97, p trend = 0.04).

Conclusions

Overall, associations between breast cancer risk and consumption of red meat and poultry were of different magnitude in AA and Caucasian women, with further differences noted by menopausal and hormone receptor status in Caucasian women. This is the first study to examine racial differences in meat and breast cancer risk and represents some of the first evidence in AA women.     

Association between FAS A670G polymorphism and susceptibility to cervical cancer: evidence from a meta-analysis

Previous studies published to evaluate the association between FAS A670G polymorphism and susceptibility to cervical cancer provided conflicting findings. A meta-analysis of published case–control studies was performed to get a comprehensive evidence for the possible association. We searched in PubMed and Wanfang databases for eligible studies published before February 10, 2013. The odds ratio (OR) with 95 % confidence interval (95 % CI) was used to evaluate the association. Ten studies with a total of 4,904 participants were finally included into the meta-analysis. Overall, there was no obvious association between FAS A670G polymorphism and susceptibility to cervical cancer under all four genetic models (G versus A: OR?=?0.97, 95 % CI 0.84–1.11, P?=?0.64; GG versus AA: OR?=?0.92, 95 % CI 0.69–1.24, P?=?0.60; GG/AG versus AA: OR?=?0.99, 95 % CI 0.77–1.26, P?=?0.92; GG versus AA/AG: OR?=?0.92; 95 % CI 0.68–1.25, P?=?0.59). Subgroup analyses by ethnicity further showed that there was no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians. There was no risk of publication bias. In summary, the meta-analysis suggests that there is no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians.     

The association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility: a meta-analysis based on case–control studies

Published data regarding the association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility showed inconclusive results. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, Elsevier, and Springer for relevant articles published before December 10. 2013. The strength of association between APE1 Asp148Glu polymorphism and breast cancer susceptibility was assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) using the software Stata (version 10.0). A total of 7 case–control studies including 3,460 cases and 3,909 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and breast cancer susceptibility for GG vs TT (OR?=?1.00, 95 % CI?=?0.87–1.14); TG vs TT (OR?=?1.06, 95 % CI?=?0.95–1.18); the dominant model GG?+?TG vs TT (OR?=?1.04, 95 % CI?=?0.94–1.16) and the recessive model GG vs TG?+?TT (OR?=?0.99, 95 % CI?=?0.88–1.11). In subgroup analysis, a significant association was found for TG vs TT in Asian subgroup (OR?=?1.17, 95 % CI?=?1.00?~?1.36) and in population-based subgroup (OR?=?1.18, 95 % CI?=?1.00?~?1.38). This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for breast cancer susceptibility among Asian population.     

Regulator of telomere elongation helicase 1 (RTEL1) rs6010620 polymorphism contribute to increased risk of glioma

Regulator of telomere elongation helicase 1 (RTEL1) is critical for genome stability and tumor avoidance. Many studies have reported the associations of RTEL1 rs6010620 with glioma risk, but individually published results were inconclusive. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. The PubMed, Embase, and Web of Science were systematically searched to identify relevant studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were computed to estimate the strength of the association using a fixed or random effects model. Ten studies were eligible for meta-analysis including data on glioma with 6,490 cases and 9,288 controls. Overall, there was a significant association between RTEL1 rs6010620 polymorphism and glioma risk in all four genetic models (GG vs. AA: OR?=?1.87, 95 % CI?=?1.60–2.18, P _{heterogeneity} ?=?0.552; GA vs. AA: OR?=?1.30, 95 % CI?=?1.16–1.46, P _{heterogeneity} ?=?0.495; dominant model—GG?+?GA vs. AA: OR?=?1.46, 95 % CI?=?1.31–1.63, P _{heterogeneity} ?=?0.528; recessive model—GG vs. GA?+?AA: OR?=?1.36, 95 % CI?=?1.27–1.46, P _{heterogeneity} ?=?0.093). Subgroup analyses by ethnicity showed that RTEL1 rs6010620 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In the stratified analysis by ethnicity and source of controls, significantly increased risk was observed for Asians and Europeans in all genetic models, population-based studies in all genetic models, and hospital-based studies in three genetic models (heterozygote comparison, homozygote comparison, and dominant model). Our meta-analysis suggested that RTEL1 rs6010620 polymorphism is likely to be associated with increased glioma risk, which lends further biological plausibility to these findings.     

Tumor necrosis factor-α 238 G/A polymorphism and gastric cancer risk: a meta-analysis

Though many studies were performed to assess the association between tumor necrosis factor-α (TNF-α) 238 G/A polymorphism and gastric cancer risk, there were no conclusive findings. A meta-analysis of previous published studies was performed to get a comprehensive assessment of the association between TNF-α 238 G/A polymorphisms and gastric cancer. The pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to assess the association. Fifteen studies with a total of 7,795 participants were finally included into this meta-analysis. Overall, there was an obvious association between TNF-α 238 G/A polymorphism and increased risk of gastric cancer (A vs. G: OR?=?1.32, 95 % CI 1.02–1.72, P?=?0.036; GA vs. GG: OR?=?1.32, 95 % CI 1.01–1.72, P?=?0.042; and AA/GA vs. GG: OR?=?1.34, 95 % CI 1.02–1.76, P?=?0.036). Subgroup analysis by ethnicity showed the statistically significant association between TNF-α 238 G/A polymorphism and gastric cancer was limited to Asian populations (A vs. G: OR?=?1.59, 95 % CI 1.29–1.97, P?<?0.001; GA vs. GG: OR?=?1.63, 95 % CI 1.29–2.04, P?<?0.001; and AA/GA vs. GG: OR?=?1.64, 95 %CI 1.31–2.05, P?<?0.001), and there was no obvious association in Caucasians. In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of gastric cancer, especially in Asians.     

Association of MDR1 G2677T polymorphism and leukemia risk: evidence from a meta-analysis

In the light of the relationship between the MDR1 G2677T polymorphism and the risk of leukemia remains inclusive or controversial. For better understanding of the effect of MDR1 G2677T polymorphism on leukemia risk, we performed a meta-analysis. Eligible studies were identified through a search of electronic databases such as PubMed, Excerpta Medica Database (Embase), Cochrane Library, and Chinese Biomedical Literature Database (CBM). The association between the MDR1 G2677T polymorphism and leukemia risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CI). A total of seven publications including eight studies with 1,229 cases and 1,097 controls were included in the meta-analysis. There was no association between MDR1 G2677T polymorphism and leukemia risk in all of five models in overall populations (T vs. G: OR?=?1.00, 95 % CI?=?0.88–1.12, P?=?0.914; TT vs. GG: OR?=?0.97, 95 % CI?=?0.75–1.26, P?=?0.812; TG vs. GG: OR?=?1.00, 95 % CI?=?0.92–1.08, P?=?0.939; TT vs. TG/GG: OR?=?0.98, 95 % CI?=?0.67–1.43, P?=?0.906; TT/TG vs. GG: OR?=?1.00, 95 % CI?=?0.95–1.06, P?=?0.994). However, the significant association was found in others (Table 2) under the homozygote model (TT vs. GG: OR?=?0.68, 95 % CI?=?0.48–0.94, P?=?0.020) and recessive model (TT vs. TG/GG: OR?=?0.63, 95 % CI?=?0.43–0.92, P?=?0.016). In the subgroup analysis, according to the type of leukemia, significant association was found between MDR1 G2677T polymorphism and myeloid leukemia but not lymphoblastic leukemia (TT vs. GG: OR?=?0.66, 95 % CI?=?0.46–0.95, P?=?0.026; TT vs. TG/GG: OR?=?0.56, 95 % CI?=?0.38–0.84, P?=?0.005). The results suggested that there was no association between MDR1 G2677T polymorphism and leukemia risk in overall populations, but significant association was found in others populations (Asians and Africans), and myeloid leukemia indicated that G2677T polymorphism might be a protective factor in the susceptibility of myeloid leukemia and in Asians and Africans.