Quantitative assessment of the association between CYP1A1 A4889G polymorphism and endometrial cancer risk

Cytochrome P450 1A1 (CYP1A1) A4889G polymorphism was supposed to be associated with endometrial cancer risk, but previous studies reported conflicting results. We therefore performed a meta-analysis of all relevant studies to get a comprehensive assessment of the association between CYP1A1 A4889G polymorphism and endometrial cancer risk. The pooled odds ratios (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated to assess the association. Finally, ten studies with a total of 1,682 endometrial cancer cases and 2,510 controls were finally included into the meta-analysis. Meta-analysis of the total ten studies showed that CYP1A1 A4889G polymorphism was not associated with endometrial cancer risk (OR_{G versus A}?=?1.14, 95 % CI 0.83–1.57, P _OR?=?0.417; OR_{GG versus AA}?=?1.23, 95 % CI 0.70–2.18, P _OR?=?0.470; OR_{GG versus AA/AG}?=?1.03, 95 % CI 0.59–1.81, P _OR?=?0.919; OR_{GG/AG versus AA}?=?1.22, 95 % CI 0.82–1.81, P _OR?=?0.336). Subgroup analyses by ethnicity further showed that there was also no obvious association between CYP1A1 A4889G polymorphism and endometrial cancer risk in both Caucasians and Asians. Sensitivity analysis by excluding single study in turns showed that the pooled estimations were not stable. Therefore, evidence for currently available data suggests that CYP1A1 A4889G polymorphism is not associated with endometrial cancer risk. However, more studies with large number of participants are needed to further assess the association precisely.     

TaqI polymorphism of VDR gene contributes to breast cancer risk

Previous studies on the association of Vitamin D receptor (VDR) TaqI gene polymorphism with breast carcinogenesis have yielded inconsistent and inconclusive findings. The current meta-analysis was performed to provide a more precise assessment on the role of VDR TaqI polymorphism in breast cancer risk. 20 eligible case–control studies involving 9,055 cases and 10,516 controls were identified after a comprehensive literature search of the PubMed, Embase, Web of Science, and Wanfang databases. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated. Stratified analyses by ethnicity and study quality were conducted for further estimation. All statistical analyses were conducted by use of STATA (STATA Corporation, College Station, TX, Version 11.0). The overall ORs showed that the variant t allele and tt genotype were related to an increased risk of breast cancer (OR_{t vs. T}?=?1.05, 95 % CI 1.01–1.10, P _OR?=?0.025; OR_{tt vs. TT}?=?1.12, 95 % CI 1.03–1.23, P _OR?=?0.011; OR_{tt vs. Tt + TT}?=?1.10, 95 % CI 1.01–1.20, P _OR?=?0.023). Stratified analyses of studies in Caucasians and with high-quality further confirmed the results. However, no significant relationship was observed among Asians. This meta-analysis suggests that the VDR TaqI polymorphism confers risk effect on the breast cancer development, particularly in Caucasians.     

The polymorphism of methylenetetrahydrofolate reductase C677T but not A1298C contributes to gastric cancer

Increasing epidemiological studies have revealed the important role of methylenetetrahydrofolate reductase (MTHFR) in carcinogenesis. The association of MTHFR A1298C and MTHFR C677T polymorphisms with the risk for gastric cancer remains obscure due to inconsistent findings in independent studies among diverse ethnicities. A meta-analysis based on all available publications on this genetic association was performed. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were calculated to estimate the effect of MTHFR variants on gastric carcinogenesis. Totally, 25 eligible case–control studies were included into the meta-analysis according to the inclusion criteria. The MTHFR C677T polymorphism was demonstrated to significantly increase the susceptibility to gastric cancer (OR_{T vs. C}?=?1.21, 95 % CI 1.10–1.34; OR_{TT vs. CC}?=?1.47, 95 % CI 1.22–1.76; OR_{TC vs. CC}?=?1.20, 95 % CI 1.03–1.40; OR_{TT + TC vs. CC}?=?1.27, 95 % CI 1.10–1.47; OR_{TT vs. CC + TC}?=?1.29, 95 % CI 1.15–1.46), whereas no significant correlation was observed when assessing the MTHFR A1298C polymorphism (OR_{C vs. A}?=?1.00, 95 % CI 0.90–1.10; OR_{CC vs. AA}?=?0.99, 95 % CI 0.75–1.31; OR_{CA vs. AA}?=?1.01, 95 % CI 0.89–1.14; OR_{CC + CA vs. AA}?=?1.00, 95 % CI 0.89–1.13; OR_{CC vs. AA + CA}?=?0.97, 95 % CI 0.74–1.27). Subgroup analyses by ethnicity and source of controls further confirmed the findings in overall analysis. The meta-analysis suggests that the polymorphism of MTHFR C677T but not MTHFR A1298C confers a risk effect on the development of gastric cancer among Asians and Caucasians, which provides a new insight into the gastric cancer pathogenesis.     

Significant association between CYP1A1 T3801C polymorphism and cervical neoplasia risk: a systematic review and meta-analysis

Recently, many studies have been published to evaluate the correlation between the cytochrome P450 1A1 (CYP1A1) T3801C polymorphism and cervical neoplasia risk. However, the results remain inconclusive. To clarify this possible association, we conducted a systematic review and meta-analysis of published studies. Data were collected from the following electronic databases: PubMed, Embase, Ovid, ISI Web of Knowledge, Google Scholar, and Chinese Biomedical Database databases. The pooled odds ratio (OR) and its 95 % confidence interval (95 % CI) were used to assess the strength of this association. The pooled ORs were performed for the allele model (C vs. T), the homozygote model (CC vs. TT), the dominant model (CC/CT vs. TT), and the recessive model (CC vs. TT/CT), respectively. Finally, a total of 12 independent studies including a total of 3,724 subjects (1,912 cases/1,812 controls) were eligible for meta-analysis. Overall, there was a significant association between the CYP1A1 T3801C polymorphism and cervical neoplasia susceptibility (C vs. T, OR 1.32, 95 % CI 1.04–1.68, P?=?0.02; CC vs. TT, OR 1.99, 95 % CI 1.19–3.35, P?=?0.01; CC/CT vs. TT, OR 1.36, 95 % CI 1.02–1.81, P?=?0.02; CC vs. TT/CT, OR 1.57, 95 % CI 1.23–2.02, P?<?0.01). Meta-analysis of the ten studies on cervical cancer suggested a significant association between the CYP1A1 T3801C polymorphism and cervical cancer risk (C vs. T, OR 1.38, 95 % CI 1.05–1.82, P?=?0.02; CC vs. TT, OR 2.06, 95 % CI 1.15–3.70, P?=?0.02; CC/CT vs. TT, OR 1.45, 95 % CI 1.03–2.02, P?=?0.03; CC vs. TT/CT, OR 1.56, 95 % CI 1.20–2.03, P?<?0.01). In the stratified analysis by ethnicity, significant associations were also detected in some genetic models. This meta-analysis demonstrates a significant association between the CYP1A1 T3801C polymorphism and cervical neoplasia susceptibility.     

Association between X-ray repair cross-complementing group 1 Arg194Trp polymorphism and colorectal cancer risk

The polymorphism of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, a substitution of Arg to Gln at position 194, has been implicated in the development of colorectal cancer (CRC) in a number of case–control studies with contradictory and inconclusive findings. The current meta-analysis of all currently available publications was conducted to assess the gene susceptibility to CRC and improve our understanding of the CRC pathogenesis. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated by use of fixed-effects model or random-effects model when appropriate. A total of 15 eligible case–control studies with 4,501 cases and 8,038 controls were retrieved after a comprehensive search of the PubMed, Embase, Web of science, and Chinese Biomedicine (CBM) databases up to December 2012. The overall meta-analysis identified a positive but not statistically significant association between the XRCC1 Arg194Trp polymorphism and CRC risk under all genetic contrast models (OR_{Trp vs. Arg}?=?1.07, 95 % CI 0.90–1.26, P _OR?=?0.441; OR_{TrpTrp vs. ArgArg}?=?1.28, 95 % CI 0.91–1.81, P _OR?=?0.163; OR_{ArgTrp vs. ArgArg}?=?1.00, 95 % CI 0.85–1.19, P _OR?=?0.956; OR_{ArgTrp + TrpTrp vs. ArgArg}?=?1.06, 95 % CI 0.90–1.24, P _OR?=?0.502; OR_{TrpTrp vs. ArgArg + ArgTrp}?=?1.11, 95 % CI 0.91–1.34, P _OR?=?0.306). The genotype TrpTrp carriers among Caucasians were more susceptible to CRC, although lack statistical evidence (OR_{TrpTrp vs. ArgArg}?=?2.69, 95 % CI 0.97–7.49, P _OR?=?0.058; OR_{TrpTrp vs. ArgArg + ArgTrp}?=?2.77, 95 % CI 0.99–7.72, P _OR?=?0.051). Interestingly, the XRCC1 Arg194Trp variant was significantly associated with an increased risk of colon cancer. The present meta-analysis suggests that the XRCC1 Arg194Trp polymorphism may modify the risk for CRC, particularly colon cancer. However, the precise genetic association needs to be further estimated in future studies.     

Association between the XRCC3 C241T polymorphism and lung cancer risk in the Asian population

X-ray repair cross-complementing group 3 (XRCC3) plays a vital role in maintaining the stability of genome by homologous recombination repair for DNA double-strand breaks. The genetic polymorphism of XRCC3 C241T has been implicated in lung cancer risk, but the findings across published studies in Asians are inconsistent and inconclusive. To estimate the precise association of XRCC3 C241T polymorphism with lung cancer risk, a meta-analysis of all currently available studies in Asians was performed. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted for eligible studies based on the inclusion criteria. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to assess the association. Besides, subgroup analysis and sensitivity analysis were also performed for further estimation. Seven available studies with a total of 7,398 subjects were finally included into this meta-analysis. The overall ORs indicated that the XRCC3 C241T polymorphism was not associated with a lung cancer risk among Asians in all genetic contrast modes (OR_{T allele vs. C allele}?=?1.08, 95 % CI 0.95–1.24, P _OR?=?0.252; OR_{TT vs. CC}?=?1.30, 95 % CI 0.69–2.45, P _OR?=?0.426; OR_{CT vs. CC}?=?1.07, 95 % CI 0.93–1.24, P _OR?=?0.363; OR_{TT + CT vs. CC}?=?1.08, 95 % CI 0.94–1.24, P _OR?=?0.300; OR_{TT vs. CC + CT}?=?1.29, 95 % CI 0.68–2.43, P _OR?=?0.439). We failed to identify significant association between the XRCC3 C241T polymorphism and risk of lung cancer in Chinese and population-based studies. Interestingly, the pooled ORs in hospital-based studies indicated that the XRCC3 C241T variant carriers were more susceptible to lung cancer (OR_{T allele vs. C allele}?=?1.27, 95 % CI 1.04–1.56, P _OR?=?0.019; OR_{CT vs. CC}?=?1.26, 95 % CI 1.01–1.57, P _OR?=?0.045; OR_{TT + CT vs. CC}?=?1.28, 95 % CI 1.03–1.59, P _OR?=?0.027). Sensitivity analysis confirmed the stability and liability of all results. This meta-analysis suggests that the XRCC3 C241T polymorphism may not exert a risk effect on the lung cancer risk in Asians, although a statistically significant association was observed among the hospital-based studies. Thus, the precise relationship between the XRCC3 C241T variant and lung cancer risk needs further confirmation in future studies with large available data.     

The VDR gene FokI polymorphism and ovarian cancer risk

The polymorphism of vitamin D receptor (VDR) gene is demonstrated to affect the activity of its encoding protein and the subsequent downstream effects mediated by vitamin D. Mutations in VDR gene FokI have been suggested in the development of various cancers. Whether the polymorphism of the VDR gene FokI confers risk to ovarian cancer still remains controversial across the published studies in different ethnicity. The aim of this meta-analysis was to determine the role of VDR gene FokI variant in the susceptibility to ovarian cancer. Six publications with 14 individual case–control studies involving a total of 10,964 subjects were finally included into our study after a comprehensive literature search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association between the VDR gene FokI polymorphism and ovarian cancer risk was estimated under the allelic (T vs. C), homozygous (TT vs. CC), additive (CT vs. CC), recessive (TT vs. CC + CT), and dominant (CT + TT vs. CC) gene models. The overall odds ratios (ORs) for the contrast models of T vs. C, TT vs. CC, CT vs. CC, and CT + TT vs. CC indicated that the VDR gene FokI variant was related to an increased risk of ovarian cancer (OR_{T vs. C}?=?1.09, 95 % confidence interval (CI) 1.03–1.15, P _OR?=?0.004; OR_{TT vs. CC}?=?1.17, 95 % CI 1.04–1.32, P _OR?=?0.011; OR_{CT vs. CC}?=?1.10, 95 % CI 1.01–1.20, P _OR?=?0.027; OR_{CT + TT vs. CC}?=?1.12, 95 % CI 1.03–1.21, P _OR?=?0.007). The stratified analysis among the Caucasians also identified a significant association between the VDR gene FokI polymorphism and the susceptibility to ovarian cancer. The present meta-analysis with large available published data has revealed that the VDR gene FokI polymorphism confers susceptibility to ovarian cancer, particularly among the Caucasian population.     

No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis

The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case–control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (OR_{Met allele vs. Thr allele}?=?1.01, 95 % CI 0.91–1.13, P _OR?=?0.810; OR_{Met/Met vs. Thr/Thr}?=?1.16, 95 % CI 0.88–1.54, P _OR?=?0.281; OR_{Thr/Met vs. Thr/Thr}?=?0.95, 95 % CI 0.86–1.04, P _OR?=?0.240; OR_{Met/Met?+?Thr/Met vs. Thr/Thr}?=?0.97, 95 % CI 0.89–1.06, P _OR?=?0.538; OR_{Met/Met vs. Thr/Thr?+?Thr/Met}?=?1.18, 95 % CI 0.91–1.52, P _OR?=?0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations.     

The polymorphism of EGFR 142285G > A exerts no risk effect on breast cancer

The association between the epidermal growth factor receptor (EGFR) 142285G?>?A polymorphism and the susceptibility to breast cancer is unclear. We conducted a meta-analysis of all published studies to estimate the association of EGFR 142285G?>?A polymorphism and breast cancer risk. Systematic computerized searching of the PubMed, Web of Science, and Wanfang databases was performed for relevant publications. Overall, there were three eligible case–control studies with 1,360 cases and 1,522 controls included into our study. The pooled ORs showed that the EGFR 142285G?>?A variant genotypes did not increase or decrease the risk of breast cancer under the following gene models: A vs. G, OR?=?1.07, 95 % CI 0.96–1.19, P _OR?=?0.240; AA vs. GG, OR?=?1.14, 95 % CI 0.91–1.42, P _OR?=?0.239; GA vs. GG, OR?=?0.99, 95 % CI 0.83–1.17, P _OR?=?0.892; GA?+?AA vs. GG, OR?=?1.03, 95 % CI 0.87–1.21, P _OR?=?0.727; AA vs. GG?+?GA, OR?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.096. The between-study heterogeneity was not significant among all studies. The current meta-analysis showed no evidence for significant association between EGFR 142285G?>?A polymorphism and breast cancer risk. Subsequent studies with large sample size are needed for further elucidation.     

MTHFR C677T polymorphism contributes to the risk for gastric cancer

Methylenetetrahydrofolate reductase (MTHFR) has been demonstrated to be involved in carcinogenesis. Increasing individual studies have investigated the role of MTHFR C677T polymorphism in gastric cancer pathogenesis, but with inconsistent findings. The aim of this study was to clarify the potential association of the MTHFR C677T polymorphism with gastric cancer risk by pooling all available data from published case–control studies. We searched the PubMed, Embase, Web of Science, and Wanfang databases for all relevant publications to date. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated. Stratified analysis and sensitivity analysis were also carried out to estimate the strength of this association. A total of 25 case–control studies with 6,572 cases and 9,584 controls were retrieved. Overall, the ORs under five contrast models indicated that the MTHFR C677T variant was positively associated with gastric cancer risk (OR_{T vs. C}?=?1.21, 95 % CI 1.10–1.34, P _OR?<?0.001; OR_{TT vs. CC}?=?1.47, 95 % CI 1.22–1.76, P _OR?<?0.001; OR_{TC vs. CC}?=?1.20, 95 % CI 1.03–1.40, P _OR?=?0.022; OR_{TT?+?TC vs.?CC}?=?1.27, 95 % CI 1.10–1.47, P _OR?=?0.001; OR_{TT vs.?CC?+?TC}?=?1.29, 95 % CI 1.15–1.46, P _OR?<?0.001). Stratified analyses according to ethnicity and source of controls further confirmed the significant correlations. The current meta-analysis provides strong evidence that the MTHFR C677T polymorphism may be a risk factor for gastric cancer among Asians and Caucasians.     

CYP2E1 T7632A and 9-bp insertion polymorphisms and colorectal cancer risk: a meta-analysis based on 4,592 cases and 5,918 controls

Previous studies suggest that genetic factors play important roles in the development of colorectal cancer. CYP2E1 T7632A and 9-bp insertion polymorphisms may influence the risk of colorectal cancer, but published results are conflicting. We therefore conducted a meta-analysis comprising 9 case–control studies with 4,592 cases and 5,918 controls. Odds ratios (ORs) with 95 % confidence interval (95 % CI) were used to assess the strength of the associations of CYP2E1 T7632A and 9-bp insertion polymorphisms with colorectal cancer. For CYP2E1 T7632A polymorphism, meta-analysis showed that there was no significant association between the CYP2E1 T7632A polymorphism and colorectal cancer risk under all contrast models (A vs. T: OR?=?1.06, 95 % CI 0.88–1.29, P?=?0.528; AA vs. TT: OR?=?0.85, 95 % CI 0.61–1.19, P?=?0.351; AA/TA vs. TT: OR?=?1.08, 95 % CI 0.87–1.34, P?=?0.484; and AA vs. TT/TA: OR?=?0.87, 95 % CI 0.62–1.21, P?=?0.395). For CYP2E1 96-bp insertion polymorphism, meta-analysis showed that there was a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk under the allele contrast model and the dominant contrast model (for the allele contrast model: OR?=?1.20, 95 % CI 1.06–1.36, P?=?0.005; for the dominant contrast model: OR?=?1.25, 95 % CI 1.07–1.45, P?=?0.005). Subgroup analysis by race suggested that there was an obvious association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk in Asians under the codominant contrast model. In conclusion, our meta-analysis demonstrates that there is a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk, and CYP2E1 9-bp insertion polymorphism is a risk factor for developing colorectal cancer.     

EPHX1 A139G polymorphism and lung cancer risk: a meta-analysis

Microsomal epoxide hydrolase 1 (EPHX1) plays an important role in both the activation and the detoxification of polycyclic aromatic hydrocarbons and aromatic amines. Polymorphisms at exon 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. Many studies have investigated the association between EPHX1 A139G polymorphism and lung cancer risk, but the impact of EPHX1 A139G polymorphism on lung cancer risk is not clear owing to the apparent inconsistence among those studies. This study aimed to identify the association between EPHX1 A139G polymorphism and lung cancer risk by performing a meta-analysis. We used the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) to explore the association. Finally, 26 studies with a total of 14,494 subjects were included into this meta-analysis. Meta-analyses of total studies showed the EPHX1 A139G polymorphism was associated with lung cancer risk under three genetic models (OR _{G versus A}?=?1.17, 95 % CI 1.04–1.31, P _OR?=?0.01; OR _{AG versus AA}?=?1.21, 95 % CI 1.06–1.37, P _OR?=?0.004; OR _{AG + GG versus AA}?=?1.22, 95 % CI 1.06–1.39, P _OR?=?0.005). Sensitivity analyses and subgroup analyses further identified the significant association between the EPHX1 A139G polymorphism and lung cancer risk. No evidence of publication bias was observed. Meta-analyses of available data supported the concept of EPHX1 A139G polymorphism as a genetic susceptibility factor for lung cancer.     

Association between the NBS1 Glu185Gln polymorphism and breast cancer risk: a meta-analysis

Nijmegen breakage syndrome 1 (NBS1), a vital DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint, plays a critical role in cellular response to DNA damages and the maintenance of genomic stability. The NBS1 Glu185Gln (NBS1 E185Q, NBS1 8360G>C, rs1805794) polymorphism has been indicated to be involved in the development of cancer, but results of previous individual studies on the association between NBS1 Glu185Gln polymorphism and breast cancer risk remain controversial and inconclusive. Our meta-analysis investigated this association for the first time by pooling the odds ratios with corresponding 95 % confidence intervals (95 % CIs) of all individual publications available to date. Overall, 14 separate studies with 6,642 cases and 7,138 controls were finally included into the present meta-analysis after a comprehensive literature search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 21, 2012. Overall analysis and subgroup analyses by ethnicity and source of controls were performed. Meta-analysis of total studies showed that the NBS1 Glu185Gln variant carriers were not susceptible to breast cancer (OR_{Gln vs. Glu}?=?1.05, 95 % CI 0.80–1.39, P _OR?=?0.719; OR _{Gln/Gln vs. Glu/Glu}?=?0.82, 95 % CI 0.62–1.08, P _OR?=?0.154; OR _{Glu/Gln vs. Glu/Glu}?=?1.00, 95 % CI 0.90–1.13, P _OR?=?0.939; OR_{Gln/Gln + Glu/Gln vs. Glu/Glu}?=?0.96, 95 % CI 0.83–1.11, P _OR?=?0.551; OR_{Gln/Gln vs. Glu/Glu + Glu/Gln}?=?0.84, 95 % CI 0.67–1.05, P _OR?=?0.134). Similar results were observed in heterogeneity-adjusted meta-analysis of all studies. Furthermore, subgroup analyses by ethnicity and source of controls did not identify any appreciable relationship of the NBS1 Glu185Gln polymorphism with breast cancer susceptibility in any populations. Sensitivity analysis by sequentially omitting individual studies confirmed the stability and reliability of our results. Our meta-analysis of currently available data shows no association between the NBS1 Glu185Gln polymorphism and breast cancer risk.     

An increased risk of ovarian cancer associated with polymorphism in BRCC5 gene in Caucasian populations

Several reports on the association between the BRCC5 gene polymorphism and ovarian cancer risk have been published recently, but the estimates of the risk vary widely. We thus performed a meta-analysis in an effort to determine the association. To identify the eligible studies, we searched the PubMed, Embase, and CNKI databases, and reviewed all original studies retrieved as well as their citations. The risk of ovarian cancer was estimated using odds ratio (OR) and its 95 % confidence interval (CI). Meta-analysis of seven comparisons revealed an obvious rise in the risk of ovarian cancer under the CC vs. GG contrast model (OR?=?1.52, 95 % CI?=?1.07–2.16, P _OR?=?0.020). A similar increase was also indicated in the CC vs. GC?+?GG model (OR?=?2.10, 95 % CI?=?1.51–2.93, P _OR?BRCC5 polymorphism may be a candidate modifier of ovarian cancer risk in Caucasians.     

Polymorphism of 8q24 rsl3281615 and breast cancer risk

Several genome-wide association studies on breast cancer have reported similar findings of a new cancer susceptibility locus, 8q24 rsl3281615. Subsequent case–control studies have rapidly investigated the association between the single nucleotide polymorphism of rsl3281615 at chromosome 8q24 and breast cancer risk, but the effect of 8q24 rsl3281615 polymorphism on breast cancer is still unclear due to the inconsistence among those studies. Given the contradictory findings, a meta-analysis was performed to determine the association between 8q24 rsl3281615 polymorphism and breast cancer risk. 12 eligible case–control studies with a total of 42,508 cases and 53,928 controls were finally included into this meta-analysis by searching the PubMed, Embase, and China Biology Medicine (CBM) databases. We estimated the summary odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) to assess this association. Meta-analyses of total 12 studies showed 8q24 rsl3281615 polymorphism was significantly associated with an increased risk of breast cancer in all contrast models (OR_{G vs. A}?=?1.10, 95 % CI 1.05–1.14, P _OR?<?0.001; OR_{GG vs. AA}?=?1.20, 95 % CI 1.11–1.29, P _OR?<?0.001; OR_{AG vs. AA}?=?1.08, 95 % CI 1.05–1.12, P _OR?<?0.001; OR_{GG vs. AA +AG}?=?1.13, 95 % CI 1.07–1.19, P _OR?<?0.001; OR_{GG+AG vs. AA}?=?1.13, 95 % CI 1.07–1.19, P _OR?<?0.001). Meta-analyses of studies with high quality showed that 8q24 rsl3281615 polymorphism was still significantly associated with an increased risk of breast cancer under the five genetic contrast models. Sensitivity analyses by sequential omission of any individual studies and subgroup analyses by ethnicity further identified the significant association between 8q24 rsl3281615 polymorphism and breast cancer risk. Conclusively, this meta-analysis shows a significant association between 8q24 rsl3281615 polymorphism and breast cancer risk.     

Association between NQO1 Pro187Ser polymorphism and esophageal cancer: a meta-analysis

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an important enzyme which can catalyze the two-electron reduction of quinoid compounds into hydroquinones. NQO1 Pro187Ser polymorphism can change the enzymatic activity of NQO1, and it has been proposed to be associated with risk of esophageal cancer. We performed a meta-analysis to examine the association between NQO1 Pro187Ser polymorphism and esophageal cancer. Odds ratio (OR) with a 95 % confidence interval (95 % CI) was used to assess the association. Twelve case–control studies with 1,725 cases with esophageal cancer and 2,341 controls were finally included in the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer (allele model: OR?=?1.24, 95 % CI 1.06–1.46, P _OR?=?0.009; homozygote model: OR?=?1.59, 1195 % CI 1.10–2.30, P _OR?=?0.013; dominant model: OR?=?1.31, 95 % CI 1.05–1.64, P _OR?=?0.018). In the subgroup analysis by ethnicity, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer in Asians but not in Caucasians. Therefore, the meta-analysis suggests that NQO1 Pro187Ser polymorphism is associated with esophageal cancer risk.     

Vascular endothelial growth factor gene polymorphism (-634G/C) and breast cancer risk

The aim of this meta-analysis was to assess if the -634G/C polymorphism represents a predisposition factor for the risk of breast cancer. We included eight published case-control studies, in which a total of 6,175 cancer cases and 6,421 cancer-free controls were included. Pooled ORs and 95 % CIs were calculated by the fixed effects model to evaluate the association of the -634G/C polymorphism and breast cancer risk. When all studies were pooled, we did not find statistical evidence of any significant association with overall breast cancer risk (OR_{BB vs. bb}?=?1.00, 95 % CI?=?0.93–1.07, P?=?0.999; OR_{BB + Bb vs. bb}?=?1.00, 95 % CI?=?0.95–1.05, P?=?0.999; OR_{BB vs. Bb + bb}?=?1.03, 95 % CI?=?0.96-1.09, P?=?0.984; OR_{allele B vs. allele b}?=?1.01, 95 % CI?=?0.97–1.05, P?=?0.998; OR_{Bb vs. bb}?=?0.99, 95 % CI?=?0.92–1.06, P?=?0.992). In further stratified analyses by ethnicity and control source, no significant association was revealed. This study suggests that the -634G/C polymorphism does not appear to represent a risk factor for breast cancer.     

HIF-1α P582S and A588T polymorphisms and digestive system cancer risk—a meta-analysis

Hypoxia-inducible factor-1 (HIF-1) influences cancer progression and metastasis through various mechanisms, and HIF-1α polymorphisms are reportedly associated with many cancers; however, the associations of HIF-1α P582S and A588T polymorphisms with the risk of digestive system cancer remain inconclusive. To understand the role of HIF-1α P582S and A588T genotypes in digestive cancer development, we conducted a comprehensive meta-analysis involving 1,517 cases and 3,740 controls. Overall, the P582S polymorphism was not significantly associated with digestive system cancers in all genotypes. By contrast, the A588T polymorphism was significantly associated with digestive system cancers in the dominant model (TT/AT vs. AA: OR?=?3.17, 95 % CI: 1.21, 8.25; P _{heterogeneity}?<?0.001). In subgroup analysis for cancer types, the two polymorphisms were only associated with increased risk of pancreatic cancer (P582S: SS vs. PP: OR?=?2.51, 95 % CI: 1.31, 4.81; SS vs. PP/PS: OR?=?8.73, 95 % CI: 1.33, 57.1; A588T: TT vs. AA: OR?=?9.30, 95 % CI: 1.12, 77.6; P _{heterogeneity}?=?0.478; TT vs. AA/AT: OR?=?3.14, 95 % CI: 1.99, 4.97; P _{heterogeneity}?=?0.098; TT/AT vs. AA: OR?=?8.65, 95 % CI: 1.05, 71.6; P _{heterogeneity}?=?0.418). According to the source of ethnicity, the P582S and the A588T polymorphisms are both significantly associated with an increased risk of cancer among Caucasians in the homozygote model (SS vs. PP: OR?=?2.41, 95 % CI: 1.24, 4.691; P _{heterogeneity}?=?0.010; TT vs. AA: OR?=?98.6, 95 % CI: 4.37, 2,224; P _{heterogeneity}?=?0.040) and the recessive model (SS vs. PP/PS: OR?=?9.48, 95 % CI: 1.12, 80.3; P _{heterogeneity}?<?0.001; TT vs. AA/AT: OR?=?82.7, 95 % CI: 3.79, 1,802; P _{heterogeneity}?=?0.041). Our findings suggest that the HIF-1α A588T polymorphism is significantly associated with higher cancer risk and the P582S polymorphism is significantly associated with pancreatic cancer risk. Furthermore, the effect of both polymorphisms on digestive system cancer is more pronounced among Caucasians than that among Asians.     

Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case–control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (OR_{Met allele vs. Thr allele}?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.102; OR_{MetMet vs. ThrThr}?=?1.32, 95 % CI 0.93–1.87, P _OR?=?0.121; OR_{ThrMet vs. ThrThr}?=?1.17, 95 % CI 0.94–1.45, P _OR?=?0.150; OR_{MetMet + ThrMet vs. ThrThr}?=?1.20, 95 % CI 0.96–1.51, P _OR?=?0.114; OR_{MetMet vs. ThrThr + ThrMet}?=?1.37, 95 % CI 0.98–1.93, P _OR?=?0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case–control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.     

Association between CD95L polymorphism and cervical cancer risk: evidence from a meta-analysis

Several studies have assessed the association of CD95L polymorphism with cervical cancer risk, but the data lack the power to provide compelling evidence. In this study, we aimed to clarify the association through a meta-analysis. A comprehensive search was conducted in PubMed, Embase, and Web of Science. The fixed-effects model was used to calculate odds ratio (OR) with 95 % confidence intervals (CIs). A total of five papers with six case–control studies were derived and finally included in this meta-analysis. The overall estimate did not reveal any significant association between CD95L ?844C/T polymorphism and cervical cancer risk. Subgroup analysis in Asian population indicated nonsignificant nevertheless potentially increased risk in CC genotype carriers in comparison with the carriers of CT?+?TT genotypes (OR_{CC vs. CT?+?TT}?=?1.16, 95 % CI?=?0.99–1.36, P for heterogeneity?=?0.231). Based on current epidemiological studies, this meta-analysis suggests that CD95L polymorphism may not be a risk factor contributing to cervical cancer development.