Association of the MTHFR C677T polymorphism with primary brain tumor risk

Methylenetetrahydrofolate reductase (MTHFR) gene plays key roles not only in folate metabolism but also in carcinogenesis. The single nucleotide polymorphism MTHFR C677T has been indicated in the development of various tumors. The effect of the MTHFR C677T polymorphism on brain tumors remains poorly understood. We performed the present meta-analysis and aimed to provide a better understanding of the pathogenesis of brain tumors. A literature search of the PubMed, Embase, Web of Science, and Wanfang databases was carried out for potential relevant publications. We calculated the pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) to assess the association of MTHFR C677T with the susceptibility to brain tumors. We also performed stratified analysis and sensitivity analysis to further estimate the genetic association. All statistical analyses were conducted by the use of STATA 11.0 (STATA Corporation, College Station, TX, USA). Eight case–control studies involving a total of 3,059 cases and 3,324 controls were retrieved according to the inclusion criteria. The overall ORs suggested that the MTHFR C677T variant can exert a risk effect on brain tumor development under the following contrast models (OR_TC vs.?CC?=?1.14, 95 % CI 1.02–1.27, P _OR?=?0.018; OR_{TT?+?TC vs.?CC}?=?1.23, 95 % CI 1.01–1.51, P _OR?=?0.043). No significant correlation was identified among the Caucasians, but not among the Asians. In addition, the TC genotype carriers were more susceptible to meningioma when compared with the CC genotype carriers (OR_TC vs.?CC?=?1.38, 95 % CI 1.15–1.65, P _OR?<?0.001). The MTHFR C677T polymorphism seemed to exert no effect on glioma risk. The current meta-analysis firstly provides evidence that the MTHFR C677T polymorphism may modify the risk for brain tumors, particularly meningioma. The role of the MTHFR C677T variant in brain tumor pathogenesis across diverse ethnicities needs further elucidation by more future studies with large sample size.     

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.     

Association between MTHFR 677C>T polymorphism and risk of gliomas: evidence from a meta-analysis

Folate metabolism plays an important role in carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a genetic alteration in an enzyme involved in folate metabolism, but its effect on risk of gliomas is still uncertain. To shed some light on these contradictory results from previous studies, we performed a meta-analysis of published data investigating the association between MTHFR 677C>T polymorphism and risk of gliomas. PubMed, Embase, and Web of Science databases were searched for eligible case–control studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of this association. Ten individual case–control studies from six publications with a total of 1,786 cases and 2,076 controls were included into this meta-analysis. There was no obvious heterogeneity under all comparison models of this meta-analysis. Meta-analysis of those ten studies showed that there was no obvious association between MTHFR 677C>T polymorphism and risk of gliomas under all five genetic models (for T versus C, OR?=?1.00, 95 % CI 0.90–1.12, P _OR?=?0.959; for TT versus CC, OR?=?1.02, 95 % CI 0.82–1.27, P _OR?=?0.870; for CT versus CC, OR?=?1.02, 95 % CI 0.89–1.18, P _OR?=?0.733; for TT+CT versus CC, OR?=?1.02, 95 % CI 0.90–1.16, P _OR?=?0.781; for TT versus CT+CC, OR?=?0.99, 95 % CI 0.81–1.21, P _OR?=?0.902). There was also no obvious association between MTHFR 677C>T polymorphism and risk of gliomas in the sensitivity and subgroup analyses of Caucasians. There was no risk of publication bias in this meta-analysis. The evidence from our meta-analysis supports that there is no association between MTHFR 677C>T polymorphism and risk of gliomas.     

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 NQO1 C609T polymorphism and hepatocellular carcinoma risk

NAD(P)H quinine oxidoreductase 1 (NQO1) enzyme plays a crucial role in the protection against oxidative stress. The polymorphism of NQO1 C609T has been implicated in the development of hepatocellular carcinoma (HCC). However, the findings were inconsistent due to different ethnicity, sample size, and source of controls in individual studies. To better estimate the association of NQO1 C609T polymorphism with HCC risk, we performed a meta-analysis of all currently available studies on the susceptibility to HCC. The meta-analysis included three independent studies with a total of 1, 595 subjects. The association was assessed under five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of HCC (OR_{T vs. C}?=?1.47, 95 % CI 1.07–2.00, P _OR?=?0.016; OR_{TT vs. CC}?=?2.06, 95 % CI 1.06–3.98, P _OR?=?0.032; OR_{TC vs. CC}?=?1.33, 95 % CI 1.06–1.67, P _OR?=?0.012; OR_{TT?+?TC vs. CC}?=?1.46, 95 % CI 1.19–1.81, P _OR?TT vs. CC?+?TC?=?1.62, 95 % CI 1.25–2.09, P _OR?NQO1 C609T variant allele and genotypes are more susceptible to HCC, particularly for Asians.     

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.     

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.     

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 the P53 codon 72 polymorphism and nasopharyngeal cancer risk

The P53 codon 72 polymorphism has been identified as a critical biomarker in modifying the risk of nasopharyngeal cancer (NPC). Many studies have investigated the association between the polymorphism of P53 codon 72 and NPC risk; however, the findings across the published studies are inconsistent and inconclusive. To acquire a more precise assessment for this association, we conducted an updated meta-analysis. The PubMed, Embase, Web of Science, and Wanfang databases were searched for relevant case–control studies. Totally, seven independent publications with 1,133 cases and 1,678 controls were retrieved. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated. Increased risk of NPC was observed among individuals carrying the variant allele and genotypes of P53 codon 72 (OR _{Pro vs. Arg}?=?1.32, 95 % CI 1.18–1.47, P _OR?<?0.001; OR _{ProPro vs. ArgArg}?=?1.90, 95 % CI 1.51–2.39, P _OR?<?0.001; OR _{ProArg + ProPro vs. ArgArg}?=?1.33, 95 % CI 1.13–1.57, P _OR?=?0.001; OR _{ProPro vs. ArgArg + ProArg}?=?1.65, 95 % CI 1.35–2.01, P _OR?<?0.001). Stratified analyses by ethnicity and source of controls also identified this significant relationship in Asians, Caucasians, and hospital-based case–control studies. There was no publication bias risk in our study. The updated meta-analysis supports the evidence that the polymorphism of P53 codon 72 is a risk factor for the development of NPC among the populations of both Asian and Caucasian.     

P53 codon 72 polymorphism and lung cancer risk: evidence from 27,958 subjects

The role of p53 codon 72 polymorphism in the development of lung cancer remains obscure due to inconsistent findings of individual case–control studies published to date. A meta-analysis was conducted to better estimate the association between the p53 codon 72 variant and lung cancer risk. All relevant publications from the PubMed, Embase, Web of Science, and Wanfang databases were retrieved. Based on the inclusion criteria, 39 publications involving 44 independent case–control studies were finally included into this meta-analysis. Data were extracted and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated. The overall pooled ORs showed no significant relationship of the p53 codon 72 polymorphism with increased or decreased risk of lung cancer in all gene contrast models (OR _{Pro vs. Arg}?=?1.04, 95 % CI?=?0.96–1.13, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg}?=?1.07, 95 % CI?=?0.91–1.25, P _OR?<?0.001; OR _{Arg/Pro vs. Arg/Arg} =1.04, 95 % CI?=?0.94–1.15, P _OR?<?0.001; OR _{Pro/Pro + Arg/Pro vs. Arg/Arg}?=?1.04, 95 % CI?=?0.94–1.16, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg + Arg/Pro}?=?1.07, 95 % CI?=?0.93–1.23, P _OR?<?0.001). According to the ethnicity, no significant association was observed in subgroup analyses of the Asians, Caucasians, Africans and the mixed population. Similar finding was found in subgroup analyses of hospital-based and population-based studies. Concerning the histological types of lung cancer, the p53 codon 72 variant exerts risk effect on the lung carcinogenesis in patients with adenocarcinoma (OR _{Arg/Pro vs. Arg/Arg}?=?1.10, 95 % CI?=?1.00–1.22, P _OR?=?0.048). Additionally, subgroup analysis by the smoking status demonstrated that the p53 codon 72 variant seemed to play a protective role in lung carcinogenesis among the non-smokers but not the smokers in the contrast model of Arg/Pro vs. Arg/Arg (OR _{Arg/Pro vs. Arg/Arg}?=?0.71, 95 % CI?=?0.50–1.00, P _OR?=?0.049). The present meta-analysis suggests the p53 codon 72 polymorphism may weakly modify the risk for lung cancer among the adenocarcinoma patients and non-smokers. Nevertheless, this association needs further confirmation in future studies with high quality.     

Role of IL-17F T7488C polymorphism in carcinogenesis: a meta-analysis

Previous case-control studies on the association of interleukin-17F (IL-17F) T7488C polymorphism and cancer risk have yielded conflicting and inconclusive findings. We performed a meta-analysis by pooling all currently available data to acquire a more precise estimation of the association. A comprehensive literature screening from the PubMed, Embase, Web of Science, and Wanfang databases was performed for eligible publications without language restrictions. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CIs) were calculated. According to the inclusion criteria, a total of nine case-control studies with 3,034 cases and 3,694 controls were included. Overall, the pooled ORs showed that IL-17F T7488C polymorphism was associated with neither increased nor decreased risk of cancer. However, the IL-17F T7488C polymorphism exerted risk effect on cancer in population-based case-control studies when stratifying analysis by source of controls (C vs T OR?=?1.24, 95 % CI, 1.10–1.40, pooled OR (P_OR)?OR?=?0.001; CC + TC vs TT OR?=?1.29, 95 % CI, 1.12–1.48, P_OR?OR?OR?OR?相似文献   

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.     

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.     

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.     

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.     

P53 codon 72 Arg/Pro polymorphism and glioma risk: an updated meta-analysis

P53 codon 72 Arg/Pro is a C/G variation upstream of the p53 gene on human chromosome 17p13. Many case–control studies have investigated the association between p53 codon 72 Arg/Pro polymorphism and glioma risk but provided inconsistent findings. To better understand the pathogenesis of glioma, we performed the current meta-analysis by pooling data from all available individual studies. According to the inclusion criteria, ten independent publications with 11 case–control studies were included into this meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the effect of p53 codon 72 Arg/Pro variant on the development of glioma. Overall, no appreciable correlation was observed among the total studies in all gene models (OR_{Pro allele vs. Arg allele}?=?1.04, 95 % CI?=?0.90–1.20, P _OR?=?0.581; OR_{Pro/Pro vs. Arg/Arg}?=?0.95, 95 % CI?=?0.80–1.14, P _OR?=?0.614; OR_{Pro/Arg vs. Arg/Arg}?=?1.01, 95 % CI?=?0.79–1.29, P _OR?=?0.993; OR_{Pro/Arg + Pro/Pro vs. Arg/Arg}?=?1.03, 95 % CI?=?0.82–1.29, P _OR?=?0.799; OR_{Pro/Pro vs. Arg/Arg + Pro/Arg}?=?1.02, 95 % CI?=?0.86–1.22, P _OR?=?0.785). In stratified analyses by ethnicity, source of controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not alter the risk for glioma in population-based, hospital-based, astrocytoma, and oligodendroglioma studies among Caucasian. Interestingly, the Pro/Pro genotype seemed to be negatively associated with the glioma risk among patients with glioblastoma (OR_{Pro/Pro vs. Arg/Arg}?=?0.68, 95 % CI?=?0.48–0.95, P _OR?=?0.026). Our study suggests that the polymorphism of p53 codon 72 Arg/Pro may play a protective role in the development of glioblastoma. The relationship of p53 codon 72 Arg/Pro polymorphism with the susceptibility to glioma needs further estimation by more individual studies with high quality across ethnicities.     

Significant association between MTHFR C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis

Previous studies investigated the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hepatocellular carcinoma risk, but the impact of MTHFR C677T polymorphism on hepatocellular carcinoma was still unclear, owing to the obvious inconsistence from those studies. This study aimed to quantify the strength of the association between MTHFR C677T polymorphism and hepatocellular carcinoma risk by performing a meta-analysis. We searched the PubMed and Wanfang databases for studies on the association between MTHFR C677T polymorphism and hepatocellular carcinoma risk. We estimated the pooled odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) to assess the association. Fifteen studies with 8,625 participants were finally included into the meta-analysis. Meta-analyses of total 15 studies suggested that MTHFR C677T polymorphism was significantly associated with an increased risk of hepatocellular carcinoma under two main genetic models (for TT versus CC, OR?=?1.19, 95 % CI 1.03–1.37, P?=?0.016; for TT versus CT/CC, OR?=?1.14, 95 % CI 1.01–1.28, P?=?0.032). Subgroup meta-analyses suggested that MTHFR C677T polymorphism was associated with an increased risk of hepatocellular carcinoma in Asians, but not in Caucasians. Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of hepatocellular carcinoma.     

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 between cytochrome P450 1A1 MspI polymorphism and endometrial cancer risk: a meta-analysis

Many studies proposed that cytochrome P450 1A1 (CYP1A1) MspI polymorphism may be associated with endometrial cancer risk, but the findings from previous studies reported conflicting results. A meta-analysis of all relevant studies was performed to get a comprehensive assessment of the association between CYP1A1 MspI polymorphism and endometrial cancer risk. Eligible studies were searched in PubMed and China National Knowledge Infrastructure databases. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association. Twelve studies with a total of 2,111 cases and 2,894 controls were finally included into the meta-analysis. Overall, meta-analysis of a total of 12 studies showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk (OR_{C vs. T}?=?0.97, 95 % CI 0.77–1.22, P _OR?=?0.808; OR_{CC vs. TT}?=?1.00, 95 % CI 0.57–1.76, P _OR?=?0.994; OR_{CC vs. TT/TC}?=?0.88, 95 % CI 0.65–1.20, P _OR?=?0.425; OR_{CC/TC vs. TT}?=?0.98, 95 % CI 0.74–1.29, P _OR?=?0.861). Subgroup analyses by ethnicity further showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk in both Caucasians and Asians. There was no obvious risk of publication bias. Therefore, the meta-analysis suggests that CYP1A1 MspI polymorphism is not associated with endometrial cancer risk.     

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.