RAD51 G135C polymorphism is associated with breast cancer susceptibility: a meta-analysis involving 22,399 subjects

Several studies have investigated the associations between RAD51 G135C polymorphism and the susceptibility to breast cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 case control studies, including 12,153 cases and 10,245 controls, were selected. Overall, significant decreased risk was found for the additive model (OR = 0.995, 95% CI = 0.991–0.998) and dominant model (OR = 0.994, 95% CI = 0.991–0.998). In the subgroup analysis by ethnicity, statistically significantly decreased risk was found in Asians (additive model: OR = 0.977, 95% CI = 0.954–1.000 and dominant model: OR = 0.981, 95% CI = 0.963–1.000). In conclusion, this meta-analysis suggests that the RAD51 G135C polymorphism is a low-penetrant risk factor for developing breast cancer.     

RAD51 135G>C and TP53 Arg72Pro polymorphisms and susceptibility to breast cancer in Serbian women

Breast cancer is a complex disease with both genetic and environmental factors involved in its etiology. An important role of polymorphisms in genes involved in DNA repair has been reported related to breast cancer risk. We conducted a case–control study in order to investigate the association of RAD51 135G>C and TP53 Arg72Pro polymorphisms with breast cancer in Serbian women.48 BRCA negative women with breast cancer and family history of breast/ovarian cancer (hereditary group), 107 women with breast cancer but without family history of the disease (sporadic group) and 114 healthy women without a history of the disease (control group) were included. Restriction fragment length polymorphism was used for genotyping. Genotype and allelic frequencies, the odds ratio (OR) and the 95 % confidence interval (CI) were calculated as an estimate of relative risk. The Hardy–Weinberg equilibrium was tested using χ² test. Significance was considered for p < 0.05. RAD51 135G>C showed statistically significant association of CC genotype and increased breast cancer risk (OR 10.28, 95 % CI 1.12–94.5) in hereditary group of patients compared to the control group. Regarding the TP53 Arg72Pro, we showed statistical significance for ProPro + ProArg comparing to ArgArg (OR 2.34, 95 %, CI 1.17–4.70) in hereditary compared to sporadic group. RAD51 135G>C contributes to hereditary breast cancer in Serbian population, with CC genotype as a risk factor. We also found that carriers of Pro allele of TP53 codon 72 is related to hereditary cancer comparing to sporadic one, which indicates it as a potential risk factor for hereditary form of disease.     

RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers: evidence from a meta-analysis of 12 studies

A single-nucleotide polymorphism (SNP) in the 5′-untranslated region (UTR) of RAD51, 135G>C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers. A few studies have also investigated the genetic contribution of RAD51 135G>C to the risk of sporadic breast cancers or breast cancer in non-BRCA1/2 carriers, though the results are yet controversial and inconclusive. We, in this study, performed a more precise estimation of the relationship between 135G>C and breast cancer among non-BRCA1/2 mutation carriers by meta-analyzing the currently available evidence from the literature. A total of 12 studies involving 7,065 cases and 6,981 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, there was no evidence for a significant association between 135G>C and breast cancer risk in non-BRCA1/2 mutation carriers (for CC vs. GG: OR = 0.995, 95%CI: 0.741–1.336; for GC vs. GG: OR = 0.959, 95%CI: 0.869–1.057; for dominant model: OR = 0.988, 95%CI: 0.902–1.082; and for recessive model: OR = 1.037, 95%CI: 0.782–1.376). We also performed subgroup analysis by ethnicity (Caucasian) as well as did analysis using the studies fulfilling Hardy–Weinberg equilibrium, and the results did not change. In summary, the present meta-analysis suggests that the RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers.     

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.     

The effect of RAD51 135 G>C and XRCC2 G>A (rs3218536) polymorphisms on ovarian cancer risk among Caucasians: a meta-analysis

Genetic polymorphisms of RAD51 135 G>C and XRCC2 G>A (rs3218536) have been reported to change the risk of ovarian cancer, but the results are controversial. To get a more precise result, a meta-analysis was performed. A comprehensive literature search in PubMed, Excerpta Medica Database, and China National Knowledge Infrastructure was carried out to get case–control studies published up to November 2013. The pooled odds ratio (OR) and its corresponding 95 % confidence interval (CI) were conducted to estimate the effect of RAD51 135 G>C and XRCC2 G>A (rs3218536) polymorphisms on ovarian cancer risk. A total of 13 independent case–control studies with 5,927 cases and 10,303 controls were included in this meta-analysis. There was no significant association between RAD51 135 G>C polymorphism and risk of ovarian cancer. However, the result of total studies indicated the XRCC2 G>A (rs3218536) polymorphism could reduce the risk of ovarian cancer (heterozygote model AG vs. GG: OR?=?0.877, 95 % CI?=?0.770–0.999, P?=?0.048; dominant model AA/AG vs. GG: OR?=?0.864, 95 % CI?=?0.763–0.979, P?=?0.022). The result was still significant after Hardy–Weinberg equilibrium-violating studies were excluded (allele contrast A vs. G: OR?=?0.836, 95 % CI?=?0.74–0.943, P?=?0.004; homozygote model AA vs. GG: OR?=?0.562, 95 % CI?=?0.317–0.994, P?=?0.048; heterozygote model AG vs. GG: OR?=?0.859, 95 % CI?=?0.753–0.98, P?=?0.023; dominant model AA/AG vs. GG: OR?=?0.842, 95 % CI?=?0.74–0.958, P?=?0.009). In the stratified analysis by ethnicity, significantly reduced risk was observed among Caucasians in dominant model (AA/AG vs. GG: OR?=?0.867, 95 % CI?=?0.764–0.984, P?=?0.027). No significant association was found between the RAD51 135G>C polymorphism and the risk of ovarian cancer. Interestingly, XRCC2 G>A (rs3218536) polymorphism might reduce the risk of ovarian cancer. Larger-scale and well-designed studies are needed to further clarify the association.     

Association between FAS 1377G>A polymorphism and breast cancer susceptibility: a meta-analysis

Published studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility were inconclusive. To derive a more precise assessment of the association, a meta-analysis of published studies was performed. PubMed, Embase, and Web of Science were searched for eligible studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility. Five studies with a total of 2,905 cases and 3,090 controls were included into the meta-analysis. Overall, FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer (for AA versus GG: odds ratio (OR)?=?1.39, 95 % confidence interval (95 % CI) 1.12–1.72, P?=?0.003; for AA/GA versus GG: OR?=?1.18, 95 % CI 1.06–1.32, P?=?0.004; for AA versus GG/GA: OR?=?1.28, 95 % CI 1.05–1.56, P?=?0.015). Subgroup analysis by ethnicity found that FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer in Asians (for AA versus GG: OR?=?1.48, 95 % CI 1.16–1.89, P?=?0.001; for AA/GA versus GG: OR?=?1.24, 95 % CI 1.06–1.46, P?=?0.008; for AA versus GG/GA: OR?=?1.35, 95 % CI 1.08–1.69, P?=?0.008), but the association was not found in Caucasians. Therefore, the findings of the meta-analysis suggest that FAS 1377G>A polymorphism is significantly associated with increased susceptibility to breast cancer in Asians.     

BRCA2 N372H polymorphism and breast cancer susceptibility: a meta-analysis involving 44,903 subjects

Published data on the association between BRCA2 N372H polymorphism and breast cancer risk are inconclusive. 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 them. A total of 22 studies including 22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no significant associations were found between BRCA2 N372H polymorphism and breast cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR = 1.01, 95% CI = 0.97–1.05; HH versus NN: OR = 1.05, 95% CI = 0.97–1.13; dominant model: OR = 1.01, 95% CI = 0.98–1.05; and recessive model: OR = 1.05, 95% CI = 0.98–1.13). In the subgroup analysis by ethnicity, still no significant associations were found for Caucasians, Asians, or Africans. When stratified by study design, statistically significantly elevated risk was found for 372H allele based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01–1.21; dominant model: OR = 1.05, 95% CI = 1.00–1.10; recessive model: OR = 1.09, 95% CI = 1.00–1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.     

RAD51C: a novel cancer susceptibility gene is linked to Fanconi anemia and breast cancer

Germline mutations in many of the genes that are involved in homologous recombination (HR)-mediated DNA double-strand break repair (DSBR) are associated with various human genetic disorders and cancer. RAD51 and RAD51 paralogs are important for HR and in the maintenance of genome stability. Despite the identification of five RAD51 paralogs over a decade ago, the molecular mechanism(s) by which RAD51 paralogs regulate HR and genome maintenance remains obscure. In addition to the known roles of RAD51C in early and late stages of HR, it also contributes to activation of the checkpoint kinase CHK2. One recent study identifies biallelic mutation in RAD51C leading to Fanconi anemia-like disorder. Whereas a second study reports monoallelic mutation in RAD51C associated with increased risk of breast and ovarian cancer. These reports show RAD51C is a cancer susceptibility gene. In this review, we focus on describing the functions of RAD51C in HR, DNA damage signaling and as a tumor suppressor with an emphasis on the new roles of RAD51C unveiled by these reports.     

RAD51 135G>C polymorphism and breast cancer risk: a meta-analysis

Mutations in RAD51 gene are believed to be associated with elevated breast cancer risk. However, several case–control studies focusing on the association between RAD51 135G>C and breast cancer risk failed to achieve consensus. To clarify the effect of RAD51 135G>C polymorphism on breast cancer, a meta-analysis was performed. By searching PubMed and EMBASE, a total of 14 case–control studies, containing 12,183 cases and 10,183 controls, were included. The strength of association between RAD51 135G>C polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). When all the eligible studies were pooled into the meta-analysis, an elevated cancer risk was revealed in additive model (OR, 1.34; 95% CI, 1.01–1.78; P = 0.044) and recessive model (OR, 1.37; 95% CI, 1.03–1.82; P = 0.032). In subgroup analyses by ethnicity, BRCA1/2 mutation status, and family history, a significant association was found only among BRCA2 mutation carriers (additive model: OR, 4.92; 95% CI, 1.11–21.83; P = 0.036; recessive model: OR, 4.88; 95% CI, 1.10–21.67; P = 0.037). Sensitivity analysis did not perturb the results. In conclusion, this meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers.     

FASLG T844C polymorphism and susceptibility to breast cancer: a meta-analysis

Many studies were published to assess the association between FASLG T844C polymorphism and susceptibility to breast cancer, but the data were controversial. A meta-analysis was performed to assess the association comprehensively. We performed a comprehensive search in PubMed, Embase, and Web of Science to find eligible studies. Six studies with a total of 6,784 participants were finally included into the meta-analysis. There were a total of 3,382 cases with breast cancer and 3,402 controls in those six studies. Odds ratio (OR) with 95 % confidence interval (95 %CI) was used to evaluate the association. Overall, there was an obvious association between FASLG T844C polymorphism and breast cancer under all four contrast models (for C versus T: OR?=?1.26, 95 %CI 1.05–1.50, P _OR?=?0.011; for CC versus TT: OR?=?1.42, 95 %CI 1.11–1.81, P _OR?=?0.005; for CC versus TT/TC: OR?=?1.41, 95 %CI 1.06–1.88, P _OR?=?0.019; for CC/TC versus TT: OR?=?1.16, 95 %CI 1.01–1.33, P _OR?=?0.038). In the subgroup analysis by ethnicity, there was an obvious association between FASLG T844C polymorphism and breast cancer in Asians, but there was no obvious association in Caucasians. The meta-analysis suggests that there is an association between FASLG T844C polymorphism and susceptibility to breast cancer, especially in Asians.     

Genetic 135G/C polymorphism of RAD51 gene and risk of cancer: a meta-analysis of 28,956 cases and 28,372 controls

The RAD51 gene is essential for the repair of damaged DNA related to tumor development. Although a number of genetic studies have attempted to link the 135G/C polymorphism of RAD51 gene to the risk of cancer, the results were inconclusive. The present study aimed at investigating the pooled association using the more comprehensive meta-analysis. The PubMed, EBSCO, and BIOSIS databases were searched to identify eligible studies which were published in English before March 2014. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95 % confidence interval (CI). Begg’s test was used to measure publication bias. Sensitivity analyses were also performed to assess the stability of the results. A total of 45 eligible studies with 28,956 patients and 28,372 controls were included in this meta-analysis. Overall, significant association was detected between 135G/C polymorphism and increased cancer risk (C allele vs. G allele: OR 1.23, 95 % CI 1.18–1.28; CC vs. GG: OR 2.41, 95 % CI 2.12–2.74; CC vs. CG: OR 3.86, 95 % CI 3.41–4.37; recessive model: OR 3.57, 95 % CI 3.19–4.00). In further stratified analysis, significantly elevated cancer risk was observed among Caucasians but not Asians. Subgroup analysis by different cancers also showed their significant associations in breast cancer, hematologic malignances, ovarian cancer, colorectal cancer and endometrial cancer, but not in head and neck cancer. Our results indicated that the RAD51 135G/C polymorphism was a candidate for susceptibility of cancer. The effect of the variants on the expression levels and the possible functional role of the variants in different cancers should be addressed in further studies.     

Survivin rs9904341 (G>C) polymorphism contributes to cancer risk: an updated meta-analysis of 26 studies

Survivin, a member of the inhibitor of apoptosis protein family, encoded by BIRC5, is involved in the regulation of apoptosis and in cell cycle control. Emerging evidences indicate that polymorphism in BIRC5 promoter (rs9904341) is associated with cancer risk, but the results of individually published studies are inconclusive. Thus, an updated meta-analysis was performed. PubMed was searched for all eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the association strength. Stratified analysis was performed by cancer type, source of control, genotyping method, and ethnicity. A number of 26 studies, including 6,041 cases and 7,567 controls were analyzed in this meta-analysis. Overall, significantly increased cancer risk was associated with survivin rs9904341 polymorphism when all studies were pooled (CC vs. GG: OR?=?1.36, 95 % CI?=?1.09–1.69; P _{heterogeneity}?<?0.001; CC vs GC/GG: OR?=?1.32, 95 % CI?=?1.11–1.57; P _{heterogeneity}?<?0.001). Stratified analysis by cancer type revealed that the survivin rs9904341 polymorphism may increase the risk of colorectal cancer, renal cell cancer, gastric cancer, and bladder cancer. Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians but not Caucasians. In this updated meta-analysis of 26 studies, we conclude that the survivin rs9904341 polymorphism might contribute to risk of various cancers, especially in Asian populations.     

TGF-β1 29T/C polymorphism and breast cancer risk: a meta-analysis involving 25,996 subjects

Transforming growth factor β1 (TGF-β1) is a cytokine, playing an important role in controlling cell proliferation and differentiation involved in breast cancer. It was reported the 29T/C polymorphism in TGF-β1 has been implicated in breast cancer risk. However, studies on the association between this polymorphism and breast cancer remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 10,341 cases and 15,655 controls from fifty published case-control studies was performed. Our analysis suggested that 29T/C has no association with a trend of breast cancer risk when using both dominant [odds ratio (OR) = 1.01, 95% confidence intervals (CI) 0.96–1.07] and recessive models (OR = 0.98, 95% CI 0.89–1.08) to analyze the data. In ethnic subgroups analysis, 29T/C also did not appear to be risk factors for breast cancer. However, larger scale primary studies are required to further evaluate the interaction of TGF-β1 29T/C polymorphism and breast cancer risk in specific populations.     

TGFB1 L10P polymorphism is associated with breast cancer susceptibility: evidence from a meta-analysis involving 47,817 subjects

Published data on the association between TGFB1 L10P polymorphism 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 them. A total of 30 studies including 20,401 cases and 27,416 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TGFB1 10P allele when all studies were pooled into the meta-analysis (LP vs. LL: OR = 1.046, 95% CI = 1.003–1.090; dominant model: OR = 1.052, 95% CI = 1.012–1.095). In the subgroup analysis by ethnicity, statistically significantly elevated risk was found in Caucasians (dominant model: OR = 1.045, 95% CI = 1.001–1.091). When stratified by study design, statistically significantly elevated risk was found based on population-based studies (dominant model: OR = 1.076, 95% CI = 1.019–1.136). In conclusion, this meta-analysis suggests that the TGFB1 10P allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.     

Lack of association of CYP1A2-164 A/C polymorphism with breast cancer susceptibility: a meta-analysis involving 17,600 subjects

Published data on the association between cytochrome P-450 1A2 (CYP1A2)-164 A/C polymorphism 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 CYP1A2-164 A/C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC versus AA, CC versus AA), dominant model (CC + AC versus AA), and recessive model (CC versus AA + AC), respectively. A total of 9 studies including 7,580 cases and 10,020 controls were involved in this meta-analysis. Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (AC versus AA: OR = 1.02, 95% CI = 0.92–1.13; CC versus AA: OR = 1.17, 95% CI = 0.83–1.64; dominant model: OR = 1.07, 95% CI = 0.93–1.23; and recessive model: OR = 1.13, 95% CI = 0.82–1.55). In the subgroup analysis by ethnicity or source of controls, there was still no significant association detected in all genetic models. In conclusion, upto date, there is still no enough evidence to indicate the association of CYP1A2-164 A/C polymorphism and breast cancer development.     

No association between CYP17 T-34C polymorphism and breast cancer risk: a meta-analysis involving 58,814 subjects

Breast cancer is one of the most common malignant tumors worldwide. To date, many articles have evaluated the association between Cytochrome P450c17 (CYP17) T-34C polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. By searching Medline, ISI Web of Knowledge, Cochrane, ScienceDirect, EBSCO, CNKI, and SinoMed databases, 43 studies including 26,008 cases and 32,806 controls were collected for CYP17 T-34C polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between CYP17 T-34C polymorphism and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, no significant associations between CYP17 T-34C polymorphism and breast cancer susceptibility were found for TT versus CC (OR = 0.96; 95% CI: 0.89–1.05), TC versus CC (OR = 0.97; 95% CI: 0.89–1.06), TT + TC versus CC (OR = 0.97; 95% CI: 0.89–1.05) and TT versus TC + CC (OR = 0.98; 95% CI: 0.93–1.03). In the stratified analysis by ethnicity, menopausal status, and sources of controls, significant associations were still not detected in all genetic models. In conclusion, this meta-analysis strongly suggests that CYP17 T-34C polymorphism is not associated with breast cancer risk.     

IGFBP3 A-202C polymorphism and breast cancer susceptibility: a meta-analysis involving 33,557 cases and 45,254 controls

Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism and breast cancer risk are inconclusive. 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 them. A total of 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02–1.11; dominant model: OR = 1.04, 95% CI = 1.00–1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00–1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01–1.10; dominant model: OR = 1.04, 95% CI = 1.00–1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02–1.78; recessive model: OR = 1.38, 95% CI = 1.05–1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01–1.11; dominant model: OR = 1.03, 95% CI = 1.00–1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer.     

MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls

Published data on the association between MTHFR C677T polymorphism 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 MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01–1.23; dominant model: OR = 1.04, 95% CI = 1.00–1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04–1.35; recessive model: OR = 1.15, 95% CI = 1.03–1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02–1.38; recessive model: OR = 1.17, 95% CI = 1.05–1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02–1.23; dominant model: OR = 1.11, 95% CI = 1.01–1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.