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.     

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.     

The association between two polymorphisms of eNOS and breast cancer risk: a meta-analysis

Breast cancer is one of the most common malignant tumors worldwide. Endothelial nitric oxide synthase (eNOS) plays a key role in breast cancer development. The associations between the two eNOS polymorphisms (E298D rs1799983, −786T>C rs2070744) and breast cancer risk are inconclusive. A meta-analysis was performed in this study. By searching Medline, ISI Web of Knowledge, ScienceDirect, EBSCO, CNKI, and SinoMed database, six case–control studies were collected for the eNOS E298D polymorphism (3,038 cases and 2,508 controls) and three case–control studies were eligible for the eNOS −786T>C polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the two eNOS polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, significantly decreased risk was observed for E298D (for EE vs. DD: OR = 0.74, 95% CI = 0.59–0.94; for ED vs. DD: OR = 0.78, 95% CI = 0.61–0.98; for dominant model: OR = 0.77, 95% CI = 0.61–0.96) and −786T > C (for TT vs. CC: OR = 0.60, 95% CI = 0.42–0.86; for dominant model: OR = 0.66, 95% CI = 0.47–0.94). In the subgroup analysis by ethnicity, significant decreased risks were found for E298D (for EE vs. DD: OR = 0.75, 95% CI = 0.56–0.99) and −786T>C (for TT vs. CC: OR = 0.53, 95% CI = 0.35–0.81; for dominant model: OR = 0.61, 95% CI = 0.41–0.91; for recessive model: OR = 0.70, 95% CI = 0.55–0.91) among Caucasians; significant decreased risks were observed for E298D (for ED vs. DD: OR = 0.12, 95% CI = 0.02–0.96; for dominant model: OR = 0.13, 95% CI = 0.02–1.00) among Asians. In conclusion, this meta-analysis suggests that both eNOS E298D and −786T>C polymorphisms are associated with reduced breast cancer risk.     

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.     

Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects

The A2756G polymorphism in the methionine synthase (MTR) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case–control studies, including 8,438 breast cancer cases and 10,515 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the MTR A2756G polymorphism and breast cancer risk were found for GG versus AA (OR = 0.98, 95% CI: 0.84–1.15), AG versus AA (OR = 0.95, 95% CI: 0.89–1.01), GG/AG versus AA (OR = 0.95, 95% CI = 0.89–1.01), and GG versus AG/AA (OR = 1.00, 95% CI: 0.86–1.17). However, in the stratified analysis, significantly decreased breast cancer risks were found among Europeans (AG versus AA, OR = 0.90, 95% CI = 0.83–0.98; GG/AG versus AA, OR = 0.90, 95% CI = 0.82–0.97) and studies with population-based controls (AG versus AA, OR = 0.93, 95% CI = 0.86–1.00; GG/AG versus AA, OR = 0.93, 95% CI = 0.86–1.00). When stratifying by the menopausal status, no significant result was observed in all genetic models. Taken together, the results suggest that the MTR A2756G polymorphism may contribute to susceptibility to breast cancer among Europeans.     

Lack of association between CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis of 22,090 cases and 28,498 controls

Epidemiological studies have evaluated the association between CYP17 MspA1 polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 35 studies including 22,090 cases and 28,498 controls were identified. Genotype distributions of CYP17 in the controls of all studies were in agreement with Hardy–Weinberg equilibrium (HWE) except for three studies. When all 35 studies were pooled into the meta-analysis, there was no evidence for significant association between CYP17 MspA1 polymorphism and breast cancer risk (for A1/A2 vs. A1/A1: OR = 1.00, 95% CI = 0.96–1.04; for A2/A2 vs. A1/A1: OR = 1.03, 95% CI = 0.97–1.08; for dominant model: OR = 1.01, 95% CI = 0.97–1.05; for recessive model: OR = 1.03, 95% CI = 0.98–1.08). In the subgroup analyses by ethnicity, menopausal status and source of controls, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that CYP17 MspA1 polymorphism is not associated with increased breast cancer risk.     

Screening RAD51C nucleotide alterations in patients with a family history of breast and ovarian cancer

Breast cancer is the most prevalent cancer worldwide. Many published articles have evaluated the association between the transforming growth factor beta 1 (TGFB1) T29C 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. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 12 studies including 10,417 breast cancer cases and 11,455 controls were identified. Overall, no significant associations between the TGFB1 T29C polymorphism and breast cancer risk were found for CC versus TT (OR = 1.00, 95% CI = 0.92–1.09), TC versus TT (OR = 0.98, 95% CI = 0.93–1.05), CC/TC versus TT (OR = 0.99, 95% CI = 0.93–1.05), and CC versus TC/TT (OR = 1.00, 95% CI = 0.93–1.08). In the subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in all genetic models. In conclusion, the present meta-analysis suggests that the TGFB1 T29C polymorphism is not a low-penetrant risk factor for developing breast cancer.     

STK15 F31I polymorphism is associated with breast cancer risk: a meta-analysis involving 25,014 subjects

Published data on the association between STK15 F31I polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, Web of Science, and Chinese Biomedicine Database were searched. Crude ORs with 95% CIs were used to assess the strength of association between the STK15 F31I polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (FI vs. FF; II vs. FF), dominant model (FI + II vs. FF), and recessive model (II vs. FI + FF), respectively. A total of 10 studies including 10,537 cases and 14,477 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with II variant genotype in homozygote comparison and recessive genetic model when all studies were pooled into the meta-analysis (for II vs. FF: OR = 1.23, 95% CI = 1.10–1.37; for recessive model: OR = 1.21, 95% CI = 1.05–1.40). In the subgroup analysis by ethnicity, significantly increased risks were found for II allele carriers among Caucasians (for II vs. FF: OR = 1.24, 95% CI = 1.08–1.43; for recessive model: OR = 1.21, 95% CI = 1.00–1.45); significantly increased risks were also found among Asians for II versus FF (OR = 1.21; 95% CI = 1.01–1.45). In conclusion, this meta-analysis suggests that the STK15 31II allele is a low-penetrant risk factor for developing breast cancer.     

Current evidences on XPC polymorphisms and breast cancer susceptibility: a meta-analysis

Published data on the association between three polymorphisms (Lys939Gln, Ala499Val, and PAT±) of Xeroderma Pigmentosum group C (XPC) 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 11 studies including 5,090 cases and 5,214 controls were involved in this meta-analysis. For XPC Lys939Gln polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.00, 95% CI 0.92–1.10; Gln/Gln vs. Lys/Lys: OR = 0.96, 95% CI 0.84–1.09; dominant model: OR = 0.99, 95% CI 0.91–1.08; and recessive model: OR = 0.97, 95% CI 0.86–1.09). In the subgroup analysis by ethnicity or study design, still no obvious associations were found. For XPC Ala499Val polymorphism, also no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Val/Ala vs. Ala/Ala: OR = 0.91, 95% CI 0.79–1.05; Val/Val vs. Ala/Ala: OR = 1.07, 95% CI 0.80–1.44; dominant model: OR = 0.93, 95% CI 0.81–1.06; and recessive model: OR = 1.11, 95% CI 0.84–1.48). For XPC PAT± polymorphism, obvious associations were found for recessive model when all studies were pooled into the meta-analysis (OR = 1.41, 95% CI 1.05–1.89). In conclusion, this meta-analysis suggests that the XPC PAT± polymorphism allele may be a low-penetrant risk factor for developing breast cancer.     

CYP1B1 Leu432Val polymorphism and colorectal cancer risk among Caucasians: a meta-analysis

Studies investigating the association between cytochrome P450 1B1 (CYP1B1) Leu432Val (432 C/G, rs1056836) polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1B1 polymorphism and CRC were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (GG vs. CC, GC vs. CC), dominant model (GG + GC vs. CC), and recessive model (GG vs. GC + CC). This meta-analysis included ten case–control studies, which included 8,466 CRC cases and 9,301 controls. Overall, the variant genotypes (GG and GC) of the 432 C/G were not associated with CRC risk when compared with the wild-type CC homozygote (GG vs. CC, OR = 1.01, 95% CI = 0.93–1.10; GC vs. CC, OR = 0.97, 95% CI = 0.90–1.04), without any between-study heterogeneity. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 0.98, 95% CI = 0.92–1.05; recessive model, OR = 1.03, 95% CI = 0.96–1.11). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. When stratifying for country, matched control and source of controls, no evidence of significant association was observed in any subgroup. No publication bias was found in the present study. No association is found between the CYP1B1 Leu432Val polymorphism and risk of CRC among Caucasians.     

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.     

Association between two polymorphisms of ABCB1 and breast cancer risk in the current studies: a meta-analysis

Previous epidemiological studies have evaluated the association between the ABCB1 polymorphism and the risk of breast cancer with conflicting results. Hence, we conducted a meta-analysis of the ABCB1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase, and Web of Science databases were searched. A total of eight studies including 3,829 cases and 6,193 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of associations between the ABCB1 C3435T and rs2214102 G>A polymorphisms and risk of breast cancer. Of these studies, only one deviated from Hardy–Weinberg equilibrium. Summary estimates indicated that the ABCB1 C3435T polymorphism was not associated with increased risk of breast cancer in the allele contrast model (T vs. C, pooled OR = 1.15; 95% CI = 0.89–1.48); the co-dominant model (CT vs. CC, OR = 1.12 [0.86–1.46] and TT vs. CC, OR = 1.30 [0.79–2.15]); the dominant model (OR = 0.80 [0.63–1.02]; and the recessive model (OR = 0.83 [0.57–1.22]). In the sensitivity analysis by ethnicity, no statistically significant associations were detected in Asians. However, in Caucasian women the T allele contrast model and the TT genotype were each associated with increased risk: T vs. C, pooled OR (95% CI) = 1.26 (1.04–1.52) and TT vs. CC, OR = 1.48 (1.04–2.11). Accordingly, the dominant model yielded statistically significant results (pooled OR = 0.71, 95% CI: 0.52–0.96) but not with the allele contrast model or the co-dominant model. There was evidence of publication bias (P = 0.02 for recessive model). In conclusion, there is limited evidence to indicate that the ABCB1 C3435T and rs2214102 G>A polymorphisms are associated with increased risk of breast cancer.     

Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta-analysis from 41 studies with 16,480 cases and 22,388 controls

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely reported, but results were inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on the risk of breast cancer, an updated meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of breast cancer was conducted. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to January 2010. Finally, a total of 41 studies with 16,480 cases and 22,388 controls were included, all for C677T polymorphism and 20 with 12,170 cases and 15,865 controls for A1298C polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model, and recessive genetic model, respectively. Subgroup analyses were also performed by ethnicity and menopausal status. With respect to C677T polymorphism, significantly elevated breast cancer risk was found in overall analysis (T vs. C: OR = 1.041, 95% CI = 1.009–1.073; TT vs. CC: OR = 1.132, 95% CI = 1.019–1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014–1.236); in the subgroup analysis by ethnicity, significantly increased risk was found in East Asian population (T vs. C: OR = 1.121, 95% CI = 1.016–1.237; TT vs. CC: OR = 1.331, 95% CI = 1.073–1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058–1.513) but not in Caucasian population; in the subgroup analysis by menopausal status, no statistically significant association was found. With respect to A1298C polymorphism, no significant association with breast cancer risk was demonstrated in overall, ethnicity- and menopausal status-based population. It can be concluded that potentially functional MTHFR C677T polymorphism may play a low penetrance role in the development of breast cancer.     

TNFα ?308 G/A polymorphism is associated with breast cancer risk: a meta-analysis involving 10,184 cases and 12,911 controls

Tumor necrosis factor α (TNFα) is a pleiotropic cytokine which can regulate a wide variety of cellular responses. Low concentrations of TNFα seem to increase tumor growth and progression. The −308 G/A polymorphism in TNFα has been implicated in breast cancer risk but the published data remain inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed by searching PubMed, Web of Science, ScienceDirect, EBSCO, CNKI, and Chinese Biomedicine Database. 11 studies including 10,184 cases and 12,911 controls were collected for TNFα −308 G/A polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the TNFα −308 G/A polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (GG versus AA; GA versus AA), dominant model (GG + GA versus AA), recessive model (GG versus GA + AA), and G allele versus A allele, respectively. Overall, significantly elevated breast cancer risk was found for recessive model (OR = 1.10, 95% CI = 1.04–1.17) and for G allele versus A allele (OR = 1.08, 95% CI = 1.02–1.14). In the subgroup analysis by ethnicity, significantly increased risks were also found among Caucasians for recessive model and for G allele versus A allele (for recessive model: OR = 1.10, 95% CI = 1.04–1.17; for G allele versus A allele: OR = 1.09, 95% CI = 1.03–1.14). However, no significant associations were found among Asians for all genetic models. In conclusion, this meta-analysis suggests that the TNFα −308 G allele is a risk factor for developing breast cancer, especially for Caucasians.     

CCND1 G870A polymorphism and risk for head and neck cancer: a meta-analysis

CCND1 plays a critical role in cell cycle control and may contribute to head and neck cancer. We performed a meta-analysis of eleven case–control studies that examined the association between CCND1 G870A polymorphism and head and neck cancer risk. Overall, no significant association of this polymorphism with head and neck cancer was found (for AA vs. GG: OR = 0.96, 95% CI = 0.59–1.58, P < 0.01 for heterogeneity; for GA vs. GG: OR = 1.00, 95% CI = 0.74–1.35, P < 0.01 for heterogeneity; for the dominant model GA/AA vs. GG: OR = 0.98, 95% CI = 0.69–1.39, P < 0.01 for heterogeneity; for the recessive model AA vs. GG/GA: OR = 0.94, 95% CI = 0.66–1.33, P < 0.01 for heterogeneity). In subgroup analysis by ethnicity, we also did not find any significant association in European and Asians populations. All the results were not materially altered in any genetic model after the studies which did not fulfill Hardy–Weinberg equilibrium were excluded. In conclusion, our meta-analysis strongly suggested that the CCND1 G870A polymorphism is not associated with head and neck cancer risk.     

NBS1 8360G?>?C polymorphism is associated with breast cancer risk: a meta-analysis

NBS1 gene plays an important role in DNA repair. Many epidemiological studies have investigated the association between NBS1 8360G > C polymorphism and breast cancer, however, the results are still controversial. Therefore, we performed a meta-analysis of 10 case–control studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results showed NBS1 8360G > C polymorphism contributed to breast risk in overall populations (for CC vs. GG: OR = 0.75, 95% CI = 0.74–0.98, P = 0.13 for heterogeneity; for the recessive model CC vs. GG/CG: OR = 0.88, 95% CI = 0.77–1.00, P = 0.44 for heterogeneity). In subgroup analysis by ethnicity, no significant association was found in all genetic models. In summary, our meta-analysis strongly suggests the NBS1 8360G > C polymorphism is associated with breast cancer.     

Lack of association between HER2 codon 655 polymorphism and breast cancer susceptibility: meta-analysis of 22 studies involving 19,341 subjects

Epidemiological studies have investigated the association between HER2 codon 655 polymorphism and breast cancer susceptibility. However, the results are still inconclusive. To obtain a more precise estimation of the relationship, this meta-analysis was performed. A total of 22 studies including 9,209 cases and 10,132 controls were collected. The strength of association between HER2 codon 655 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 22 studies were pooled into the meta-analysis, there was no evidence for significant association between HER2 codon 655 polymorphism and breast cancer susceptibility (for Val/Ile vs. Ile/Ile: OR = 1.069, 95% CI = 0.976–1.172; for Val/Val vs. Ile/Ile: OR = 1.191, 95% CI = 0.922–1.538; for dominant model: OR = 1.093, 95% CI = 0.991–1.206; for recessive model: OR = 1.141, 95% CI = 0.902–1.444). In the subgroup analysis by the source of controls and ethnicity, no significant increased risk was found in all genetic models. However, the current results indicated the modest association between the HER2 Ile655Val polymorphism and Asian population (Val/Ile vs. Ile/Ile: OR = 1.207, CI = 1.006–1.450). In summary, the meta-analysis suggests that HER2 codon 655 polymorphism is not associated with the increased breast cancer risk.     

HER2 Ile655Val polymorphism contributes to breast cancer risk: evidence from 27 case–control studies

Proto-oncogene HER2 (also known as erbB-2 or neu) plays an important role in the carcinogenesis and the prognosis of breast cancer. Many epidemiological studies have been conducted to explore the association between the HER2 Ile655Val polymorphism and breast cancer risk. However, inconsistency existed in the results. Therefore, we performed a meta-analysis of 27 published case–control studies including 11,504 cases and 12,538 controls. We assessed the strength of the association by crude odds ratios (ORs) with 95% confidence intervals (CIs) and reached a result that HER2 Ile655Val polymorphism was associated with an increased breast cancer risk in overall populations (for Ile/Val vs. Ile/Ile: OR = 1.05, 95% CI = 1.00–1.12, P = 0.07 for heterogeneity; for the dominant model Ile/Val + Val/Val vs. Ile/Ile: OR = 1.10, 95% CI = 1.01–1.20, P = 0.01 for heterogeneity). In subgroup analysis by ethnicity, we found a significant association among Africans (for Val/Val vs. Ile/Ile: OR = 8.78, 95% CI = 1.94–39.72, P = 0.35 for heterogeneity; for the recessive model Val/Val vs. Ile/Val +Ile/Ile: OR = 8.60, 95% CI = 1.92–38.48, P = 0.31 for heterogeneity) and Asians (for Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01–1.39, P = 0.41 for heterogeneity; for the dominant model Val/Val + Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01–1.38, P = 0.27 for heterogeneity). In conclusion, our meta-analysis suggests that HER2 Ile 655Val polymorphism may contribute to breast cancer risk.     

Lack of association between MnSOD Val16Ala polymorphism and breast cancer risk: a meta-analysis involving 58,448 subjects

Published data on the association between MnSOD Val16Ala 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 MnSOD Val16Ala polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs. Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including 26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no significant associations were found between MnSOD Val16Ala polymorphism and breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs. Val/Val: OR = 1.022, 95% CI = 0.981–1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95% CI = 0.934–1.083; dominant model: OR = 1.013, 95% CI = 0.962–1.066; and recessive model: OR = 0.985, 95% CI = 0.931–1.042). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.     

SULT1A1 R213H polymorphism and breast cancer risk: a meta-analysis based on 8,454 cases and 11,800 controls

The SULT1A1 R213H polymorphism is suggested to be implicated in the development and progression of breast cancer. However, the published findings are inconsistent. We therefore performed a meta-analysis of 8,454 breast cancer cases and 11,800 controls from 14 published case–control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association of the R213H polymorphism with breast cancer risk. Overall, our results suggested that there is no significant relationship between SULT1A1 R213H polymorphism and the risk of breast cancer. However, further ethnic population analysis revealed a significantly increased risk of breast cancer for HH allele carriers among Asians (for HH vs. RR: OR = 2.27, 95% CI = 1.11–4.63, P _{heterogeneity} = 0.63; for the recessive model: OR = 2.03, 95% CI = 1.00–4.41, P _{heterogeneity} = 0.62). Taken together, this meta-analysis suggests that the SULT1A1 R213H may be a low-penetrant risk factor for developing breast cancer in Asian population.