Lack of association between BARD1 Cys557Ser variant and breast cancer risk: a meta-analysis of 11,870 cases and 7,687 controls

Ding, Derong; Zhang, Ying; Ma, Wenxue; He, Xiaofeng; Wang, Wei; Yu, Honglin; Guo, Yubo; Wen-ling, Zheng

doi:10.1007/s00432-011-1006-0

Cited by 10 publications

(12 citation statements)

References 33 publications

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“…Moreover, some non-synonymous polymorphisms (e.g., cys557Ser, Arg378Ser, Val507Met, and Pro24Ser) in the BARD1 gene have been also frequently investigated for their association with cancer susceptibility, and studies mainly involved breast cancer (Morris et al, 2006, Onay et al, 2006, Stacey et al, 2006, Vahteristo et al, 2006, Guenard et al, 2009, Ding et al, 2011, Sun et al, 2012), neuroblastoma (Capasso et al, 2009, Capasso et al, 2013), and cervical cancer (Zhou et al, 2009). Nonetheless, the associations between these BARD1 SNPs and cancer susceptibility have been often paradoxical.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is critical that all association studies consider external validity issues and candidly state the populations to which the results can be applied. Several meta-analyses were undertaken to reevaluate such associations (Ding et al, 2011, Liu et al, 2015). Ding et al reported a lack of association between BARD1 Cys557Ser polymorphism and breast cancer risk in a pooled analysis comprising 11,870 cases and 7687 controls in 2011 (Ding et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Several meta-analyses were undertaken to reevaluate such associations (Ding et al, 2011, Liu et al, 2015). Ding et al reported a lack of association between BARD1 Cys557Ser polymorphism and breast cancer risk in a pooled analysis comprising 11,870 cases and 7687 controls in 2011 (Ding et al, 2011). Liu et al collected 10 case-control studies in 2015 (Liu et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility

Zhu

Xiong

et al. 2017

EBioMedicine

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BRCA1-associated RING domain protein 1 (BARD1) is a tumor suppressor, which forms a heterodimer with BRCA1. Three BARD1 gene polymorphisms (rs7585356 G > A, rs6435862 T > G and rs3768716 A > G) were initially identified as high-risk neuroblastoma susceptibility loci by a previous GWAS. Because of the general tumor-suppressing function of BARD1, we hypothesized that these BARD1 gene polymorphisms might modify the susceptibility to nephroblastoma. We genotyped these polymorphisms in 145 cases and 531 controls using Taqman methods. Out of three polymorphisms, only the rs7585356 G > A polymorphism was significantly associated with increased susceptibility to nephroblastoma [AA vs. GG: adjusted odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.01–3.12]. Combined analysis of three polymorphisms indicated that subjects with 3 risk genotypes exhibited significantly elevated nephroblastoma risk, when compared with subjects with 0–2 risk genotypes (adjusted OR = 1.72, 95% CI = 1.02–2.89). Stratified analysis revealed that in term of clinical stage, rs7585356 AA carriers were associated with increased risk of developing clinical stage I + II nephroblastoma. The presence of three risk genotypes was significantly associated with nephroblastoma risk in females and clinical stage I + II nephroblastoma. Our results suggested that BARD1 rs7585356 G > A may be associated with nephroblastoma risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility

Zhu

Xiong

et al. 2017

EBioMedicine

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“…The role of germline BARD1 mutations in the development of BC is also unclear . Germline BARD1 mutations in those with suspected hereditary BC have been identified but an associated increased relative risk for BC has not been demonstrated .…”

Section: Discussionmentioning

confidence: 99%

Challenges in Interpreting Germline Mutations in BARD1 and ATM in Breast and Ovarian Cancer Patients

et al. 2017

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Next-generation sequencing promotes identification of mutations in non-BRCA1/2 genes in hereditary cancer families. The contribution of mutations in moderate penetrance genes to hereditary cancer risk is not well established. Here, we report a family with early onset breast and fallopian tube cancer that was identified as carrying germline mutations in BARD1 and ATM genes. Loss of heterozygosity studies suggest a causative role of the BARD1 mutation in the development of primary peritoneal cancer, but fail to confirm an association between germline ATM mutations and breast cancer development in this family. Complexities in interpreting implications of mutations in moderate-risk cancer susceptibility genes are discussed.

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“…However, p.C557S is functional in HDR [Laufer et al., ] and in subsequent studies has been shown to have similar allele frequencies in individuals from breast cancer families and controls [Vahteristo et al., ; Ratajska et al., ]. Furthermore, case‐control studies in sporadic breast cancer studies showed no evidence of increased risk [Ding et al., ]. Thus, data suggests that this variant is likely neutral/benign.…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks

et al. 2015

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Genes associated with hereditary breast and ovarian cancer (HBOC) are often sequenced in search of mutations that are predictive of susceptibility to these cancer types, but the sequence results are frequently ambiguous due to detection of missense substitutions for which the clinical impact is unknown. The BARD1 protein is the heterodimeric partner of BRCA1 and is included on clinical gene panels for testing for susceptibility to HBOC. Like BRCA1, it is required for homology-directed DNA repair (HDR). We measured the HDR function of 29 BARD1 missense variants, 27 culled from clinical test results and two synthetic variants. 23 of the assayed variants were functional for HDR; of these, four are known neutral variants. Three variants showed intermediate function, and three others were defective in HDR. When mapped to BARD1 domains, residues crucial for HDR were located in the N- and C- termini of BARD1. In the BARD1 RING domain, critical residues mapped to the zinc-coordinating amino acids and to the BRCA1-BARD1 binding interface, highlighting the importance of interaction between BRCA1 and BARD1 for HDR activity. Based on these results, we propose that the HDR assay is a useful complement to genetic analyses to classify BARD1 variants of unknown clinical significance.

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Lack of association between BARD1 Cys557Ser variant and breast cancer risk: a meta-analysis of 11,870 cases and 7,687 controls

Abstract: This meta-analysis strongly suggests that BARD1 Cys557Ser mutation is not associated with increased breast cancer risk.

Cited by 10 publications

References 33 publications

BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility

BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility

Challenges in Interpreting Germline Mutations in BARD1 and ATM in Breast and Ovarian Cancer Patients

Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks

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