Mutations in exon region of BRCA1‐related RING domain 1 gene and risk of breast cancer

Abstract

Background BRCA1‐associated RING Domain 1 (BARD1) is an important gene related to breast cancer development. However, the role of BARD1 mutations in breast cancer remains inconclusive. This study is to investigate the relationship between exon mutations of BARD1 gene and the risk of early‐onset breast cancer. Methods Totally, 60 cases of early‐onset breast cancer patients (age 30–40 years) and 240 healthy women (age 30–40 years) were enrolled. Exon mutations of BARD1 were detected and analyzed by direct sequencing and SNaPshot. Results The risk of breast cancer was increased by 3.475 times in carriers with deletion mutation at rs28997575 site of BARD1 (aOR1 = 3.475, 95%CI = 1.302–9.276) (p = 0.013). The risk of breast cancer in carriers with GC genotype at rs2229571 site of BARD1 was reduced by 72.6% (aOR1 = 0.274, 95%CI = 0.134–0.562) (p = 0.001), and that in carriers with CC genotype was reduced by 82.8% (aOR1 = 0.172, 95%CI = 0.076–0.392) (p = 0.001). After stratification with family history, the difference of rs2229571 site mutation genotype was statistically significant (OR = −2.169, 95%CI = 0.016–0.828, p = 0.032). Additionally, the frequency distribution of breast cancer family history in the case group (15%) was significantly more than that in the control group (6.7%) (p = 0.037). Conclusion The deletion mutation at rs28997575 locus of the BARD1 gene can significantly increase the risk of breast cancer. The mutation genotype of rs2229571 locus can significantly reduce the risk of breast cancer. Family history is associated with BARD1 gene polymorphism. A family history of breast cancer may be a risk factor for breast cancer.

BARD1 mystery: tumor suppressors are cancer susceptibility genes

“…B & C Represent the high expression of BARD1 gene is significantly associated with shorter relapse free survival (RFS) and distant metastases free survival (DMFS), P = 1.3^-16 and P = 0.029, respectively. Source: The Kaplan-Meier Plotter, ( https://kmplot.com/analysis/ ) [ 71 ] …”

“…F BARD1-BLM gene signuture expression level in correlation with histological grades, G1 (239), G2 (677), and G3 (495), by GOBO. Source: The Kaplan-Meier Plotter, ( https://kmplot.com/analysis/ ) [ 71 ]. Gene expression-based Outcome for Breast cancer (GOBO) online database ( http://co.bmc.lu.se/gobo/ ) [ 60 ] …”

“…Source: THE HUMAN PROTEIN ATLAS online tool ( www.proteinatlas.org ) [ 62 ], https://www.proteinatlas.org/ENSG00000138376-BARD1/pathology . The Kaplan-Meier Plotter, ( https://kmplot.com/analysis/ ) [ 71 ] …”

“…Interestingly, most of the variants’ carriers have a strong family history of breast cancer compared to the control group. Thus, highlighting the substantial involvement of breast cancer positive family history increased the risk of genetic predisposition to breast cancer, particularly in BARD1 polymorphism carriers [ 71 ]. Likewise, in a large pooled analytical study of both breast cancer (48,000 cases) and ovarian cancer (20,800 cases), many pathogenic variants (PVs) of the BARD1 gene were cataloged.…”

The Fundamental Role of BARD1 Mutations and Their Applications as a Prognostic Biomarker for Cancer Treatment

“…Remarkably, compared to the control group, the majority of variant carriers have a long family history of breast cancer. Highlighting the significant contribution of breast cancer-positive family history to the elevated risk of breast cancer due to genetic predisposition, especially in BARD1 polymorphism carriers [69]. Likewise, several pathogenic variants (PVs) of the BARD1 gene were compiled in a sizable pooled analytical research of both breast cancer (48,000 cases) and ovarian cancer (20,800 cases).…”