Breast Cancer 1 (BRCA1) gene is a well-characterized tumor suppressor gene, mutations of which are primarily found in women with breast and ovarian cancers. BRCA1-associated RING domain 1 (BARD1) gene has also been identified as an important tumor suppressor gene in breast, ovarian, and uterine cancers. Underscoring the functional significance of the BRCA1 and BARD1 interactions, prevalent mutations in the BRCA1 gene are found in its RING domain, through which it binds the RING domain of BARD1. BARD1-BRCA1 heterodimer plays a crucial role in a variety of DNA damage response (DDR) pathways, including DNA damage checkpoint and homologous recombination (HR). However, many mutations in both BARD1 and BRCA1 also exist in other domains that significantly affect their biological functions. Intriguingly, recent genome-wide studies have identified various single nucleotide polymorphisms (SNPs), genetic alterations, and epigenetic modifications in or near the BARD1 gene that manifested profound effects on tumorigenesis in a variety of non-breast and non-gynecological cancers. In this review, we will briefly discuss the molecular functions of BARD1, including its BRCA1-dependent as well as BRCA1-independent functions. We will then focus on evaluating the common BARD1 related SNPs as well as genetic and epigenetic changes that occur in the non-BRCA1-dominant cancers, including neuroblastoma, lung, and gastrointestinal cancers. Furthermore, the pro- and anti-tumorigenic functions of different SNPs and BARD1 variants will also be discussed.

No abstract

Background: Rheumatoid arthritis (RA) is an autoimmune disease that can cause irreversible joint deformities and bone erosions. Criteria to diagnose RA includs many laboratory tests with variable sensitivity and specificity. Sclerostin, a Wnt inhibitor, could be associated with the reduced bone formation in RA. This study aims to measure sclerostin level and its association with RA and its activity.Materials and methods: This study contained fifty-eight RA cases and thirty controls who were age and sex matched. All laboratory tests were conducted on both groups, including sclerostin which was measured by enzyme-linked immunosorbent assay (ELISA). The disease activity was assessed using disease activity scores (DAS28).Results: Our results showed that sclerostin levels were significantly higher in RA patients compared to control (p<0.001) but were significantly lower than RA patients with joint deformities (0.026). Sclerostin levels also correlated with CRP (r=0.328, p=0.012), Anti-CCP (r=0.418, p=0.001), tender joint count (r=0.293, p=0.025), and DAS28 (r=0.26, p=0.047). There was not a significant association with other variables such as ESR, and rheumatoid factor. By using receiver operating characteristic (ROC) curve, the best cut-off value of sclerostin was 249.69 pg/ml which showed (AUC 0.910, sensitivity 87.9%; specificity 93.3%) and [Odd Ratio (OR) Value & P-value: 102, P< 0.0001].Conclusion: Sclerostin can be used in addition to other parameters to diagnose RA as it was associated with RA with good sensitivity and specificity. It was also associated in early joint destruction and tenderness.

No abstract

No abstract