Population frequencies of pathogenic alleles of BRCA1 and BRCA2 : analysis of 173 Danish breast cancer pedigrees using the BOADICEA model

AbstractThe Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) calculates the probability that a woman carries a pathogenic variant inBRCA1 orBRCA2 based on her pedigree and the population frequencies of pathogenic alleles ofBRCA1 (0.0006394) andBRCA2 (0.00102) in the United Kingdom (UK). BOADICEA allows the clinician to define the population frequencies of pathogenic alleles ofBRCA1 andBRCA2 for other populations but only includes preset values for the Ashkenazy Jewish and Icelandic populations. Among 173 early-onset breast cancer pedigrees in Denmark, BOADICEA discriminated well between carriers and non-carriers of pathogenic variants (area under the receiver operating characteristics curve: 0.81; 95% CI 0.74 –0.86) but underestimated the frequency of carriers of pathogenic variants inBRCA1 orBRCA2 as measured by the observed-to-expected ratio (O/E 1.83; 95% CI 1.18 –2.84). This reflects findings from older studies of BOADICEA in UK, German, Italian, and Chinese populations, all accounting for the different calibration for different carrier probabilities. To improve the performance of BOADICEA for non-UK populations, we developed a method to derive population frequencies of pathogenic alleles ofBRCA1 andBRCA2. Compared to the UK population frequencies, we estimated the Danish population frequencies of pathogenic alleles to be higher forBRCA1 (0.0015; 95% CI 0.00064 –0.0034) and lower forBRCA2 (0.00052; 95% CI 0.000...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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AbstractIn the present study, a novel series of quinazoline derivatives is developed for cancer therapy. All the synthesised analogues were evaluated against a panel of 60 human cancer cell lines for the antiproliferative activity. Significant and selective growth inhibition of several solid tumour cell lines such as NCI-H322M, NCI-H522 (non-small cell lung cancer), IGROV1, SK-OV-3 (ovarian cancer), TK-10 (renal cancer) and MDA-MB-468 (breast cancer) was observed. Further, all the new amide analogues strongly inhibited EGFR in low nanomolar range with morpholino quinazoline10 producing activity (IC50 = 6.12&t...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research
Background: The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated.Methods: This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy e...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Cancer treatments can be damaging to the ovary, with implications for future fertility and reproductive lifespan. There is therefore a need for a biomarker than can usefully provide an assessment of the ovary and its potential for long-term function after cancer treatment, and ideally also be of value pre-treatment, for the prediction of post-treatment function. In this review we assess the value of anti-Müllerian hormone (AMH) in this context. Measurement of AMH at the time of cancer diagnosis has been shown to be predictive of whether or not there will remain some ovarian function post-treatment in women with breast...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
The objective of this study was to provide evidence that may help in the classification of these germline variants in terms of their clinical impact and association with the disease in question. A total of 52 unrelated women at-risk for HBOC and negative for BRCA1/BRCA2 pathogenic variants were evaluated through a gene panel comprising 14 breast and/or ovarian cancer susceptibility genes. Of the 453 germline variants identified, 15 variants (classes 3, 4, and 5) in the ATM, BRIP1, CHEK2, MRE11A, MUTHY, PALB2, RAD50, and RAD51C genes were evaluated via databases, co-segregation studies and loss of heterozygosity in the tumo...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Introduction: Carriers of the BRCA 1 and/or BRCA 2 mutation incur a lifetime risk of up to 85% for breast cancer and between 20 and 40% for ovarian cancer. Efforts to elucidate the lifetime risk of developing colorectal cancer with BRCA carrier mutations have demonstrated conflicting results. Consequently, there are no formal guidelines regarding the necessity for bowel screening for individuals with BRCA 1 and/or BRCA 2 mutations. A systematic review and meta-analysis was performed to determine the risk of colorectal cancer associated with BRCA carrier mutations.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: POSTERS A: Genetics Source Type: research
Background: Aromatase inhibitor (AI) is thought to be used with caution, when amenorrhea is induced in chemotherapy. But ovarian function recovery (OFR) is also observed in switching from tamoxifen to AI without chemotherapy. Considering the effect of AI, the identical caution is required. This retrospective study assesses the patients-related and therapy-related factors associated with OFR.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: POSTERS A: Systemic Treatment Source Type: research
The objective of this study is to estimate the risk of new cancer events, (metachronous contralateral breast cancer (CBC) and ovarian cancer (OC)) in BRCA1 mutation carriers with primary breast cancer in population of Latvia, dominated by two founder mutation types. Secondary goal is to verify the risk reduction associated with contralateral prophylactic mastectomy (CPM) and bilateral prophylactic salpingo-ophorectomy (BPSO) procedures.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: POSTERS A: Local Regional Treatment – Surgery Source Type: research
Abstract The Eph (erythropoietin-producing human hepatocellular) receptors form the largest known subfamily of receptor tyrosine kinases. These receptors interact with membrane-bound ephrin ligands via direct cell-cell interactions resulting in bi-directional activation of signal pathways. Importantly, the Eph receptors play critical roles in embryonic tissue organization and homeostasis, and in the maintenance of adult processes such as long-term potentiation, angiogenesis, and stem cell differentiation. The Eph receptors also display properties of both tumor promoters and suppressors depending on the cellular co...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
ConclusionsWomen revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women withBRCA1 orBRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical.
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Our findings contribute to the characterization of the genetic background of breast cancer predisposition in the Brazilian population as a useful resource to discriminate between deleterious variants and VUS, thus enabling improvement in the preventive health care and clinical management of carriers. PMID: 32986223 [PubMed - as supplied by publisher]
Source: Breast Cancer - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
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