Genome-wide studies of patients carrying pathogenic variants (mutations) in BRCA1 or BRCA2 have reported strong associations between single-nucleotide polymorphisms (SNPs) and cancer risk.
Humans with inherited heterozygous BRCA2 mutations have an increased risk of developing cancer; however, what triggers carcinogenesis in these individuals is unclear.Tan et al. find that environmental and metabolic aldehydes pose a threat to these individuals by promoting degradation of wild-type BRCA2 protein, thereby predisposing them to genomic instability and perhaps to cancer.
The objective of this work was to quantify the contribution of the founder mutations BRCA2c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue.
First, the impact of highly penetrant but lowly prevalent mutations of germline DNA on cancer prognosis has been studied extensively for BRCA1 and BRCA2 mutations as well as mutations related to hereditary nonpolyposis colorectal cancer syndrome.
The aim of the study is to establish the prevalence of BRCAs mutations in SBC to ponder its relevance in the programs of genetic counseling in cancer and to explore the genotype-phenotype relationship of these particular breast cancers.The study was performed in 495 SBC.
Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers.
Suppression of BRCA2 expression by siRNA or shRNA increased the sensitivity to 6-TG- and olaparib-induced apoptosis but did not affect cancer cell response to taxane.
In addition, results from radiation-induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history.
While hundreds of BRCA2-truncating mutations have been associated with an increased cancer risk in carriers, the contribution of unclassified variants (UCVs) to cancer risk remains largely undefined.
Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer.
Twenty-two patients with sporadic cancer and BRCA1 (n = 4) or BRCA2 (n = 18) germline mutations and 105 wild-type patients were identified for this case-control study.
Thus, in Western countries, the mutation status of BRCA1 and BRCA2 is recognized to have an important value with which to assess cancer risk and therapeutic response.
Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC).
In conclusion, the high prevalence of AI at BRCA1 in BRCA2 mutation tumours and vice versa suggests that somatic events occurring at the other breast cancer susceptibility gene locus may be selected in the cancer development.
Since the cancer-predisposing mutation Y42C in BRCA2 significantly compromised the interaction between RPA and BRCA2, this interaction may be biologically important.
Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 or components of the Fanconi anemia (FA) complex incite genomic instability and predispose to malignancy.
Perceived personal risk for cancer and causal attributions for cancer were measured in four groups: women identified as carriers of mutations in breast/ovarian cancer genes BRCA1 BRCA2, habitual smokers, X-ray technicians, and an average-risk group.
Participants with familial pancreatic cancer (FPC) (n = 131) endorsed higher risk perception of pancreatic cancer than the BRCA2 carriers (n = 67) (perceived lifetime risk 42 vs. 15%), but did not differ on cancer worry or general distress prior to the first study appointment.