Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

About 5%-10% of breast cancer is hereditary with BRCA1 and BRCA2 being the most common genes associated with hereditary breast cancer (HBC). Several additional genes have recently been associated with HBC. These genes can be classified as highly or moderately penetrant genes with lifetime risk >30% or 17%-30%, respectively. Highly penetrant genes associated with HBC include TP53, PTEN, CDH1, STK11, and PALB2. While, moderately penetrant genes include CHEK2, ATM, BARD1, BRIP1, NBN, NF1, RAD51D, and MSH6. Breast cancer risk and recommendations for screening and risk-reduction vary by gene. In general, screening breast MRI is recommended for women at >20% lifetime risk, which includes women with mutations in highly penetrant genes and the majority (but not all) moderately penetrant genes. Consideration of chemoprevention is recommended for women with mutations in high and moderately penetrant genes. Risk-reducing mastectomy does reduce the risk of breast cancer to the greatest extent and can be considered for women with highly penetrant genes. However, this procedure is associated with significant morbidities that should be considered, especially given the benefit of using screening breast MRI for high-risk women. BSO is only recommended for women with mutations in genes associate with increased risk for ovarian cancer and not as a breast cancer risk-reducing strategy. As more women undergo testing, additional genes may be identified and risk estimates for current genes and management recommendations may be modified.
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PMID:Risk for breast cancer and management of unaffected individuals with non-BRCA hereditary breast cancer. 3274 Oct 80

The use of multigene panel testing for patients with a predisposition to breast/ovarian cancer is increasing as the identification of variants is useful for diagnosis and disease management. We identified pathogenic and likely pathogenic (P/LP) variants of high-and moderate-risk genes using a 23-gene germline cancer panel in 518 patients with hereditary breast and ovarian cancers (HBOC). The frequency of P/LP variants was 12.4% (64/518) for high- and moderate-penetrant genes, namely, BRCA2 (5.6%), BRCA1 (3.3%), CHEK2 (1.2%), MUTYH (0.8%), PALB2 (0.8%), MLH1 (0.4%), ATM (0.4%), BRIP1 (0.4%), TP53 (0.2%), and PMS2 (0.2%). Five patients possessed two P/LP variants in BRCA1/2 and other genes. We also compared the results from in silico splicing predictive tools and exon splicing patterns from patient samples by analyzing RT-PCR product sequences in six P/LP intronic variants and two intronic variants of unknown significance (VUS). Altered transcriptional fragments were detected for P/LP intronic variants in BRCA1, BRIP1, CHEK2, PARB2, and PMS2. Notably, we identified an in-frame deletion of the BRCA1 C-terminal (BRCT) domain by exon skipping in BRCA1 c.5152+6T>C-as known VUS-indicating a risk for HBOC. Thus, exon splicing analysis can improve the identification of veiled intronic variants that would aid decision making and determination of hereditary cancer risk.
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PMID:Exon splicing analysis of intronic variants in multigene cancer panel testing for hereditary breast/ovarian cancer. 3276 68

Hereditary breast cancer syndromes affect a small (10-15% of cases) but significant group of patients. BRCA1 and BRCA2 are the most familiar and well-studied genes associated with inherited breast cancer. However, mutations in the high-penetrance genes, TP53, PTEN, CDH1, MSH1, MLH1, MSH6, PMS2, PALB2, and STK11, and in the moderate-penetrance genes, CHEK2, ATM, and BRIP1, also correlate with high lifetime risks of breast cancer and other malignancies as well. Advances in breast cancer genetics have led to an improved perception of diagnosis and screening strategies. The specific considerations and challenges involved in treating this unique population have become a fertile ground for research. Indeed, these genes and downstream molecular pathways have now become potential therapeutic targets in breast cancer patients, including those with BRCA1 or BRCA2 mutations. This review describes the variety of hereditary breast cancer genes, from their molecular origins to the prognosis and multidisciplinary clinical decision-making processes. Key publications and other reported recent clinical trials and guidelines are provided.
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PMID:Comparison of Patient Susceptibility Genes Across Breast Cancer: Implications for Prognosis and Therapeutic Outcomes. 3280 35

In designing national strategies for genetic testing, it is important to define the full spectrum of pathogenic mutations in prostate cancer (PCa) susceptibility genes. To investigate the frequency of mutations in PCa susceptibility genes in Polish familial PCa cases and to estimate gene-related PCa risks and probability of aggressive disease, we analyzed the coding regions of 14 genes by exome sequencing in 390 men with familial prostate cancer and 308 cancer-free controls. We compared the mutation frequencies between PCa cases and controls. We also compared clinical characteristics of prostate cancers between mutation carriers and noncarriers. Of the 390 PCa cases, 76 men (19.5%) carried a mutation in BRCA1, BRCA2, NBN, ATM, CHEK2, HOXB13, MSH2 or MSH6 genes. No mutations were found in BRIP1, PTEN, TP53, MLH1, PMS2 and SPOP. Significant associations with familial PCa risk were observed for CHEK2, NBN, ATM, and HOXB13. High-grade (Gleason 8-10) tumors were seen in 56% of BRCA2, NBN or ATM carriers, compared to 21% of patients who tested negative for mutations in these genes (OR = 4.7, 95% CI 2.0-10.7, P = .0003). In summary, approximately 20% of familial prostate cancer cases in Poland can be attributed to mutations in eight susceptibility genes. Carriers of mutations in BRCA2, NBN and ATM develop aggressive disease and may benefit from intensified screening and/or chemotherapy.
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PMID:Mutations in ATM, NBN and BRCA2 predispose to aggressive prostate cancer in Poland. 3287 59

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20-25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.
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PMID:Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes. 3289 12


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