GTS5:BRCA-related cancer predisposition syndrome (BRCA1, BRCA2): Difference between revisions
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==Epidemiology/Prevalence== | ==Epidemiology/Prevalence== | ||
=== ''BRCA1'' === | |||
* '''Incidence / Carrier frequency:''' Germline pathogenic variants in ''BRCA1'' occur in approximately 1 in 400–500 individuals in the general population, with higher prevalence in certain founder populations (e.g., ~1 in 40 in Ashkenazi Jewish individuals). | |||
* '''Cancer risk''' (heterozygous carriers): Heterozygous pathogenic variants in ''BRCA1'' are associated with a high lifetime risk of breast and ovarian cancer, with incomplete penetrance and variable expressivity. | |||
* '''Lifetime cancer risks:''' | |||
** Female breast cancer: ~60–80% lifetime risk (relative risk ~7–10 fold compared with the general population) | |||
** Ovarian cancer: ~35–45% lifetime risk | |||
** Male breast cancer: Increased risk, though substantially lower than in females | |||
** Other cancers: Increased risk of prostate and pancreatic cancers | |||
* '''Tumor characteristics:''' ''BRCA1'' associated breast cancers are enriched for triple negative breast cancer (TNBC) and frequently display a homologous recombination deficient (HRD) phenotype. | |||
=== ''BRCA2'' === | |||
* '''Incidence / Carrier frequency:''' Germline pathogenic variants in ''BRCA2'' are present in approximately 1 in 400–500 individuals in the general population, with increased prevalence in founder populations (e.g., Ashkenazi Jewish). | |||
* '''Cancer risk (heterozygous carriers):''' Heterozygous pathogenic variants in ''BRCA2'' confer substantially increased risks for breast, ovarian, pancreatic, prostate, and male breast cancers, with incomplete penetrance. | |||
* '''Lifetime cancer risks:''' | |||
** Female breast cancer: ~45–70% lifetime risk (relative risk ~5–7-fold) | |||
** Ovarian cancer: ~10–30% lifetime risk | |||
** Male breast cancer: Significantly increased compared with the general population | |||
** Prostate cancer: Elevated risk, often with earlier onset and aggressive features | |||
** Pancreatic cancer: Moderately increased risk | |||
* '''Tumor characteristics:''' ''BRCA2'' associated breast cancers are more often hormone receptor positive, though HRD remains a defining molecular feature. | |||
==Genetic Abnormalities: Germline== | ==Genetic Abnormalities: Germline== | ||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span> | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span> | ||