HEREDITARY BREAST AND OVARIANCANCER SYNDROME

  • In the year 2018 in the United States:
    • Approximately 22 000 women received a new diagnosis of ovarian cancer, and there were 14 000 ovarian cancer deaths
  • Inherited germline mutations:
    • That increase the risk for ovarian cancer:
      • Are present in approximately 7% to 25% of these women
  • Hereditary breast and ovarian cancer syndrome (HBOC):
    • Is the most common genetic syndrome:
      • Linked to ovarian cancer:
        • Is associated with mutations in the BRCA genes
    • BRCA1 and BRCA2 are:
      • Tumor suppressor genes:
        • Involved in the repair of double‐stranded DNA breaks
    • Certain populations are at significantly higher risk for BRCA mutations than the general population including:
      • Ashkenazi Jewish, French Canadian, and Icelandic populations:
        • This is because of the founder effect:
          • Which causes a decrease in genetic diversity in a population that is geographically or reproductively isolated 
          • For example, in the general United States non‐Jewish population:
            • The risk of inheriting a BRCA mutation is 1 in 400 compared with theAshkenazi Jewish population, who carry an increased risk of 1 in 40
    • The inheritance pattern of the BRCA mutations is:
      • Autosomal dominant:
        • However, tumor suppressor genes are known to be recessive, requiring both copies of the gene to be affected
        • Therefore, a germline BRCA mutation is inherited in one copy of the gene, the second copy then undergoes a somatic mutation:
          • The second hit and the carrier is phenotypically affected
  • The most recently estimated cumulative cancer risk by age 80 for:
    • BRCA1 carriers is:
      • 72% 
    • BRCA2 carriers is:
      • 69%
  • By comparison, the lifetime risk of ovarian and breast cancer in the general population is:
    • 1.3% and 12.4%, respectively
  • Furthermore, the lifetime risk for ovarian cancer in:
    • BRCA1 carriers is:
      • 44%
    • BRCA2 carriers is:
      • 17%
  • BRCA carriers are also at risk for other cancers including:
    • Pancreatic, prostate, melanoma, and colon cancer
  • Recently, findings by Shu et al8 suggest that BRCA1 carriers:
    • Have an increased risk for uterine papillary serous carcinoma:
      • rare but aggressive type of uterine cancer
      • In a prospective cohort of 627 BRCA1 carriers:
        • Four women developed serious uterine cancer:
          • Which was double the expected incidence in the general population
  • References:
    • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7‐34. 
    • Noone AM, Howlader N, Krapcho M, et al. “SEER Cancer Statistics Review, 1975‐2015,” National Cancer Institute, Bethesda, MD, 2018. 
    • Morgan RD, Burghel GJ, Flaum N, et al Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases. J Med Genet. 2019;56:301‐307. 
    • McClainMR,PalomakiGE,NathansonKL,etalAdjustingtheestimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: public health implications. Genet Med. 2005;7(1):28‐33. 
    • Gudmundsson J, Johannesdottir G, Bergthorsson JT, et al Different tumor types from BRCA2 carriers show wild‐type chromosome deletions on 13q12‐q13. Cancer Res. 1995;55(21):4830‐4832. 
    • Kuchenbaecker KB, Hopper JL, Barnes DR, et al Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402‐2416. 
    • Mersch J, Jackson MA, Park M, et al Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121(2):269‐275. 

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #HereditaryBreastCancer #BRCA #CASO #CenterforAdvancedSurigcalOncology #Miami

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