title: Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers.
abstract: OBJECTIVE
  Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction.
  
  
  METHODS
  Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status.
  
  
  RESULTS
  Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups.
  
  
  CONCLUSIONS
  Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6021, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Finkelman
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Rubinstein
authors.forename: Sue
authors.initials: S
authors.lastname: Friedman
authors.forename: Tara M
authors.initials: TM
authors.lastname: Friebel
authors.forename: Shera
authors.initials: S
authors.lastname: Dubitsky
authors.forename: Niecee Singer
authors.initials: NS
authors.lastname: Schonberger
authors.forename: Rochelle
authors.initials: R
authors.lastname: Shoretz
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weitzel
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Carrie
authors.initials: C
authors.lastname: Snyder
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Pichert
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Laura
authors.initials: L
authors.lastname: van't Veer
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bancroft
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Gail E
authors.initials: GE
authors.lastname: Tomlinson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Ellen
authors.initials: E
authors.lastname: Matloff
authors.forename: Susan
authors.initials: S
authors.lastname: Domchek
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007585:Jews / Q000235:genetics* / Q000706:statistics & numerical data; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D040242:Risk Reduction Behavior