title: The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.
abstract: BACKGROUND
  Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer. Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area.
  
  
  METHODS
  We collected blood samples from 5318 Jewish subjects who had filled out epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the polymerase chain reaction. We estimated the risks of breast and other cancers by comparing the cancer histories of relatives of carriers of the mutations and noncarriers.
  
  
  RESULTS
  One hundred twenty carriers of a BRCA1 or BRCA2 mutation were identified. By the age of 70, the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent). There were no significant differences in the risk of breast cancer between carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of colon cancer among the relatives of carriers was not elevated.
  
  
  CONCLUSIONS
  Over 2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer increased risks of breast, ovarian, and prostate cancer. The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7372, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Struewing
authors.forename: P
authors.initials: P
authors.lastname: Hartge
authors.forename: S
authors.initials: S
authors.lastname: Wacholder
authors.forename: S M
authors.initials: SM
authors.lastname: Baker
authors.forename: M
authors.initials: M
authors.lastname: Berlin
authors.forename: M
authors.initials: M
authors.lastname: McAdams
authors.forename: M M
authors.initials: MM
authors.lastname: Timmerman
authors.forename: L C
authors.initials: LC
authors.lastname: Brody
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics; D003110:Colonic Neoplasms / Q000208:ethnology / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007585:Jews; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors