title: Inverse birth cohort effects in ovarian cancer: Increasing risk in BRCA1/2 mutation carriers and decreasing risk in the general population.
abstract: OBJECTIVE
  BRCA1/2 carriers are at increased risk of ovarian cancer, and some reports suggest an increasing risk in more recent birth cohorts. In contrast, decreasing incidences have been observed in the general population. The aim was to assess the birth cohort effect on ovarian cancer risk in BRCA1/2 carriers relative to their background general population.
  
  
  METHODS
  Data on ovarian cancer incidence was collected for a cohort of 1050 BRCA1/2 mutation carriers ascertained by our regional clinic and retrieved from the general Dutch population cancer registry. Birth cohorts were categorized as pre-1935, 1935-1953, post-1953. Birth cohort effects on the ovarian cancer risk were estimated using hazard ratios (HRs) in BRCA1/2 carriers and Poisson rate ratios in the general population. Standardized incidence ratios (SIRs) were calculated to compare populations. HRs were adjusted for mutation position and family history.
  
  
  RESULTS
  Compared to the pre-1935 cohort, BRCA1 carriers in the 1935-1953 and post-1953 cohorts had an increased ovarian cancer risk of HRadjusted 1.54 (95% CI 1.11-2.14) and 2.40 (95% CI 1.56-3.69), respectively. BRCA2 carriers in the 1935-1953 cohort had an HRadjusted of 3.01 (95% CI 1.47-6.13). The SIRs for the 1935-1953 and post-1953 cohorts were 1.7 and 2.7, respectively, for the BRCA1 carriers and 1.6 times and 2.4 times, respectively, for BRCA2 carriers.
  
  
  CONCLUSIONS
  Mutation carriers, particularly BRCA1 carriers, born in the most recent cohorts, have the highest additional ovarian cancer risk as compared to the general population.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. Electronic address: j.r.vos01@umcg.nl.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Vos
authors.affiliation: Department of Gynaecologic Oncology, University of Groningen, University Medical Centre Groningen, Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Mourits
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Natalia
authors.initials: N
authors.lastname: Teixeira
authors.affiliation: Department of Surgical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Jansen
authors.affiliation: Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Oosterwijk
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
mesh_terms: D000367:Age Factors; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*
keywords: BRCA1 gene; BRCA2 gene; Birth cohort; Ovarian cancer; Risk assessment