title: Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations.
abstract: The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of "other cancers" in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1-6.0) and stomach at 2.4 (95% CI 1.2-4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9-7.8) and prostate (RR 6.3, 95% CI 4.3-9.0) and uveal melanoma (RR 99.4, 95% CI 11.1-359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9-7.8) and stomach (RR 2.7, 95% CI 1.3-4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.
authors.affiliation: North West Cancer Intelligence Service, The Christie NHS Foundation Trust, Manchester, M20 3LJ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Moran
authors.forename: C
authors.initials: C
authors.lastname: O'Hara
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: L
authors.initials: L
authors.lastname: Shack
authors.forename: E
authors.initials: E
authors.lastname: Woodward
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
authors.forename: F
authors.initials: F
authors.lastname: Lalloo
authors.forename: D G R
authors.initials: DG
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics; D012307:Risk Factors; D014604:Uveal Neoplasms / Q000235:genetics; D055815:Young Adult; D000098943:Uveal Melanoma
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human