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Ovarian cancer among 8005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2
  1. Sarah Louise Ingham1,2,3,
  2. Jane Warwick4,
  3. Iain Buchan1,
  4. Sarah Sahin3,
  5. Catherine O'Hara5,
  6. Anthony Moran5,
  7. Anthony Howell3,6,
  8. D Gareth Evans2,3
  1. 1Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UK
  2. 2Department of Genetic Medicine, The University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, Central Manchester Hospitals Foundation Trust, Manchester, UK
  3. 3Genesis Prevention Centre, University Hospital of South Manchester, Manchester, UK
  4. 4Imperial Clinical Trials Unit, Faculty of Medicine, School of Public Health, Imperial College London, London, UK
  5. 5NWCIS, The Palatine Centre, Christie Hospital, Manchester, UK
  6. 6Department of Medical Oncology Manchester, Christie Hospital, Manchester, UK
  1. Correspondence to Professor D Gareth Evans, Department of Genetic Medicine, The University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK; gareth.evans{at}cmft.nhs.uk

Abstract

Background Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.

Patients and Methods A prospective study involving women seen at a single family history clinic in Manchester, UK. Patients were excluded if they had ovarian cancer or oophorectomy prior to clinic. Follow-up was censored at the latest date of: 31/12/2010; ovarian cancer diagnosis; oophorectomy; or death. We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.

Results We studied 8005 women from 895 families. Women from BRCA2 mutation families showed a 17-fold increased risk of invasive ovarian cancer (relative risk (RR) 16.67; 95% CI 5.41 to 38.89). This risk increased to 50-fold in women from families with BRCA1 mutations (RR 50.00; 95% CI 26.62 to 85.50). No association was found for women in families tested negative for BRCA1/2, where there was 1 observed invasive ovarian cancer in 1613 women when 2.74 were expected (RR 0.37; 95% CI 0.01 to 2.03). There was no association with ovarian cancer in families untested for BRCA1/2 (RR 0.99; 95% CI 0.45 to 1.88).

Discussion This study showed no increased risk of ovarian cancer in families that tested negative for BRCA1/2 or were untested. These data help counselling women from BRCA1/2 negative families with breast cancer that their risk of invasive ovarian cancer is not higher than the general population.

  • Cancer: ovarian
  • Cancer: breast
  • BRCA

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