BCLC-study: Risks to cancers other than those of the breast and ovary conferred by BRCA2

Coordinator Doug Easton (Cambridge, UK) 
Aim To determine the spectrum of cancers other than those of the breast and ovary associated with mutations in BRCA2, and to provide estimates of the relative risks to these cancers.
Calls for Cancer ascertainment data in families with a proven mutation in BRCA2.
Status Data accrual closed; analysis completed; manuscript in press with JNCI


The risks of cancer in BRCA2 mutation carriers have been investigated in 173 families with BRCA2 mutations identified by 20 centres in Europe and North America. Cancer occurrence was determined in a cohort of  962 individuals with breast and/or ovarian cancer, and 3731 individuals who were either known carriers or were first degree relatives of known carriers or of breast or ovarian cancer cases. Incidence rates were compared to population specific incidence rates, and relative risks to carriers estimated by maximum likelihood. Significantly increased risks were observed for prostate cancer (estimated RR 4.65, 95%CI 3.48-6.22), pancreatic cancer (RR  3.51, 95%CI 1.87-6.58), gall bladder cancer (RR 4.97, 95%CI 1.50-16.52), buccal cavity and pharynx cancer (RR 2.26, 95%CI 1.09-4.68), stomach cancer (RR 2.59, 95%CI 1.46-4.61) and malignant melanoma (RR 2.58, 95%CI 1.28-5.17). The relative risk for prostate cancer rose to 7.33 below age 65. Based on the risks of contralateral breast cancer and of ovarian cancer in women affected with breast cancer, the cumulative risks of breast and ovarian cancer by age 70 were estimated to be 52.3% (95%CI 41.1-61.4) and 15.9% (95%CI 8.0-23.1) respectively. The overall cumulative risk of cancer by age 70 was estimated to be 32%  in male carriers and 90% in female carriers.

BCLC - April 1999