Penetrances of BRCA1 1675delA and 1135insA with respect to breast cancer and ovarian cancer

For genetic counseling and predictive testing in families with inherited br east-ovarian cancer, penetrances and expressions of the underlying mutation s should be known. We have previously reported two BRCA1 founder mutations in the Norwegian population. Index cases for the present study were found t wo different ways: through a series of consecutive ovarian cancers (n = 16) and through our family cancer clinic (n = 14). Altogether, 20 of the patie nts had BRCA1 1675delA, and 10 had 1135insA. Their relatives were described with respect to absence/presence of breast and/or ovarian cancer. Of 133 l iving female relatives, 83 (62%) were tested for the presence of a mutation . No difference, in penetrance and expression, between the two mutations we re found, whereas differences according to method of ascertainment were see n. The overall findings were that disease started to occur at age 30 years and that by age 50 years 48% of the mutation-carrying women had experienced breast and/or ovarian cancer. More ovarian cancers than breast cancers wer e recorded. Both penetrance and expression (breast cancer vs. ovarian cance r) were different from those in reports of the Ashkenazi founder mutations. Whether the reported differences reflect true differences and/or methodolo gical problems is discussed. An observed excess of mutation carriers could not be accounted for by methodological problems; possible explanations were a "true" low penetrance or preferential segregation.