Age at onset of ovarian cancer in women with a strong family history of ovarian cancer

Objective. To determine whether women with a strong family history of ovarian cancer develop ovarian cancer at a younger age than the general population, and to determine if the age at onset of ovarian cancer in families with multiple cases of ovarian cancer is progressively younger with successive generations. Methods. Using a large voluntary familial ovarian cancer registry, 90 probands were identified whose grandmothers had developed ovarian cancer and for whom the age at onset was known. The distribution of age at onset of ovarian cancer in the grandmothers was compared to the expected distribution based on data from the Surveillance Epidemiology End Results (SEER) project. In addition, 131 families were identified for whom complete pedigrees were available and in whom 3 or more family members had developed ovarian cancer. Ovarian cancer-free survival curves were constructed for each aggregate generation (using the probands as the reference generation) utilizing the Kaplan-Meier method. Results. Among the 90 grandmothers, 18 from families with 3 or more cases of ovarian cancer had a distribution of age of onset that was younger than expected (P = 0.02). However, the distribution of age at onset among the 72 grandmothers from families with only 2 cases of ovarian cancer was not significantly different from that expected based on the SEER data (P = 0.18). Among the 131 families with 3 or more cases of ovarian cancer, the probands' daughters developed ovarian cancer at a younger age than the probands (P = 0.018), probands developed ovarian cancer at a younger age than their mothers (P = 0.0008), and the probands' mothers developed ovarian cancer at a younger age than the probands' grandmothers (P = 0.0038). Conclusions. Ovarian cancer patients from families with 3 or more cases of ovarian cancer tend to develop their cancer at a younger than expected age. This is consistent with the phenomenon known as anticipation. (C) 1997 Academic Press.