ISPO

The effect of hormonal and demographic factors on clinical presentation of BRCA1/2 carriers

L Kadouri a, B Uzieli a, A Hubert a, M Gibs a, T Hamburger a, Z Gueta a, I Lerer b, N Weinberg b, P Ever-Hadani c, D Abeliovich b and T Peretz a

a) Sharett Institute of Oncology, b Human Genetic Laboratory and c Department of Biostatistics, Hadassah Medical Center, Jerusalem, Israel).

Aims: The variation in penetrance and clinical presentation of BRCA1/2 mutation carriers suggests a modifying effect of environmental, hormonal and genetic factors. In the present study we evaluated the potential effect of hormonal and demographic factors on clinical presentation of BRCA1/2 carriers. Methods: Study population included 147 patients aged >35 years (114 breast cancer (BC) and 33 ovarian cancer (OC) as first site of diagnosis). All were carriers of one of the 3 Ashkenazi BRCA1/2 mutations. We recorded the year and place of birth (Israel or Eastern Europe/America), age at diagnosis, oral contraceptive use, number of pregnancies, deliveries and children, age at menarche and first pregnancy. For each variable, BC and OC patients were compared in a univariate analysis controlling for age at onset. Significant variables of the univariate analysis, age at diagnosis and year of birth, were introduced into logistic regression analysis with cancer site as a dependant variable. Results: In the univariate analysis, age at menarche and place of birth were the only significant factors affecting clinical presentation. Age at menarche was 13.2 and 12.7 for BC and OC respectively (p=0.03). 57% and 21% of BC and OC respectively were born in Israel (p=0.02). In the logistic regression analysis, age at diagnosis and place of birth were significantly associated with cancer diagnosis (p=0.01, 0.02 respectively). Age at menarche had borderline significance (p=0.08). Conclusion: Hormonal factors seem to play a marginal role in the clinical presentation of BRCA1/2 carriers. The elevated risk for BC in Israeli born women suggests an important role of unknown environmental factors.

For more information, contact tamary@hadassah.org.il

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Familial and Hereditary Cancer.

http://www.cancerprev.org/Journal/Issues/26/101/1192/4389