Reproduction history and lifestyle factors in BRCA1 and BRCA2 mutation carriers and high risk subjects affected or nonaffected by cancer.

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BACKGROUND: Lifestyle factors and reproductive history are related to risk of breast and ovarian cancer in the general population and in higher risk subjects. We investigated the role of some of these factors in a consecutive series of subjects followed in our High Risk Clinic. METHODS AND RESULTS: 300 affected and healthy subjects were recruited (126 BRCA1/2 positive, 138 wild-type, 36 true negative). 138 had breast, 24 ovarian, 5 ovarian and breast, 37 bilateral breast and 3 other cancers. Median age=43yrs (21-88), median age at menarche=12yrs (9-14), median age at first pregnancy=27yrs (17-30), median BMI=22 (14-24), ever users of oral contraceptives (>6 months)=164. A >4kg increase between current and at 18yrs weight seems to be an important risk factor for cancer (P=0.0043) in carriers (RR=3.42, 95%CI 1.44-8.17). The use of oral contraceptives was associated to a slightly significant increase of number of breast cancers compared to ovarian cancers (with or without breast cancers) in wild-type subjects (P=0.06). The frequency of breast cancer, compared to ovarian cancer, is lower in women with at least one pregnancy (P=0.03), and, considering only wild-type patients, greater in women with age at first pregnancy >27yrs (P=0.08). No significant association between young age at menarche (<12) and malignancy, in carriers and wild-type subjects, was found. CONCLUSIONS: This study suggests an association of body weight changes and pregnancy with cancer in mutation carriers. Oral contraceptives and age at first pregnancy seem to be associated more with breast than ovarian cancers in patients with no mutations.