Influence of selected hormonal and lifestyle factors on familial propensity to ovarian cancer Alessandra Tavani, a, * Cristina Bosetti, a Luigino Dal Maso, b Laura Giordano, a Silvia Franceschi, c and Carlo La Vecchia a,d a Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Via Eritrea 62, 20157 Milan, Italy b Centro di Riferimento Oncologico, 33081 Aviano (PN), Italy c International Agency for Research on Cancer, Lyon Cedex, France d Istituto di Statistica Medica e Biometria, Universita ` degli Studi di Milano, 20133 Milan, Italy Received 26 August 2003 Abstract Aim. To study the influence of established risk factors for ovarian cancer in women with a family history of ovarian and/or breast cancer. Methods. Italian hospital-based case-control study. Cases were 1031 women with incident epithelial ovarian cancer and controls were 2411 women. Two ‘‘Adult life risk scores’’ (ALRS) were defined combining the effect of hormonal and lifestyle risk factors. Results. Ovarian cancer risk increased with low number of children, late menopause, never or short oral contraceptive use, physical inactivity, rich red meat intake and low fish, pulse and vegetable intake. For hormonal factors, compared to women without a family history and low ALRS, the odds ratios (OR) was 1.77 for women without family history and high ALRS, 2.51 for women with family history and low ALRS and 5.99 for women with family history and high ALRS. The corresponding values for the lifestyle ALRS were 2.00, 2.24 and 7.43. Conclusions. Intervention on selected hormonal and lifestyle risk factors might be more important for women with family history of ovarian and/or breast cancer. D 2004 Elsevier Inc. All rights reserved. Keywords: Case-control studies; Diet; Family history; Menstrual factors; Oral contraceptives; Ovarian cancer; Reproductive factors; Risk factors Introduction A family history of ovarian and/or breast cancer is a recognised risk factor for ovarian cancer [1,2], and BRCA1 [3] and BRCA2 [4] genes have been related to familial ovarian and breast cancers [5]. Established factors associat- ed with ovarian cancer risk include menstrual and repro- ductive characteristics [6], such as low parity [7–11], never use of oral contraceptives [12,13] and early menopause [14]. The role of other lifestyle factors is less clear, but physical inactivity [15] and red meat intake [16–18] have been suggested as possible risk indicators, while consumption of fish, vegetables and pulses as protective ones [17]. Women with a family history of ovarian and/or breast cancer may inherit genetic changes that alter their risk of ovarian cancer, but the influence of other established risk factors for ovarian cancer in women with a family history of the diseases has not been quantified, and estimates are usually based on a limited number of cases with a family history. Oral contraceptive use may reduce the risk of ovarian cancer in women with pathogenic mutations in the BRCA1 and BRCA2 gene [12]. In an American study, the risk reduction from long-term use of oral contraceptives was greater in women with a positive family history of ovarian cancer than in those with a negative family history [19], and in another American study, nulliparity was more strongly associated with an increased risk of ovarian cancer among women with a family history of breast or ovarian cancer [20]. In Jewish women carriers of mutations in the BRCA1 and BRCA2 gene, the risk of ovarian cancer decreased with each birth, but not with increased duration of use of oral contraceptives [21]. A study, conducted in Italy in the late 1980s, found a substantial increased risk of ovarian cancer in women with both a family history of breast or ovarian cancer and a combination of hormonal risk factors, com- pared with women with similar hormonal risk factors but without a family propensity for the disease [22]. A French 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2003.11.038 * Corresponding author. Fax: +39-02-390-01916. E-mail address: tavani@marionegri.it (A. Tavani). www.elsevier.com/locate/ygyno Gynecologic Oncology 92 (2004) 922 – 926