Risk Factors for Epithelial Borderline Ovarian Tumors: Results of a Swedish Case–Control Study Tomas Riman, M.D.,* , ² , ‡ ,1 Paul W. Dickman, Ph.D.,² Staffan Nilsson, M.D., Ph.D.,* , ‡ Nestor Correia, Ph.D.,² Hans Nordlinder, M.D., Ph.D.,§ ,¶ Cecilia M. Magnusson, M.D., Ph.D.,² and Ingemar R. Persson, M.D., Ph.D.² *Department of Obstetrics and Gynecology, Falu Hospital, 79182 Falun, Sweden; ² Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden; ‡Department of Obstetrics and Gynecology, and §Department of Pathology, Uppsala University, Uppsala, Sweden; and ¶ Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden Received May 2, 2001 Objective. Borderline ovarian tumors have a favorable progno- sis. Previous epidemiological studies indicate common risk factors forinvasive epithelial ovarian cancers and borderline tumors, but it remains unresolved whether these tumors are precursors of invasive cancers ora separate disease entity. The objective of this population-based case–control study conducted in 1993–1995 was to examine reproductive and otherfactors in relation to the risk of borderline ovarian tumors. Methods. Subjects were 193 histologically verified incident epi- thelial borderline tumor cases and 3899 randomly selected controls aged 50–74 years, whose data were collected through mailed questionnaires. Risk estimates were calculated by unconditional logistic regression. Results. Ever parous women were at reduced risk, with odds ratios of 0.44 (95% confidence interval (CI) 0.26–0.75) for serous and 0.63 (95%CI 0.34 –1.19) for mucinous tumors. No clear trends emerged for age at first birth, at menarche, and at menopause. Lactation reduced tumor risk. Oral contraceptive ever use con- ferred no protection, with odds ratios of 1.40 (95%CI 0.87–2.26) for serous and 1.04 (95%CI 0.61–1.79) for mucinous tumors. The odds ratio for serous tumors following unopposed estrogen ever use was 2.07 (95% CI 1.08–3.95), whereas no risk increase ap- peared with estrogens supplemented by cyclic or continuous pro- gestins. Mucinous tumors were not associated with hormone re- placement therapy. The odds ratio for serous tumors in the highest category of body mass index was 6.47 (95% CI 3.09–13.5). Conclusions. Increasing parity and lactation reduce the risk of borderline ovarian tumors in women aged 50–74, while no pro- tection follows oral contraceptive use. Hormonal situations such as unopposed estrogen use and obesity, where estrogens are not counteracted by progestins, may increase the risk of serous tumors. © 2001 Academic Press Key Words: case–control studies; borderline ovarian tumors; epidemiology; risk factors. INTRODUCTION Epithelial ovarian tumors of low malignant potential consti- tute a subgroup of ovarian malignancies and are also called borderline ovarian tumors. These tumors are mostly of serous or mucinous histology, display mitotic and nuclear abnormal- ities, show cellular multilayering, and are capable of metasta- sis, but respect the ovarian stroma [1–3]. Compared to invasive epithelial ovarian cancers, borderline tumors occur in younger women, present at an earlier stage, and have a favorable prognosis [4 –9]. The incidence rate of borderline tumors is lower than that for invasive cancers [10 –11], with proportions of borderline tumors ranging from 12 to 33% in epithelial ovarian tumor series [11]. Most of the published epidemiological data on epithelial ovarian cancer risk consider either invasive cancers or invasive and borderline tumors combined. Increasing parity, lactation, oral contraceptive use, tubal ligation, and hysterectomy seem protective, while a positive family history and infertility may be associated with higher risk [12–15]. Results from the rela- tively few epidemiological studies evaluating borderline tu- mors separately indicate that most of the risk factors for inva- sive cancers also pertain to borderline tumors [14, 16 –19], but it remains unresolved whether borderline tumors are precursors of invasive cancers or a separate disease entity. We have conducted a nationwide case– control study de- signed to investigate the effects of reproductive and some other factors on the risk of epithelial ovarian malignancies of differ- ent histologic subtypes in peri- and postmenopausal women. Here we report how reproductive events, oral contraceptives, hormone replacement therapy (HRT), gynecological surgery, family history, body mass index, and certain lifestyle factors relate to the risk of epithelial borderline ovarian tumors. MATERIALS AND METHODS Women in this population-based case– control study were aged 50 –74, born and resident in Sweden, and recruited from 1 To whom correspondence and reprint requests should be addressed. Fax: 46 23 490989. E-mail: tomas.riman@ltdalarna.se. Gynecologic Oncology 83, 575–585 (2001) doi:10.1006/gyno.2001.6451, available online at http://www.idealibrary.com on 575 0090-8258/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.