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An epidemiological model for prediction of endometrial cancer risk in Europe

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Abstract

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30–65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation.

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Acknowledgments

The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue contre le Cancer, Mutuelle Générale de l’Éducation Nationale, Institut National de la Santé et de la Recherche Médicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Norwegian Research Council, Norwegian Cancer Society, ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), The Spanish Ministry of Health (ISCIII RETICC RD06/0020/0091) and the Catalan Institute of Oncology, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no 6236) and Navarra, ISCIII RETIC (RD06/0020; Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).

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The authors have declared no conflicts of interest.

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Correspondence to Anika Hüsing.

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Appendix

Appendix

The relative risk score as part of our model can be derived from the parameter estimates of the relative risk estimates (log(RR)) presented in Table 2 with the following formula: RR = exp [0.030 × BMI − 0.023 × (age at 1st period − 13) − 0.019 (if lean OC-user) − 0.013 (if overweight OC-user) − 0.036 (if obese OC-user) − 0.023 × duration of OC-use (in years) − 0.051 (if single parous) − 0.10 (if 2 full-term pregnancies) − 0.22 (if 3 or more full-term pregnancies) − 0.017 × (age at 1st full-term pregnancy − 24) − 0.088 (if perimeno-pausal) − 0.20 (if postmenopausal) + 0.029 × (age at menopause − 50) + 0.031 × duration of HRT-use (in years) − 0.11 (if premenopausal former smoker) + 0.040 (if premenopausal current smoker) − 0.12 (if postmenopausal former smoker) − 0.21 (if postmenopausal current smoker) − 0.14 (if perimenopausal former smoker)].

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Hüsing, A., Dossus, L., Ferrari, P. et al. An epidemiological model for prediction of endometrial cancer risk in Europe. Eur J Epidemiol 31, 51–60 (2016). https://doi.org/10.1007/s10654-015-0030-9

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