Author:
Cust Anne E,Kaaks Rudolf,Friedenreich Christine,Bonnet Fabrice,Laville Martine,Tjønneland Anne,Olsen Anja,Overvad Kim,Jakobsen Marianne Uhre,Chajès Véronique,Clavel-Chapelon Françoise,Boutron-Ruault Marie-Christine,Linseisen Jakob,Lukanova Annekatrin,Boeing Heiner,Pischon Tobias,Trichopoulou Antonia,Christina Bamia,Trichopoulos Dimitrios,Palli Domenico,Berrino Franco,Panico Salvatore,Tumino Rosario,Sacerdote Carlotta,Gram Inger Torhild,Lund Eiliv,Quirós J R,Travier Noémie,Martínez-García Carmen,Larrañaga Nerea,Chirlaque María-Dolores,Ardanaz Eva,Berglund Göran,Lundin Eva,Bueno-de-Mesquita H Bas,van Duijnhoven Fränzel J B,Peeters Petra H M,Bingham Sheila,Khaw Kay-Tee,Allen Naomi,Key Tim,Ferrari Pietro,Rinaldi Sabina,Slimani Nadia,Riboli Elio
Abstract
To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38–0.97), Ptrend = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99–2.90), Ptrend = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46–4.66), Ptrend = 0.0006, Pheterogeneity = 0.13) and never-users of exogenous hormones (Pheterogeneity = 0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51–2.97)), which increased with the number of MetS factors (Ptrend = 0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (Pinteraction = 0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
Subject
Cancer Research,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism