Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Anne E. Cust, Rudolf Kaaks, Christine Friedenreich, Fabrice Bonnet, Martine Laville, Anne Tjonneland, Anja Olsen, Kim Overvad, Marianne Uhre Jakobsen, Veronique Chajes, Frangoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Jakob Linseisen, Annekatrin Lukanova, Heiner Boeing, Tobias Pischon, Antonia Trichopoulou, Bamia Christina, Dimitrios Trichopoulos, Domenico PalliFranco Berrino, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Inger Torhild Gram, Eiliv Lund, J. R. Quiros, Nomie Travier, Carmen Martinez Garcia, Nerea Larranaga, Maria-Dolores Chirlaque, Eva Ardanaz, Goran Berglund, Eva Lundin, H. Bas Bueno-De-Mesquita, J. B. van Duijnhoven Franzel, Petra H. M. Peeters, Sheila Bingham, Kay-Tee Khaw, Naomi Allen, Tim Key, Pietro Ferrari, Sabina Rinaldi, Nadia Slimani, Elio Riboli

Research output: Contribution to journalJournal articleResearchpeer-review

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 (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=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 (P-trend=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 (P-interaction=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.
Original languageEnglish
JournalEndocrine - Related Cancer
Volume14
Issue number3
Pages (from-to)755-767
Number of pages13
ISSN1351-0088
DOIs
Publication statusPublished - 2007
Externally publishedYes

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