title: Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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), P(trend) = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99-2.90), P(trend) = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 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.
authors.affiliation: Nutrition and Hormones Unit, International Agency for Research on Cancer, Lyon, France. annec@health.usyd.edu.au
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authors.forename: Dimitrios
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authors.lastname: Trichopoulos
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authors.lastname: Panico
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authors.forename: J R
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authors.lastname: Quirós
authors.forename: Noémie
authors.initials: N
authors.lastname: Travier
authors.forename: Carmen
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authors.lastname: Martínez-García
authors.forename: Nerea
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authors.lastname: Larrañaga
authors.forename: María-Dolores
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authors.lastname: Chirlaque
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authors.lastname: Ardanaz
authors.forename: Göran
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authors.lastname: Berglund
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authors.forename: Fränzel J B
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authors.lastname: van Duijnhoven
authors.forename: Petra H M
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authors.lastname: Peeters
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authors.lastname: Bingham
authors.forename: Kay-Tee
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authors.lastname: Khaw
authors.forename: Naomi
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authors.lastname: Allen
authors.forename: Tim
authors.initials: T
authors.lastname: Key
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Sabina
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authors.lastname: Rinaldi
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mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000209:etiology*; D000328:Adult; D001786:Blood Glucose / Q000502:physiology*; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood / Q000209:etiology*; D005060:Europe; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D009747:Nutritional Physiological Phenomena; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D008055:Lipids; D008074:Lipoproteins