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

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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.

Details

Authors
  • 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 Palli
  • And 25 others
  • Franco 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
  • Göran 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine
Original languageEnglish
Pages (from-to)755-767
JournalEndocrine-Related Cancer
Volume14
Issue number3
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes