Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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.
Cust
Anne E
AE
Nutrition and Hormones Unit, International Agency for Research on Cancer, Lyon, France. annec@health.usyd.edu.au
Kaaks
Rudolf
R
Friedenreich
Christine
C
Bonnet
Fabrice
F
Laville
Martine
M
Tjønneland
Anne
A
Olsen
Anja
A
Overvad
Kim
K
Jakobsen
Marianne Uhre
MU
Chajès
Véronique
V
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Linseisen
Jakob
J
Lukanova
Annekatrin
A
Boeing
Heiner
H
Pischon
Tobias
T
Trichopoulou
Antonia
A
Christina
Bamia
B
Trichopoulos
Dimitrios
D
Palli
Domenico
D
Berrino
Franco
F
Panico
Salvatore
S
Tumino
Rosario
R
Sacerdote
Carlotta
C
Gram
Inger Torhild
IT
Lund
Eiliv
E
Quirós
J R
JR
Travier
Noémie
N
Martínez-García
Carmen
C
Larrañaga
Nerea
N
Chirlaque
María-Dolores
MD
Ardanaz
Eva
E
Berglund
Göran
G
Lundin
Eva
E
Bueno-de-Mesquita
H Bas
HB
van Duijnhoven
Fränzel J B
FJ
Peeters
Petra H M
PH
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Allen
Naomi
N
Key
Tim
T
Ferrari
Pietro
P
Rinaldi
Sabina
S
Slimani
Nadia
N
Riboli
Elio
E
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
D001786:Blood Glucose; D008055:Lipids; D008074:Lipoproteins