title: Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: the EPIC study.
abstract: Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, P(trend)  = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, P(trend)  = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, P(trend)  = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Susen
authors.initials: S
authors.lastname: Becker
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chabbert-Buffet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Birgit
authors.initials: B
authors.lastname: Teucher
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Benetou
authors.forename: Elisavet
authors.initials: E
authors.lastname: Valanou
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Rocco
authors.initials: R
authors.lastname: Galasso
authors.forename: Maria-Luísa
authors.initials: ML
authors.lastname: Redondo
authors.forename: Catalina Bonet
authors.initials: CB
authors.lastname: Bonet
authors.forename: Esther
authors.initials: E
authors.lastname: Molina-Montes
authors.forename: Jone M
authors.initials: JM
authors.lastname: Altzibar
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Fränzel J B
authors.initials: FJ
authors.lastname: van Duijnhoven
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.forename: Annika
authors.initials: A
authors.lastname: Idahl
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wareham
authors.forename: Naomi
authors.initials: N
authors.lastname: Allen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Dora
authors.initials: D
authors.lastname: Romaguera
authors.forename: Teresa
authors.initials: T
authors.lastname: Norat
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha