Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: the EPIC study.
International journal of cancer 2010 ; 129: 2032-7.
Dossus L, Becker S, Rinaldi S, Lukanova A, Tjønneland A, Olsen A, Overvad K, Chabbert-Buffet N, Boutron-Ruault MC, Clavel-Chapelon F, Teucher B, Chang-Claude J, Pischon T, Boeing H, Trichopoulou A, Benetou V, Valanou E, Palli D, Sieri S, Tumino R, Sacerdote C, Galasso R, Redondo ML, Bonet CB, Molina-Montes E, Altzibar JM, Chirlaque MD, Ardanaz E, Bueno-de-Mesquita HB, van Duijnhoven FJ, Peeters PH, Onland-Moret NC, Lundin E, Idahl A, Khaw KT, Wareham NJ, Allen N, Romieu I, Fedirko V, Hainaut P, Romaguera D, Norat T, Riboli E, and Kaaks R
DOI : 10.1002/ijc.25840
PubMed ID : 21154749
PMCID : 0
URL : https://pubmed.ncbi.nlm.nih.gov/21154749/
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.