Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: the EPIC study.
Dossus L., Becker S., Rinaldi S., Lukanova A., Tjønneland A., Olsen A., Overvad K., Chabbert-Buffet N., Boutron-Ruault M-C., 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 M-L., Bonet CB., Molina-Montes E., Altzibar JM., Chirlaque M-D., Ardanaz E., Bueno-de-Mesquita HB., van Duijnhoven FJB., Peeters PHM., Onland-Moret NC., Lundin E., Idahl A., Khaw K-T., Wareham N., Allen N., Romieu I., Fedirko V., Hainaut P., Romaguera D., Norat T., Riboli E., Kaaks R.
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.