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.