Tumor necrosis factor (TNF)-alpha, soluble TNF receptors and endometrial cancer risk: the EPIC study

Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-alpha (TNF-alpha), 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-alpha 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-alpha (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-alpha 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.