Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 129, Issue 8, Pages 2032-2037Publisher
WILEY
DOI: 10.1002/ijc.25840
Keywords
tumor necrosis factor (TNF)-alpha; soluble TNF receptors; inflammation; endometrial cancer; prospective
Categories
Funding
- World Cancer Research Fund [2007/13]
- ISCIII (Spanish Ministry of Health and the participating regional governments and institutions of Spain) [RETICC DR06/0020]
- European Commission (SANCO)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Institut Gustave Roussy
- Ligue contre le Cancer
- Mutuelle Generale de l'Education Nationale (France)
- German Cancer Aid
- German Cancer Research Centre
- German Federal Ministry of Education and Research (Germany)
- Danish Cancer Society
- Cancer Research UK
- Medical Research Council, UK
- Hellenic Ministry of Health
- Stavros Niarchos Foundation
- Hellenic Health Foundation
- Italian Association for Research on Cancer
- Italian National Research Council
- Dutch Ministry of Public Health
- Welfare and Sports, Dutch Ministry of Public Health
- Welfare and Sports (VWS)
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF) (The Netherlands)
- Statistics Netherlands, Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane, Sweden
- Norwegian Cancer Society
- Medical Research Council [MC_U106179471, G1000143, G0401527] Funding Source: researchfish
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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.
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