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Case–control study of inflammatory markers and the risk of endometrial cancer

Friedenreich, Christine M.a,b,c; Langley, Annie R.a; Speidel, Thomas P.a; Lau, David C.W.d,e; Courneya, Kerry S.f; Csizmadi, Ilonaa,b,c; Magliocco, Anthony M.h; Yasui, Yutakag; Cook, Linda S.a,b,i

European Journal of Cancer Prevention: July 2013 - Volume 22 - Issue 4 - p 374–379
doi: 10.1097/CEJ.0b013e32835b3813
Research Papers: Gynecological Cancer

Chronic inflammation may be important in endometrial cancer etiology. Several established endometrial cancer risk factors, particularly obesity, are hypothesized to operate through this pathway by increasing proinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and acute-phase protein C-reactive protein (CRP). This study sought to investigate the association between inflammatory markers and the risk of endometrial cancer (types I and II). We recruited 519 incident endometrial cancer cases and 964 frequency age-matched controls in this population-based case–control study in Alberta (Canada) from 2002 to 2006. Participants completed in-person interviews, were assessed for anthropometric measures, and provided 8-h fasting blood samples either preoperatively or postoperatively. Blood was analyzed for the concentrations of TNF-α, IL-6, and CRP by immunoassay. Endometrial cancer cases had consistently higher mean levels of TNF-α, IL-6, and CRP compared with controls in these predominantly postmenopausal women. After adjusting for age, all markers were associated with statistically significant increased risks for endometrial cancer; however, after multivariable adjustment, only the risk from CRP remained elevated (odds ratio=1.22, 95% confidence interval: 1.02–1.47). Similarly, upon stratification by cancer type, only CRP was associated positively with an increased risk for type I endometrial cancer (odds ratio=1.25, 95% confidence interval: 1.03–1.52). All markers were associated with an elevated risk for the more rare and aggressive type II cancers; however, these findings were statistically nonsignificant, likely because of the small number of cases in this group. In conclusion, we found epidemiologic evidence for an association between CRP and the risk of endometrial cancer, which was slightly stronger for type I cancer. No associations emerged for TNF-α and IL-6.

aDepartment of Population Health Research, Division of Cancer Care, Alberta Health Services

Departments of bCommunity Health Sciences

cOncology

dMedicine

eBiochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, Calgary

fFaculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta

gSchool of Public Health, University of Alberta, Edmonton, Alberta, Canada

hDepartment of Anatomical Pathology, H. Lee Moffitt Cancer Centre, Tampa, Florida

iDepartment of Internal Medicine, NM Health Sciences Center, University of New Mexico, Albuquerque, New Mexico, USA

Correspondence to Christine M. Friedenreich, PhD, Department of Population Health Research, Division of Cancer Care, Alberta Health Services, Box ACB, 2210-2nd St SW, Calgary, Alberta, Canada T2S 3C3 Tel: +1 403 698 8009; fax: +1 403 476 2654; e-mail: christine.friedenreich@albertahealthservices.ca

Received May 29, 2012

Accepted September 9, 2012

© 2013 Lippincott Williams & Wilkins, Inc.