Christine M Friedenreich1,2,3,4, Jeroen W G Derksen5,6,7, Thomas Speidel8, Darren R Brenner8,9,10, Emily Heer8, Kerry S Courneya11, Linda S Cook10,12. 1. Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, AB, Canada. christine.friedenreich@ahs.ca. 2. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. christine.friedenreich@ahs.ca. 3. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. christine.friedenreich@ahs.ca. 4. Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Holy Cross Centre, Room 514, Box ACB, 2210 2nd Street S.W., Calgary, AB, T2S 3C3, Canada. christine.friedenreich@ahs.ca. 5. Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. 6. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. 7. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. 8. Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, AB, Canada. 9. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 10. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 11. Faculty of Kinesiology, Sport and Recreation, University of Alberta, Edmonton, AB, Canada. 12. Department of Internal Medicine, NM Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Abstract
BACKGROUND: Epidemiologic evidence regarding the role of endogenous sex hormones in endometrial cancer etiology remains inconsistent. The objective of this study was to investigate if circulating levels of endogenous estrone, estradiol, sex hormone binding globulin (SHBG), testosterone, and androstenedione are associated with endometrial cancer risk. METHODS: We conducted a population-based case-control study of 522 incident endometrial cancer cases and 976 population controls, in Alberta, Canada from 2002 to 2006. Study participants completed in-person interviews and provided fasting blood samples. Sex hormone levels were determined by enzyme-linked immunosorbent assays. RESULTS: Higher levels of androstenedione were associated with increased endometrial cancer risk (OR 1.44, 95% CI 1.04-2.02). Endometrial cancer risk in pre- and peri-menopausal women was reduced for the highest versus lowest quartiles of estrone (OR 0.44, 95% CI 0.22-0.88) and estradiol (OR 0.30, 95% CI 0.14-0.65), but in post-menopausal women, the endometrial cancer risk was increased for the highest versus lowest quartile of androstenedione (OR 1.82, 95% CI 1.25-2.65). In addition, endometrial cancer risk in normal/underweight women was decreased for the highest versus lowest quartile of serum SHBG (OR 0.39, 95% CI 0.19-0.84). CONCLUSIONS: Overall, positive associations were found for androstenedione concentrations, while sub-group analyses revealed = inverse associations with estrogens and SHBG. Results of this study provide empirical evidence for the role of circulating sex hormones in endometrial cancer etiology and highlight the importance of modifiable factors that contribute to changes in sex hormone concentration levels.
BACKGROUND: Epidemiologic evidence regarding the role of endogenous sex hormones in endometrial cancer etiology remains inconsistent. The objective of this study was to investigate if circulating levels of endogenous estrone, estradiol, sex hormone binding globulin (SHBG), testosterone, and androstenedione are associated with endometrial cancer risk. METHODS: We conducted a population-based case-control study of 522 incident endometrial cancer cases and 976 population controls, in Alberta, Canada from 2002 to 2006. Study participants completed in-person interviews and provided fasting blood samples. Sex hormone levels were determined by enzyme-linked immunosorbent assays. RESULTS: Higher levels of androstenedione were associated with increased endometrial cancer risk (OR 1.44, 95% CI 1.04-2.02). Endometrial cancer risk in pre- and peri-menopausal women was reduced for the highest versus lowest quartiles of estrone (OR 0.44, 95% CI 0.22-0.88) and estradiol (OR 0.30, 95% CI 0.14-0.65), but in post-menopausal women, the endometrial cancer risk was increased for the highest versus lowest quartile of androstenedione (OR 1.82, 95% CI 1.25-2.65). In addition, endometrial cancer risk in normal/underweight women was decreased for the highest versus lowest quartile of serum SHBG (OR 0.39, 95% CI 0.19-0.84). CONCLUSIONS: Overall, positive associations were found for androstenedione concentrations, while sub-group analyses revealed = inverse associations with estrogens and SHBG. Results of this study provide empirical evidence for the role of circulating sex hormones in endometrial cancer etiology and highlight the importance of modifiable factors that contribute to changes in sex hormone concentration levels.