Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study

American Journal of Epidemiology, Feb 2010

Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995–2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR = 0.69, 95% CI: 0.52, 0.92; Ptrend = 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer (Pheterogeneity = 0.04). Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study.

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Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study

American Journal of Epidemiology ª The Author 2010. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions Original Contribution Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer The California Teachers Study 0 Katherine DeLellis Henderson 0 Lei Duan 0 Jane Sullivan-Halley 0 Huiyan Ma 0 Christina A. Clarke 0 Susan L. Neuhausen 0 Claire Templeman 0 Leslie Bernstein 0 0 Research Institute, City of Hope National Medical Center , 1500 East Duarte Road, Duarte, CA 91010 , USA Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995-2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) ¼ 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR ¼ 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR ¼ 0.69, 95% CI: 0.52, 0.92; Ptrend ¼ 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer (Pheterogeneity ¼ 0.04). Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study. colonic neoplasms; hormone replacement therapy; lung neoplasms; parity; prospective studies; reproduction; smoking - Abbreviations: CI, confidence interval; HT, hormone therapy; Q2000, third California Teachers Study questionnaire sent in 2000; RR, relative risk; SD, standard deviation. Previous studies have shown that menopausal hormone therapy is associated with decreased risk of colon cancer ( 1 ). The Women’s Health Initiative trials found that continuous combined hormone therapy ( 2 ), but not unopposed estrogen therapy ( 3 ), was associated with decreased colorectal cancer risk. Those associations have been replicated ( 4 ) and disputed ( 5, 6 ) by subsequent studies. Few studies have investigated a possible dose-response between increasing duration of hormone therapy use and decreasing colon cancer risk. The Nurses’ Health Study reported no duration dose response but did report a strong reduction in risk among recent hormone therapy users, which was attenuated with increasing time since last use (7). In the current analysis, the association between colon cancer and hormone therapy use overall, by formulation, by duration of use, and by time since last use among women participating in the California Teachers Study was assessed. In addition, we investigated the extent to which several factors previously hypothesized to be associated with colon cancer risk, including physical activity ( 8, 9 ), body mass index ( 10, 11 ), regular nonsteroidal antiinflammatory drug use ( 12 ), calcium intake ( 13, 14 ), calcium plus vitamin D intake (15), family history of colorectal cancer ( 16 ), personal history of colorectal polyps ( 17 ), smoking history ( 18 ), and alcohol intake ( 19 ), might act as effect modifiers of the hormone therapy and colon cancer risk association or might appear to interact with hormone therapy in the context of colon cancer risk. MATERIALS AND METHODS The California Teachers Study is a prospective cohort of current and former female public school teachers and administrators, who were members of the California State Teachers Retirement System in 1995. Cohort participants completed a questionnaire, mailed in 1995, providing detailed information on factors such as hormone therapy use, personal medical history, reproductive history, physical activity, anthropometrics, medication use, diet, and family history of colorectal cancer. The third California Teachers Study questionnaire, sent in 2000 (Q2000), updated information on menopausal status and hormone therapy use. A detailed description of the California Teachers Study is available ( 20 ). Use of human subject data was approved by the institutional review boards at each collaborating institution in accord with assurances approved by the US Department of Health and Human Services. The California Teachers Study cohort comprises 133,479 women. Exclusions, in sequence, were women who, at baseline, lived outside California (n ¼ 8,867), had a prio (...truncated)


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Katherine DeLellis Henderson, Lei Duan, Jane Sullivan-Halley, Huiyan Ma, Christina A. Clarke, Susan L. Neuhausen, Claire Templeman, Leslie Bernstein. Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study, American Journal of Epidemiology, 2010, pp. 415-425, 171/4, DOI: 10.1093/aje/kwp434