C Kilander1, J Lagergren1,2, P Konings1,3, O Sadr-Azodi4,5, N Brusselaers6,7. 1. a Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery , Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden. 2. b Division of Cancer Studies , King's College London , London , UK. 3. c Department of Quantitative Biology , Discovery Sciences, IMED Biotech Unit, AstraZeneca , Gothenburg , Sweden. 4. d Department of Environmental Medicine , Karolinska Institutet , Stockholm , Sweden. 5. e Center for Clinical Research: Sörmland , Uppsala University , Uppsala , Sweden. 6. f Centre for Translational Microbiome Research, Department of Microbiology , Tumor and Cell biology, Karolinska Institutet, Karolinska Hospital , Stockholm , Sweden. 7. g Science for Life Laboratory , Stockholm , Sweden.
Abstract
BACKGROUND: This study tested the hypothesis that contemporary menopausal hormonal therapy (MHT) increases the risk of biliary tract cancer. The risk of cancer of the biliary tract (gallbladder and extra-hepatic bile ducts) may be increased following estrogen exposure. MATERIAL AND METHODS: This was a nationwide population-based matched cohort study in Sweden. Data from the Swedish Prescribed Drug Register identified all women exposed to systemic MHT in 2005-2012. Group-level matching (1:3 ratio) was used to select women unexposed to MHT from the same study base, matched for history of delivery, thrombotic events, hysterectomy, age, smoking- and alcohol related diseases, obesity, and diabetes. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Comparing 290,186 women exposed to MHT with 870,165 unexposed, MHT did not increase the OR of biliary tract cancer. The OR of gallbladder cancer was rather decreased in MHT users (OR 0.58, 95% CI 0.43-0.79), but this association became attenuated and statistically non-significant after adjusting for gallstone disease (OR 0.84, 95% CI 0.60-1.15). The OR of extra-hepatic bile duct cancers was 0.83 (95% CI 0.61-1.15). There were no clear differences when the analyses were stratified for estrogen or estrogen/progestogen combinations. MHT increased the risk of gallstone disease (OR 6.95, 95% CI 6.64-7.28). CONCLUSIONS: Contemporary MHT does not seem to increase the risk of biliary tract cancer. The decreased risk of gallbladder cancer may be explained by the increased use of surgery for symptomatic gallstones in MHT users.
BACKGROUND: This study tested the hypothesis that contemporary menopausal hormonal therapy (MHT) increases the risk of biliary tract cancer. The risk of cancer of the biliary tract (gallbladder and extra-hepatic bile ducts) may be increased following estrogen exposure. MATERIAL AND METHODS: This was a nationwide population-based matched cohort study in Sweden. Data from the Swedish Prescribed Drug Register identified all women exposed to systemic MHT in 2005-2012. Group-level matching (1:3 ratio) was used to select women unexposed to MHT from the same study base, matched for history of delivery, thrombotic events, hysterectomy, age, smoking- and alcohol related diseases, obesity, and diabetes. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Comparing 290,186 women exposed to MHT with 870,165 unexposed, MHT did not increase the OR of biliary tract cancer. The OR of gallbladder cancer was rather decreased in MHT users (OR 0.58, 95% CI 0.43-0.79), but this association became attenuated and statistically non-significant after adjusting for gallstone disease (OR 0.84, 95% CI 0.60-1.15). The OR of extra-hepatic bile duct cancers was 0.83 (95% CI 0.61-1.15). There were no clear differences when the analyses were stratified for estrogen or estrogen/progestogen combinations. MHT increased the risk of gallstone disease (OR 6.95, 95% CI 6.64-7.28). CONCLUSIONS: Contemporary MHT does not seem to increase the risk of biliary tract cancer. The decreased risk of gallbladder cancer may be explained by the increased use of surgery for symptomatic gallstones in MHT users.
Authors: Sarah S Jackson; Hans-Olov Adami; Gabriella Andreotti; Laura E Beane-Freeman; Amy Berrington de González; Julie E Buring; Gary E Fraser; Neal D Freedman; Susan M Gapstur; Gretchen Gierach; Graham G Giles; Francine Grodstein; Patricia Hartge; Mazda Jenab; Victoria Kirsh; Synnove F Knutsen; Qing Lan; Susanna C Larsson; I-Min Lee; Mei-Hsuan Lee; Linda M Liao; Roger L Milne; Kristine R Monroe; Marian L Neuhouser; Katie M O'Brien; Jessica L Petrick; Mark P Purdue; Thomas E Rohan; Sven Sandin; Dale P Sandler; Norie Sawada; Aladdin H Shadyab; Tracey G Simon; Rashmi Sinha; Rachael Stolzenberg-Solomon; Shoichiro Tsugane; Elisabete Weiderpass; Alicja Wolk; Hwai-I Yang; Wei Zheng; Katherine A McGlynn; Peter T Campbell; Jill Koshiol Journal: J Hepatol Date: 2020-05-11 Impact factor: 25.083