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Associations of Sex Steroid Hormones with Liver Cancer Incidence in Women

This study explores the links between circulating sex steroid hormones and primary liver cancer among women, offering insights into risk factors and prevalence differences by sex. Using epidemiological and experimental evidence, the research investigates the roles of estrogens and androgens in liver cancer development. Prediagnostic hormone concentrations were analyzed in relation to liver cancer incidence, with findings indicating potential protective effects of estrogens and detrimental effects of androgens. The study population comprised 191 liver cancer cases and 426 controls, matched based on parent cohort, age, race/ethnicity, and date of blood draw. The statistical analysis included conditional logistic regression to adjust for various factors such as age, body mass index, smoking status, and hormonal therapy. Results highlighted significant associations with androstenedione, SHBG, and estradiol levels, emphasizing their impact on intrahepatic cholangiocarcinoma risk. This research sheds light on the complex interplay between sex hormones and liver cancer in women.

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Associations of Sex Steroid Hormones with Liver Cancer Incidence in Women

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  1. Associations between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Primary Liver Cancer Among Women Jessica L. Petrick, PhD, MPH Assistant Professor of Medicine September 21, 2019 Slone Epidemiology Center at Boston University

  2. Disclosure Information ILCA 2019Jessica L. Petrick I have no financial relationships to disclose. Slone Epidemiology Center at Boston University

  3. Liver cancer rates 2-3 times higher in men than women France SwitzerlandSpain USA M:F Ratio HCC: 3.7:1 ICC: 1.3:1 SEER 18 2000-2015 Introduction | Methods | Results | Conclusions | 2 Slone Epidemiology Center at Boston University Petrick et al., 2019 Female Male

  4. Risk factors differ in prevalence by sex Introduction | Methods | Results | Conclusions | 3 Slone Epidemiology Center at Boston University

  5. Sex steroid hormones proposed to underlie sex differences Estrogens beneficial Androgens detrimental Experimental Studies • Female rodents: testosterone or ovariectomy ↑ liver cancer development • Male rodents: estrogen or castration ↓ liver cancer development Epidemiology Studies • Women: oophorectomy ↑ liver cancer risk • Men: higher testosterone levels ↑ liver cancer risk Introduction | Methods | Results | Conclusions | 4 Slone Epidemiology Center at Boston University McGlynn et al., 2015; Nakatani et al., 2001; Kamada et al., 2011; Yuan et al., 1995

  6. Primary Aim Prediagnostic circulating sex steroid hormones → prospectively ascertained liver cancer incidence Introduction | Methods | Results | Conclusions | 5 Slone Epidemiology Center at Boston University

  7. Study Population: Liver Cancer Pooling Project Introduction | Methods | Results | Conclusions | 6 Slone Epidemiology Center at Boston University

  8. Study Population: Liver Cancer Pooling Project Introduction | Methods | Results | Conclusions | 6 Slone Epidemiology Center at Boston University

  9. Study Population: Liver Cancer Pooling Project Introduction | Methods | Results | Conclusions | 6 Slone Epidemiology Center at Boston University

  10. Study Population: Liver Cancer Pooling Project Introduction | Methods | Results | Conclusions | 6 Slone Epidemiology Center at Boston University

  11. Study Population: Liver Cancer Pooling Project Introduction | Methods | Results | Conclusions | 6 Slone Epidemiology Center at Boston University

  12. Study Population 191 liver cancer cases and 426 controls • Matched on: Parent cohort Age Race/ethnicity Date of blood draw Introduction | Methods | Results | Conclusions | 7 Slone Epidemiology Center at Boston University

  13. Outcomes defined using ICD Primary liver cancer • ICD-10: C22 Hepatocellular Carcinoma • ICD-O-3: 8170-8175 Intrahepatic Cholangiocarcinoma • ICD-O-3: 8032-8033, 8041, 8050, 8070-8071, 8140-8141, 8160, 8260, 8480, 8481, 8490, 8560 Intrahepatic Bile Ducts Perihilar bile ducts Distal bile ducts Introduction | Methods | Results | Conclusions | 8 Liver Bowel Pancreas Cancer Research UK Slone Epidemiology Center at Boston University

  14. Exposures Sex Steroid Hormones • Gas chromatography-mass spectrometry (GC-MS) Sex hormone-binding globulin (SHBG) • Electrochemiluminescence immunoassay Introduction | Methods | Results | Conclusions | 9 Slone Epidemiology Center at Boston University

  15. Statistical Analysis Coefficients of variation <20% Conditional logistic regression analysis • Exposure: log2 transformed hormone values • Per unit increase represents a doubling of hormone concentration • Adjusted: • Age at blood draw • Body mass index • Smoking status • Alcohol consumption • HBV surface antigen • HCV antibody • Diabetes • Menopausal hormone therapy Introduction | Methods | Results | Conclusions | 10 Slone Epidemiology Center at Boston University

  16. Estrogens and SHBG Introduction | Methods | Results | Conclusions | 11 Slone Epidemiology Center at Boston University

  17. Estrogens and SHBG Introduction | Methods | Results | Conclusions | 11 Slone Epidemiology Center at Boston University

  18. Estrogens and SHBG Introduction | Methods | Results | Conclusions | 11 Slone Epidemiology Center at Boston University

  19. Estrogens and SHBG Introduction | Methods | Results | Conclusions | 11 Slone Epidemiology Center at Boston University

  20. Estrogens and SHBG Introduction | Methods | Results | Conclusions | 11 Slone Epidemiology Center at Boston University

  21. Estrogens and SHBG Introduction | Methods | Results | Conclusions | 11 Slone Epidemiology Center at Boston University

  22. Androgens and DHEA Introduction | Methods | Results | Conclusions | 12 Slone Epidemiology Center at Boston University

  23. Androgens and DHEA Introduction | Methods | Results | Conclusions | 12 Slone Epidemiology Center at Boston University

  24. Androgens and DHEA Introduction | Methods | Results | Conclusions | 12 Slone Epidemiology Center at Boston University

  25. Summary of Results Androstenedione: ↓50% risk SHBG: ↑31% risk Estradiol: ↑40% ICC risk, ↔ HCC Null associations with all other hormones Introduction | Methods | Results | Conclusions | 13 Slone Epidemiology Center at Boston University

  26. Conclusions Higher levels of circulating androstenedione may be associated with lower, and SHBG higher, risks of liver cancer Does not support hypothesis that estrogen decreases liver cancer risk; indeed, estradiol may increase ICC risk May partially explain the lower sex differences between ICC compared to HCC Introduction | Methods | Results | Conclusions | 14 Slone Epidemiology Center at Boston University

  27. Acknowledgements Andrea A. Florio, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Jean Wactawski-Wende, Stephen K. Van Den Eeden, Frank Z. Stanczyk, Tracey G. Simon, Rashmi Sinha, Howard D. Sesso, Catherine Schairer, Lynn Rosenberg, Thomas E. Rohan, Mark P. Purdue, Julie R. Palmer, Martha S. Linet, Linda M. Liao, I-Min Lee, Jill Koshiol, Cari M. Kitahara, Victoria A. Kirsh, Jonathan N. Hoffman, Chantal Guillemette, Barry I. Graubard, Edward Giovannucci, J. Michael Gaziano, Susan M. Gapster, Neal D. Freedman, Lawrence S. Engel, Dawn Q. Chong, Yu Chen, Andrew T. Chan, Patrick Caron, Julie E. Buring, Gary Bradwin, Laura E. Beane Freeman, Peter T. Campbell, Katherine A. McGlynn Slone Epidemiology Center at Boston University

  28. Questions? Jessica Petrick, PhD, MPH Slone Epidemiology Center at Boston University jpetrick@bu.edu Slone Epidemiology Center at Boston University

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