1. Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women
- Author
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Julie E. Buring, Rashmi Sinha, Edward Giovannucci, Gary Bradwin, Victoria A. Kirsh, Anne Zeleniuch-Jacquotte, Lynn Rosenberg, Julie R. Palmer, Catherine Schairer, Jessica L. Petrick, Tracey G. Simon, Jonathan N. Hofmann, Chantal Guillemette, Linda M. Liao, Mark P. Purdue, Jill Koshiol, Lawrence S. Engel, Stephen K. Van Den Eeden, Dawn Q. Chong, Katherine A. McGlynn, Neal D. Freedman, Andrew T. Chan, J. Michael Gaziano, Frank Z. Stanczyk, Susan M. Gapster, Laura E. Beane Freeman, Cari M. Kitahara, Peter T. Campbell, Xuehong Zhang, Thomas E. Rohan, I-Min Lee, Jean Wactawski-Wende, Andrea A. Florio, Howard D. Sesso, Martha S. Linet, Barry I. Graubard, Yu Chen, and Patrick Caron
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,medicine.drug_class ,Physiology ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Sex hormone-binding globulin ,Sex Factors ,Sex Hormone-Binding Globulin ,medicine ,Humans ,Gonadal Steroid Hormones ,Aged ,Hepatology ,biology ,business.industry ,Liver Neoplasms ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Postmenopause ,030104 developmental biology ,Estrogen ,Hepatocellular carcinoma ,Cohort ,biology.protein ,030211 gastroenterology & hepatology ,Female ,Liver cancer ,business ,Hormone - Abstract
Background In almost all countries, incidence rates of liver cancer are 100-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of liver cancer cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with liver cancer risk, overall and by histology, by leveraging resources from five prospective cohorts. Methods Seven sex steroid hormones and SHBG were quantitated using gas chromatography-tandem mass spectrometry (GC-MS/MS) and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 post-menopausal female liver cancer cases (HCC n=83, ICC n=56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one-unit increase in log2 hormone value (approximate doubling of circulating concentration) and liver cancer were calculated using multivariable-adjusted conditional logistic regression. Results A doubling in the concentration of 4-androstenedione was associated with a 50% decreased liver cancer risk (OR=0.50,95%CI=0.30-0.82), while SHBG was associated with a 31% increased risk (OR=1.31,95%CI=1.05-1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR=1.40,95%CI=1.05-1.89), but not HCC (OR=1.12,95%CI=0.81-1.54). Conclusions This study provides the first evidence that higher levels of 4-androstenedione may be associated with lower, and SHBG with higher, liver cancer risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease liver cancer risk. Indeed, estradiol may be associated with an increased ICC risk.
- Published
- 2019