TY - JOUR
T1 - Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women
AU - Petrick, Jessica L.
AU - Florio, Andrea A.
AU - Zhang, Xuehong
AU - Zeleniuch-Jacquotte, Anne
AU - Wactawski-Wende, Jean
AU - Van Den Eeden, Stephen K.
AU - Stanczyk, Frank Z.
AU - Simon, Tracey G.
AU - Sinha, Rashmi
AU - Sesso, Howard D.
AU - Schairer, Catherine
AU - Rosenberg, Lynn
AU - Rohan, Thomas E.
AU - Purdue, Mark P.
AU - Palmer, Julie R.
AU - Linet, Martha S.
AU - Liao, Linda M.
AU - Lee, I. Min
AU - Koshiol, Jill
AU - Kitahara, Cari M.
AU - Kirsh, Victoria A.
AU - Hofmann, Jonathan N.
AU - Guillemette, Chantal
AU - Graubard, Barry I.
AU - Giovannucci, Edward
AU - Gaziano, J. Michael
AU - Gapster, Susan M.
AU - Freedman, Neal D.
AU - Engel, Lawrence S.
AU - Chong, Dawn Q.
AU - Chen, Yu
AU - Chan, Andrew T.
AU - Caron, Patrick
AU - Buring, Julie E.
AU - Bradwin, Gary
AU - Beane Freeman, Laura E.
AU - Campbell, Peter T.
AU - McGlynn, Katherine A.
N1 - Publisher Copyright:
© 2020 by the American Association for the Study of Liver Diseases.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Background and Aims: In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC 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 LC risk, overall and by histology, by leveraging resources from five prospective cohorts. Approach and Results: Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC 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 LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas 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 evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.
AB - Background and Aims: In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC 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 LC risk, overall and by histology, by leveraging resources from five prospective cohorts. Approach and Results: Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC 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 LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas 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 evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.
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U2 - 10.1002/hep.31057
DO - 10.1002/hep.31057
M3 - Article
C2 - 31808181
AN - SCOPUS:85088411853
SN - 0270-9139
VL - 72
SP - 535
EP - 547
JO - Hepatology
JF - Hepatology
IS - 2
ER -
