TY - JOUR
T1 - Endogenous sex steroid hormones and risk of liver cancer among US men
T2 - Results from the Liver Cancer Pooling Project
AU - Wu, Zeni
AU - Petrick, Jessica L.
AU - Florio, Andrea A.
AU - Guillemette, Chantal
AU - Beane Freeman, Laura E.
AU - Buring, Julie E.
AU - Bradwin, Gary
AU - Caron, Patrick
AU - Chen, Yu
AU - Eliassen, A. Heather
AU - Engel, Lawrence S.
AU - Freedman, Neal D.
AU - Gaziano, J. Michael
AU - Giovannuci, Edward L.
AU - Hofmann, Jonathan N.
AU - Huang, Wen Yi
AU - Kirsh, Victoria A.
AU - Kitahara, Cari M.
AU - Koshiol, Jill
AU - Lee, I. Min
AU - Liao, Linda M.
AU - Newton, Christina C.
AU - Palmer, Julie R.
AU - Purdue, Mark P.
AU - Rohan, Thomas E.
AU - Rosenberg, Lynn
AU - Sesso, Howard D.
AU - Sinha, Rashmi
AU - Stampfer, Meir J.
AU - Um, Caroline Y.
AU - Van Den Eeden, Stephen K.
AU - Visvanathan, Kala
AU - Wactawski-Wende, Jean
AU - Zeleniuch-Jacquotte, Anne
AU - Zhang, Xuehong
AU - Graubard, Barry I.
AU - Campbell, Peter T.
AU - McGlynn, Katherine A.
N1 - Publisher Copyright:
© 2023
PY - 2023/7
Y1 - 2023/7
N2 - Background & Aims: Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. Methods: Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. Results: Higher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). Conclusions: Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implications: This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.
AB - Background & Aims: Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. Methods: Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. Results: Higher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). Conclusions: Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implications: This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.
KW - Androgen
KW - Liver cancer
KW - Male
KW - Oestrogen
KW - Sex steroid hormone
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U2 - 10.1016/j.jhepr.2023.100742
DO - 10.1016/j.jhepr.2023.100742
M3 - Article
AN - SCOPUS:85159925557
SN - 2589-5559
VL - 5
JO - JHEP Reports
JF - JHEP Reports
IS - 7
M1 - 100742
ER -