Wu Zeni, Petrick Jessica L, Florio Andrea A, Guillemette Chantal, Beane Freeman Laura E, Buring Julie E, Bradwin Gary, Caron Patrick, Chen Yu, Eliassen A Heather, Engel Lawrence S, Freedman Neal D, Gaziano J Michael, Giovannuci Edward L, Hofmann Jonathan N, Huang Wen-Yi, Kirsh Victoria A, Kitahara Cari M, Koshiol Jill, Lee I-Min, Liao Linda M, Newton Christina C, Palmer Julie R, Purdue Mark P, Rohan Thomas E, Rosenberg Lynn, Sesso Howard D, Sinha Rashmi, Stampfer Meir J, Um Caroline Y, Van Den Eeden Stephen K, Visvanathan Kala, Wactawski-Wende Jean, Zeleniuch-Jacquotte Anne, Zhang Xuehong, Graubard Barry I, Campbell Peter T, McGlynn Katherine A
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Slone Epidemiology Center, Boston University, Boston, MA, USA.
JHEP Rep. 2023 Mar 22;5(7):100742. doi: 10.1016/j.jhepr.2023.100742. eCollection 2023 Jul.
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.
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.
Higher concentrations of total testosterone (OR per one-unit increase in log = 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).
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.
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.
在大多数人群中，男性肝癌发病率是女性的两到三倍。男性发病率较高这一情况表明，雄激素与风险增加有关，而雌激素与风险降低有关。本研究通过对美国五个队列中男性诊断前性类固醇激素水平进行巢式病例对照分析，对这一假设进行了调查。
分别使用气相色谱 - 质谱法和竞争性电化学发光免疫分析法对性类固醇激素和性激素结合球蛋白的浓度进行定量。采用多变量条件逻辑回归计算275例随后发生肝癌的男性和768例对照男性中激素与肝癌之间关联的比值比（OR）和95%置信区间（CI）。
总睾酮（对数每增加一个单位，OR = 1.77，95% CI = 1.38 - 2.29）、二氢睾酮（OR = 1.76，95% CI = 1.21 - 2.57）、雌酮（OR = 1.74，95% CI = 1.08 - 2.79）、总雌二醇（OR = 1.58，95% CI = 1.22 - 20.05）和性激素结合球蛋白（OR = 1.63，95% CI = 1.27 - 2.11）浓度较高与风险增加相关。然而，脱氢表雄酮（DHEA）浓度较高与风险降低53%相关（OR = 0.47，95% CI = 0.33 - 0.68）。
与未患肝癌的男性相比，随后发生肝癌的男性体内雄激素（睾酮、二氢睾酮）及其芳香化雌激素代谢产物（雌酮、雌二醇）浓度均较高。由于DHEA是雄激素和雌激素的肾上腺前体，这些结果可能表明，将DHEA转化为雄激素及其随后转化为雌激素的能力较低会降低患肝癌的风险，而将DHEA转化的能力较强则会增加风险。
本研究并不完全支持当前的激素假说，因为雄激素和雌激素水平均与男性患肝癌风险增加有关。该研究还发现，较高的DHEA水平与较低风险相关，因此表明将DHEA转化的能力较强可能与男性患肝癌风险增加有关这一假说。
