代谢因子与肝细胞癌关联的性别差异

StephenW

Gender Difference in the Association Between Metabolic Factors and Hepatocellular Carcinoma
Chi-Ling Chen  1   2   3 , Ming-Jeng Kuo  2   4 , Amy Ming-Fang Yen  2   5 , Wei-Shiung Yang  1   6   7 , Jia-Horng Kao  1   6   7 , Pei-Jer Chen  1   6   7 , Hsiu-Hsi Chen  1   2
Affiliations
Affiliations

    1
    Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
    2
    Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
    3
    Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
    4
    Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan.
    5
    School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
    6
    Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
    7
    Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

    PMID: 33134821 PMCID: PMC7583157 DOI: 10.1093/jncics/pkaa036

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Abstract

Background: A gender difference in hepatocellular carcinoma (HCC) that men have higher incidence than women has long been noted and can be explained by the cross-talk between sex hormones and hepatitis B virus/hepatitis C virus (HBV/HCV). Whether metabolic factors yield similar sexual difference in non-HBV/HCV-HCC remains elusive.

Methods: There were 74 782 hepatitis B surface antigen (HBsAg)/antibody to hepatitis C virus (anti-HCV) negative residents who participated in the Keelung Community-Based Integrated Screening program and were followed in 2000-2007. Incident HCC was identified by linkage to the Taiwan Cancer Registry. Cox proportional hazards regression models were used to estimate the association between metabolic factors and HCC stratified by sex. All statistical tests were 2-sided.

Results: With 320 829 follow-up person-years, 99 residents developed HCC. The adjusted hazard ratios (aHR) were 2.10 (95% confidence interval [CI] = 1.07 to 4.13) and 3.71 (95% CI = 2.01 to 6.86) for prediabetes and diabetes, respectively, in men. The corresponding adjusted hazard ratios were 1.16 (95% CI = 0.48 to 2.83) and 1.47 (95% CI = 0.65 to 3.34) in women. Compared with normal weight (body mass index [BMI] = 23-25), underweight (BMI < 21, HR = 3.56, 95% CI = 1.18 to 10.8) and overweight (BMI = 25 to <27.3, HR = 3.81, 95% CI = 1.43 to 10.2) were associated with an elevated risk in men. The statistically significant gradient relationship per advanced BMI category was noted in women (aHR = 1.41, 95% CI = 1.07 to 1.87). The HCC-fasting glucose (P = .046) and HCC-BMI (P = .03) associations were statistically significantly modified by sex. Elevated aspartate aminotransferase, aspartate aminotransferase-to-platelet index and fibrosis index, and habitual alcohol consumption were related to HCC only in men, whereas increased alanine aminotransferase and lower platelet levels predicted HCC risk in women.

Conclusions: We found that BMI-HCC associations were U-shape for men and linear for women, and the elevated HCC risk began from glucose impairment in men only. Whether good glycemic and weight control can reduce HCC risk warrants further investigation.

© The Author(s) 2020. Published by Oxford University Press.

StephenW

代谢因子与肝细胞癌关联的性别差异
陈志玲1 2 3，郭明正2 4，颜爱芳2 5，杨维雄1 6 7，高嘉鸿1 6 7，陈佩杰1 6 7，秀西陈1 2
隶属关系
隶属关系

    1个
    国立台湾大学医学院临床医学研究所，台湾台北。
    2
    国立台湾大学公共卫生学院流行病学和预防医学研究所，台湾台北。
    3
    国立台湾大学医院外科，台湾台北。
    4
    台湾台南市台南市立医院消化内科。
    5
    台北医科大学口腔医学院口腔卫生学院，台湾台北。
    6
    国立台湾大学附属医院内科，台湾台北。
    7
    国立台湾大学附属医院肝炎研究中心，台湾台北。

    PMID：33134821 PMCID：PMC7583157 DOI：10.1093 / jncics / pkaa036

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抽象

背景：肝细胞癌（HCC）的性别差异长期以来被注意到，即男性比女性发病率更高，这可以通过性激素与乙型肝炎病毒/丙型肝炎病毒（HBV / HCV）之间的相互影响来解释。代谢因素是否在非HBV / HCV-HCC中产生相似的性别差异仍不清楚。

方法：2000-2007年参加基隆社区基础综合筛查计划并随访了74782例乙型肝炎表面抗原（HBsAg）/丙型肝炎病毒（anti-HCV）阴性抗体。通过与台湾癌症登记处的联系确定了HCC事件。使用Cox比例风险回归模型估计代谢因子与按性别分层的HCC之间的关联。所有统计检验均为2面检验。

结果：随访320 829人-年，有99位居民发展了HCC。男性前驱糖尿病和糖尿病患者的调整后风险比（aHR）分别为2.10（95％置信区间[CI] = 1.07至4.13）和3.71（95％CI = 2.01至6.86）。女性相应的调整后危险比为1.16（95％CI = 0.48至2.83）和1.47（95％CI = 0.65至3.34）。与正常体重（体重指数[BMI] = 23-25）相比，体重不足（BMI <21，HR = 3.56，95％CI = 1.18至10.8）和超重（BMI = 25至<27.3，HR = 3.81，95 ％CI = 1.43至10.2）与男性风险升高相关。在女性中，每个晚期BMI类别的统计学显着梯度关系均已注意到（aHR = 1.41，95％CI = 1.07至1.87）。性别对HCC空腹血糖（P = .046）和HCC-BMI（P = .03）的关联有统计学显着影响。天冬氨酸转氨酶，天冬氨酸转氨酶-血小板指数和纤维化指数以及习惯性饮酒仅与男性HCC相关，而丙氨酸转氨酶升高和较低的血小板水平则预示女性发生HCC的危险。

结论：我们发现男性的BMI-HCC关联呈U形，女性呈线性，并且升高的HCC风险仅从男性的葡萄糖受损开始。良好的血糖控制和体重控制能否降低HCC风险值得进一步研究。

©2020作者。牛津大学出版社出版。

StephenW

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