肝功能生物标志物与肝胆癌发生的前瞻性关联。
Prospective association of liver function biomarkers with development of hepatobiliary cancers.
作者信息
Stepien Magdalena, Fedirko Veronika, Duarte-Salles Talita, Ferrari Pietro, Freisling Heinz, Trepo Elisabeth, Trichopoulou Antonia, Bamia Christina, Weiderpass Elisabete, Olsen Anja, Tjønneland Anne, Overvad Kim, Boutron-Ruault Marie-Christine, Fagherazzi Guy, Racine Antoine, Kühn Tilman, Kaaks Rudolf, Aleksandrova Krasimira, Boeing Heiner, Lagiou Pagona, Benetou Vassiliki, Trichopoulos Dimitrios, Palli Domenico, Grioni Sara, Tumino Rosario, Naccarati Alessio, Panico Salvatore, Bueno-de-Mesquita H Bas, Peeters Petra H, Lund Eiliv, Quirós J Ramón, Nápoles Osmel Companioni, Sánchez María-José, Dorronsoro Miren, Huerta José María, Ardanaz Eva, Ohlsson Bodil, Sjöberg Klas, Werner Mårten, Nystrom Hanna, Khaw Kay-Tee, Key Timothy J, Gunter Marc, Cross Amanda, Riboli Elio, Romieu Isabelle, Jenab Mazda
机构信息
Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA.
出版信息
Cancer Epidemiol. 2016 Feb;40:179-87. doi: 10.1016/j.canep.2016.01.002. Epub 2016 Jan 11.
INTRODUCTION
Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.
METHODS
A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).
RESULTS
In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).
CONCLUSION
This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.
引言
血清肝脏生物标志物（γ-谷氨酰转移酶，GGT；丙氨酸氨基转移酶，ALT；天冬氨酸氨基转移酶，AST；碱性磷酸酶，ALP；总胆红素）被用作肝病指标，但目前关于它们与肝胆癌风险的前瞻性关联的数据很少。
方法
在前瞻性的欧洲癌症与营养前瞻性调查（EPIC）队列（超过520,000名参与者，10个欧洲国家）中进行了一项巢式病例对照研究。经过平均7.5年的随访，确定了121例肝细胞癌（HCC）、34例肝内胆管癌（IHBC）和131例胆囊及胆道癌（GBTC）病例，并为每个病例匹配2名对照。在队列入组时、癌症诊断之前采集的血清中测量循环生物标志物。使用多变量调整的条件逻辑回归来计算比值比和95%置信区间（OR；95%CI）。
结果
在多变量模型中，每个对数转换后的生物标志物增加1个标准差与HCC风险呈正相关（OR（GGT）=4.23，95%CI：2.72 - 6.59；OR（ALP）=3.43，95%CI：2.31 - 5.10；OR（AST）=3.00，95%CI：2.04 - 4.42；OR（ALT）=2.69，95%CI：1.89 - 3.84；OR（胆红素）=2.25，95%CI：1.58 - 3.20）。每种肝酶（OR（GGT）=4.98；95%CI：1.75 - 14.17；OR（AST）=3.10，95%CI：1.04 - 9.30；OR（ALT）=2.86，95%CI：1.26 - 6.48，OR（ALP）=2.31，95%CI：1.10 - 4.86）但胆红素（OR（胆红素）=1.46，95%CI：0.85 - 2.51）与IHBC呈显著关联。仅ALP与GBTC风险显著相关（OR（ALP）=1.59，95%CI：1.20 - 2.09）。
结论
本研究表明，在癌症诊断之前采集的血清中循环肝脏生物标志物与发生HCC或IHBC的风险之间存在正相关，但与GBTC无关。
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