男性基线血清甾体激素代谢标志物与食管癌及癌前病变风险的关系:一项前瞻性队列研究  

Associations Between Pre-Diagnostic Serum Sex Steroid Hormone Metabolites and Esophageal Cancer and Precancerous Lesions in Men:A Prospective Cohort Study

作　　者：李佳悦 贺非凡 范志园 薛丽燕 饶薇 王宗丹 顾建华 李新庆 郝长青[3] 崔巍 魏文强 王少明 LI Jiayue;HE Feifan;FAN Zhiyuan;XUE Liyan;RAO Wei;WANG Zongdan;GU Jianhua;LI Xinqing;HAO Changqing;CUI Wei;WEI Wenqiang;WANG Shaoming(National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Qilu Hospital of Shandong University,Jinan 250117,China;Linzhou City Cancer Hospital,Linzhou 456550,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院,北京100021 [2]山东大学齐鲁医院,山东济南250117 [3]林州市肿瘤医院,河南林州456550

出　　处：《中国肿瘤》2024年第9期731-746,共16页China Cancer

基　　金：国家自然科学基金(81502864);北京市科技新星计划(Z201100006820069);中国医学科学院医学与健康科技创新工程(2019-I2M-2-004,2021-I2M-1-023);中国医学科学院肿瘤医院人才激励计划(希望之星)。

摘　　要：[目的]探讨甾体激素代谢标志物与食管癌及癌前病变风险的相关性。[方法] 2007—2012年,选取上消化道癌高发区男性筛查队列中经病理诊断为高级别病变或食管癌患者52例,低级别病变病例100例,以及正常参与者374人。采用高效液相色谱法检测基线血清中20种甾体激素代谢标志物水平,利用电化学发光免疫分析检测性激素结合球蛋白水平。随访至2021年12月,收集食管癌发病和死亡情况。采用Logistic回归分析甾体激素代谢标志物与食管癌及癌前病变(高级别和低级别病变)风险的相关性;采用Cox比例风险回归评估基线甾体激素代谢标志物与食管癌发病风险的关系。[结果]较高的性激素结合球蛋白水平可能与较低的食管癌及癌前病变风险有关,而表睾酮和2-甲氧雌酮水平较高的参与者发生食管癌及癌前病变风险较高。在中位11.8年的前瞻性随访期间,在基线诊断为正常或低级别病变的参与者中发现29例食管癌新发病例,研究发现较高水平的雄烯二酮(HR:Q4vs Q1=4.93;95%CI:1.06~22.93)可能与食管癌风险增加相关。[结论]部分甾体激素代谢标志物可能在食管癌的致癌机制中发挥作用,有望为食管癌的病因学研究、高危人群识别及风险预警提供新型标志物。[Purpose]To investigate the associations between sex steroid hormone metabolites and esophageal cancer(EC)and precancerous lesions risk in a prospective Chinese male screening cohort.[Methods]We selected pathologically confirmed high-grade lesions or EC cases(n=52),lowgrade lesions cases(n=100),and normal participants(n=374)from the male upper gastrointestinal cancer screening cohort from 2007 to 2012.We tested 20 sex steroid hormone metabolites in the baseline serum by using high-performance liquid chromatography and tested sex hormone-binding globulin(SHBG)with the electrochemical luminescence immunoassay.Participants were followed up until December 2021 for the incidence and mortality rate of EC.Logistic regression analysis was used to calculate associations between sex steroid hormone metabolites and esophageal cancer and precancerous lesions(high-grade and low-grade lesions).Cox proportional hazards regression was used to calculate associations between pre-diagnostic sex steroid hormone metabolites and EC risk.[Results]In the cross-sectional analysis,we found that higher levels of SHBG may be associated with a lower risk of esophageal cancer and precancerous lesions,but participants with higher levels of epitestosterone and 2-methoxyestrone had higher risk of being diagnosed with esophageal cancer and precancerous lesions.During a prospective follow-up of 11.8 years,29 new cases of EC were identified among the participants diagnosed with normal or low-grade lesions.The results suggested that higher levels of androstenedione(HR:Q4 vs Q1=4.93;95%CI:1.06~22.93)may be associated with an increased EC risk.[Conclusion]The study suggests that several sex steroid hormone metabolites may play a role in the carcinogenesis of EC.These findings may help provide novel biomarkers for the study of the etiology,the identification of high-risk populations and risk prediction of EC.

关 键 词：血清甾体激素代谢标志物 食管癌 前瞻性队列研究 

分 类 号：R735.1[医药卫生—肿瘤]