恶性肿瘤与骨密度因果关系的双向两样本孟德尔随机化研究  

The causal relationship between cancer and bone mineral density:a bi-directional two-sample Mendelian randomization analysis

作　　者：陈天鑫 张智龙 朱瑜琪[1] 杨胜平 CHEN Tian-xin;ZHANG Zhi-ong;ZHU Yu-qi;YANG Sheng-ping(Department of Orthopedics,Eye Hospital China Academy of Chinese Medical Sciences,Beijing 100040,China;不详)

机构地区：[1]中国中医科学院眼科医院骨科,北京100040 [2]中国中医科学院望京医院 [3]中国中医科学院

出　　处：《现代预防医学》2023年第18期3276-3280,3287,共6页Modern Preventive Medicine

基　　金：国家中医药管理局中医药国际合作专项中心类项目(0610-2240NF0215);中国中医科学院科技创新工程(CI2021A020);第二届石景山区名中医传承工作室(朱瑜琪工作室2022)。

摘　　要：目的运用双向两样本孟德尔随机化的方法,探讨恶性肿瘤和骨质疏松之间的因果关系.方法从Finngen数据库获取20种恶性肿瘤(前列腺癌、淋巴和造血器官癌、膀胱癌、脑癌、乳腺癌、肺和支气管癌、宫颈癌、结肠癌、肾癌、喉癌、肝和肝内胆管癌、食管癌、卵巢癌、胰腺癌、直肠癌、皮肤癌、小肠癌、胃癌、睾丸癌、甲状腺癌)数据集,从GEFOS数据库获取全身骨密度(TB-BMD)数据集.运用逆方差加权法、加权中位数法和MR-Egger法等评估20种恶性肿瘤与TB-BMD的双向因果关系.采用Cochran Q检验、MR-Egger回归法和Leave-one-out法评价研究结果稳定性和可靠性.结果在乳腺癌、喉癌与TB-BMD的因果关系方面,观察到具有统计学意义的因果关系,其余18种恶性肿瘤与TB-BMD无显著因果关联.乳腺癌可能降低TB-BMD(β=-0.036,95%CI:-0.056~-0.015,P=0.001),喉癌可能增加TB-BMD(β=0.011,95%CI:0.002~0.021,P=0.022),结果具有统计学意义.加权中位数法和MR-Egger法与逆方差加权法关联方向一致.Cochran Q检验、MR-Egger回归和Leave-one-out法均提示本研究结果具有稳定性和可靠性.结论乳腺癌可能降低TB-BMD水平,喉癌可能增加TB-BMD水平.在临床实践中,乳腺癌患者重视骨密度筛查,及时干预骨质疏松.Objective To investigate the causal relationship between malignancy and osteoporosis using bi-directional two-sample Mendelian randomization.Methods A dataset of 20 malignancies(prostate cancer,lymphatic and hematopoietic organ cancer,bladder cancer,brain cancer,breast cancer,lung and bronchus cancer,cervical cancer,colon cancer,kidney cancer,laryngeal cancer,liver and intrahepatic bile duct cancer,esophageal cancer,ovarian cancer,pancreatic cancer,rectal cancer,skin cancer,small intestine cancer,gastric cancer,testicular cancer,thyroid cancer)was obtained from the Finngen database,and a dataset of whole-body bone mineral density(TB-BMD)was obtained from the GEFOS database.The inverse variance weighting method,weighted median method and MR-Egger method were used to assess the bi-directional causal relationship between 20 malignancies and osteoporosis risk.The Cochran Q test,MR-Egger regression method,and Leave-one-out were also used to evaluate the stability and reliability of the results.ResultsIn terms of causality between breast and laryngeal cancers and TB-BMD,statistically significant causality was observed,and the remaining 18 malignancies had no significant causal association with TB-BMD.Breast cancer may decrease TB-BMD(β=-0.036,95%CI:-0.056~-0.015,P=0.001)and laryngeal cancer may increase TB-BMD(β=0.011,95%CI:0.002~0.021,P=0.022),with statistically significant results Cochran Q test,MR-Egger regression,and Leave-one-out all suggest the stability and reliability of the results of this study.Conclusion Breast cancer may reduce TB-BMD levels and laryngeal cancer may increase TB-BMD levels.In clinical practice,breast cancer patients pay attention to bone mineral density screening and timely intervention for osteoporosis.

关 键 词：恶性肿瘤 骨质疏松 孟德尔随机化 全身骨密度 乳腺癌 

分 类 号：R730[医药卫生—肿瘤]