机构：[1]Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[2]West China School of Medicine, Sichuan University, Chengdu, China.四川大学华西医院[3]Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China.
Recent studies have observed the relationships of circulatory and dietary intake of branched-chain amino acids (BCAAs) with long-term risk of certain cancers. However, the exact causality of BCAA with lung cancer (LUCA) and its pathological subtypes remains obscure. The aim of this study is to investigate the association between BCAA metabolism and risk of LUCA.Here we conducted Mendelian randomization (MR) and observational epidemiological analyses to investigate the association between BCAA and risk of LUCA. With single nucleotide polymorphism (SNP)-phenotype association data extracted from genome-wide association studies (GWAS), we performed univariate and multivariate MR analyses to infer the causal effect of circulatory BCAA concentrations on LUCA. We further investigated the effects of several potential mediators and quantified the mediation effects. Population-level analyses were performed in the National Health and Nutrition Examination Survey (NHANES) III.Our results demonstrated that genetically predicted circulatory valine concentrations causally increased the risk of overall LUCA [odds ratio (OR) =1.324, 95% confidence interval (CI): 1.058-1.658, P=0.01]. For pathological subgroups, elevated levels of leucine, isoleucine, valine, and total BCAA were founded to be significantly associated with a higher risk of squamous cell lung cancer (LUSC); however, they did not significantly affect lung adenocarcinoma (LUAD). Moreover, body mass index (BMI) mediated approximately 3.91% (95% CI: 1.22-7.18%) of the total effect of leucine on LUSC. In the NHANES III population, dietary total BCAA intake was significantly associated with BMI ≥30 kg/m2, while no non-linear relationships were observed.This study provides genetic evidence for the histology-specific causality of BCAA on LUCA and implies the mediation role of BMI in this relationship. Further studies are needed to confirm these findings and elucidate the underlying mechanisms.2024 Journal of Thoracic Disease. All rights reserved.
基金：
This work was supported by the Key Science
and Technology Program of Sichuan Province (No.
2022YFS0158), Key Research Support Project of Chengdu
City (No. 2019-YF09-00228-SN) and Key Research Project
of Sichuan Province (No. 2022YFS0190).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|3 区医学
小类|4 区呼吸系统
最新[2023]版：
大类|3 区医学
小类|4 区呼吸系统
第一作者：
第一作者机构：[1]Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.[2]West China School of Medicine, Sichuan University, Chengdu, China.
通讯作者：
通讯机构：[1]Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.[3]Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China.[*1]Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital,Sichuan University, No. 37, Guoxue Alley, Chengdu 610041, China[*2]Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
推荐引用方式(GB/T 7714)：
Li Zongyuan,Hao Jianqi,Wang Tengyong,et al.Branched-chain amino acids and risk of lung cancer: insights from mendelian randomization and NHANES III[J].Journal Of Thoracic Disease.2024,16(8):5248-5261.doi:10.21037/jtd-24-420.
APA：
Li Zongyuan,Hao Jianqi,Wang Tengyong,Guo Chenglin&Liu Lunxu.(2024).Branched-chain amino acids and risk of lung cancer: insights from mendelian randomization and NHANES III.Journal Of Thoracic Disease,16,(8)
MLA：
Li Zongyuan,et al."Branched-chain amino acids and risk of lung cancer: insights from mendelian randomization and NHANES III".Journal Of Thoracic Disease 16..8(2024):5248-5261
