循环代谢生物标志物与东亚和欧洲人群肺癌的遗传关联。
Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans.
机构信息
Department of Thoracic Surgery, Sir Run Run Shaw Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Nursing department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
出版信息
Eur J Med Res. 2023 Apr 26;28(1):158. doi: 10.1186/s40001-023-01116-4.
BACKGROUND
Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive.
METHODS
The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) and those of the LC and its histological subtypes were retrieved from previous GWASs. We performed two-sample Mendelian randomization (MR) and multivariable MR analyses to examine the associations between genetically predicted metabolic biomarkers and LC in East Asians and Europeans.
RESULTS
In East Asians, the inverse-variance weighted (IVW) method suggests that LDL (odds ratio [OR] = 0.799, 95% CI 0.712-0.897), TC (OR = 0.713, 95% CI 0.638-0.797), and TG (OR = 0.702, 95% CI 0.613-0.804) were significantly associated with LC after correction for multiple testing. For the remaining three biomarkers, we did not detect significant association with LC by any MR method. Multivariable MR (MVMR) analysis yielded an OR of 0.958 (95% CI 0.748-1.172) for HDL, 0.839 (95% CI 0.738-0.931) for LDL, 0.942 (95% CI 0.742-1.133) for TC, 1.161 (95% CI 1.070-1.252) for TG, 1.079 (95% CI 0.851-1.219) for FPG, and 1.101 (95% CI 0.922-1.191) for HbA1c. In Europeans, the univariate MR analyses did not detect significant association between exposures and outcomes. However, in MVMR analysis integrating circulating lipids and lifestyle risk factors (smoking, alcohol drinking, and body mass index), we found that TG was positively associated with LC in Europeans (OR = 1.660, 95% CI 1.060-2.260). Subgroup and sensitivity analysis yielded similar results to the main analyses.
CONCLUSIONS
Our study provides genetic evidence that circulating levels of LDL was negatively associated with LC in East Asians, whereas TG was positively associated with LC in both populations.
背景
代谢生物标志物与肺癌（LC）风险相关。然而，来自流行病学研究的观察结果要么不一致，要么没有定论。
方法
高密度脂蛋白胆固醇（HDL）、低密度脂蛋白胆固醇（LDL）、总胆固醇（TC）、甘油三酯（TG）、空腹血糖（FPG）和糖化血红蛋白（HbA1c）的遗传汇总数据以及 LC 及其组织学亚型的遗传汇总数据，均从先前的 GWAS 中检索。我们进行了两样本 Mendelian 随机化（MR）和多变量 MR 分析，以检验东亚人和欧洲人遗传预测代谢生物标志物与 LC 之间的关联。
结果
在东亚人群中，逆方差加权（IVW）方法表明 LDL（比值比 [OR] = 0.799，95%置信区间 0.712-0.897）、TC（OR = 0.713，95%置信区间 0.638-0.797）和 TG（OR = 0.702，95%置信区间 0.613-0.804）在经过多次检验校正后与 LC 显著相关。对于其余三种生物标志物，我们没有通过任何 MR 方法检测到与 LC 的显著关联。多变量 MR（MVMR）分析得出 HDL 的 OR 为 0.958（95%置信区间 0.748-1.172），LDL 的 OR 为 0.839（95%置信区间 0.738-0.931），TC 的 OR 为 0.942（95%置信区间 0.742-1.133），TG 的 OR 为 1.161（95%置信区间 1.070-1.252），FPG 的 OR 为 1.079（95%置信区间 0.851-1.219），HbA1c 的 OR 为 1.101（95%置信区间 0.922-1.191）。在欧洲人群中，单变量 MR 分析未发现暴露与结局之间存在显著关联。然而，在整合循环脂质和生活方式危险因素（吸烟、饮酒和体重指数）的 MVMR 分析中，我们发现 TG 与欧洲人的 LC 呈正相关（OR = 1.660，95%置信区间 1.060-2.260）。亚组和敏感性分析得出的结果与主要分析相似。
结论
本研究提供了遗传证据，表明 LDL 水平与东亚人群的 LC 呈负相关，而 TG 与两个人群的 LC 呈正相关。
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