Department of Respiratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210046, China.
Nutrients. 2022 Oct 31;14(21):4569. doi: 10.3390/nu14214569.
Previous observational studies have suggested that the effect of diet-derived circulating micronutrient concentrations on lung cancer (LC) risk is controversial. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between circulating micronutrient concentrations and the overall risk of LC and three LC subtypes (namely lung adenocarcinoma (LA), squamous cell lung cancer (SqCLC), and small cell lung cancer (SCLC)). The instrumental variables (IVs) of 11 micronutrients (beta-carotene, calcium, copper, folate, lycopene, magnesium, phosphorus, retinol, selenium, zinc, and vitamin B6) were screened from the published genome-wide association studies (GWAS). Summary statistics related to LC and its subtypes came from the largest meta-analysis, including 29,266 cases and 56,450 controls. Inverse-variance weighted (IVW) method is used as the main MR analysis, and the sensitivity analysis is carried out to ensure the MR assumptions. This MR study found suggestive evidence that genetically predicted 6 circulating micronutrient concentrations was correlated with the risk of overall LC (odds ratio (OR): 1.394, 95% confidence interval (CI): 1.041-1.868, = 0.026, phosphorus), LA (OR: 0.794, 95% CI: 0.634-0.995, = 0.045, beta-carotene; OR: 0.687, 95%CI: 0.494-0.957, = 0.026, calcium), SqCLC (OR: 0.354, 95% CI: 0.145-0.865, = 0.023, retinol), and SCLC (OR: 1.267, 95% CI: 1.040-1.543, = 0.019, copper; OR: 0.801, 95% CI: 0.679-0.944, = 0.008, zinc). We found no evidence that other micronutrients are associated with the risk of overall LC or its subtypes. Our study suggested that the increase in circulating beta-carotene, calcium, retinol, and zinc concentration may reduce the risk of LC; the increase in circulating copper and phosphorus concentration may be related to the increased risk of LC. In the future, larger replication samples of LC genetic data and larger micronutrient-related GWAS will be needed to verify our findings.
先前的观察性研究表明,饮食来源的循环微量营养素浓度对肺癌(LC)风险的影响存在争议。我们进行了两样本孟德尔随机化(MR)分析,以调查循环微量营养素浓度与整体 LC 风险和三种 LC 亚型(肺腺癌(LA)、鳞状细胞肺癌(SqCLC)和小细胞肺癌(SCLC))之间的因果关系。从已发表的全基因组关联研究(GWAS)中筛选出 11 种微量营养素(β-胡萝卜素、钙、铜、叶酸、番茄红素、镁、磷、视黄醇、硒、锌和维生素 B6)的工具变量(IVs)。与 LC 及其亚型相关的汇总统计数据来自最大的荟萃分析,包括 29266 例病例和 56450 例对照。逆方差加权(IVW)法作为主要的 MR 分析方法,并进行敏感性分析以确保 MR 假设成立。这项 MR 研究发现,遗传预测的 6 种循环微量营养素浓度与整体 LC 风险相关(比值比(OR):1.394,95%置信区间(CI):1.041-1.868, = 0.026,磷)、LA(OR:0.794,95%CI:0.634-0.995, = 0.045,β-胡萝卜素;OR:0.687,95%CI:0.494-0.957, = 0.026,钙)、SqCLC(OR:0.354,95%CI:0.145-0.865, = 0.023,视黄醇)和 SCLC(OR:1.267,95%CI:1.040-1.543, = 0.019,铜;OR:0.801,95%CI:0.679-0.944, = 0.008,锌)。我们没有发现其他微量营养素与整体 LC 或其亚型的风险相关的证据。我们的研究表明,循环β-胡萝卜素、钙、视黄醇和锌浓度的增加可能降低 LC 风险;循环铜和磷浓度的增加可能与 LC 风险增加有关。未来,需要更大的 LC 遗传数据和更大的与微量营养素相关的 GWAS 复制样本来验证我们的发现。