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饮食源性抗氧化剂与小细胞肺癌之间的遗传重叠和因果推断。

Genetic overlap and causal inferences between diet-derived antioxidants and small-cell lung cancer.

机构信息

Department of Respiratory Diseases, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.

Nursing Department, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.

出版信息

Medicine (Baltimore). 2024 Feb 23;103(8):e37206. doi: 10.1097/MD.0000000000037206.

Abstract

Several studies have reported that antioxidants exert both preventive and inhibitory effects against tumors. However, their causal effects on small-cell lung cancer (SCLC) remain controversial. Herein, we explored the causal effects of 6 antioxidants on SCLC by combining a genome-wide association study database and the Mendelian randomization (MR) approach. We obtained antioxidant genetic variance data for 6 exposure factors: carotene, vitamin A (retinol), selenium, zinc, vitamin C, and vitamin E, from the genome-wide association study database. The instrumental variables for exposure factors and SCLC outcomes were integrated by screening instrumental variables and merging data. Two-sample MR was used to analyze the causal relationship between exposure and outcomes. Finally, we examined the heterogeneity and horizontal pleiotropy of the MR analysis by performing multiple sensitivity analyses. We found a causal relationship between carotene and SCLC using two-sample MR analysis and sensitivity analysis (P = .02; odds ratio = 0.73; 95% confidence interval: 0.55-0.95). In contrast, there was no causal relationship between other examined antioxidants and SCLC. We found that diet-derived circulating antioxidants could afford protection against SCLC, and carotene is the causal protective factor against SCLC.

摘要

一些研究报道抗氧化剂对肿瘤具有预防和抑制作用。然而,它们对小细胞肺癌(SCLC)的因果效应仍存在争议。在此,我们通过结合全基因组关联研究数据库和孟德尔随机化(MR)方法,探讨了 6 种抗氧化剂对 SCLC 的因果效应。我们从全基因组关联研究数据库中获得了 6 种暴露因素(类胡萝卜素、维生素 A(视黄醇)、硒、锌、维生素 C 和维生素 E)的抗氧化剂遗传方差数据。通过筛选工具变量和合并数据,将暴露因素和 SCLC 结局的工具变量整合在一起。采用两样本 MR 分析暴露与结局之间的因果关系。最后,我们通过进行多次敏感性分析来检验 MR 分析的异质性和水平多效性。我们发现,使用两样本 MR 分析和敏感性分析,类胡萝卜素与 SCLC 之间存在因果关系(P=0.02;优势比=0.73;95%置信区间:0.55-0.95)。相比之下,其他研究的抗氧化剂与 SCLC 之间没有因果关系。我们发现,饮食来源的循环抗氧化剂可以为 SCLC 提供保护,类胡萝卜素是 SCLC 的因果保护因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9a7/11309643/691380433b4d/medi-103-e37206-g001.jpg

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