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儿童晒伤次数对黑色素瘤的因果效应:一项单变量和多变量孟德尔随机化研究。

The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study.

作者信息

Sun Wei, Sun Huihui, Yu Chong

机构信息

Department of Radiation Oncology, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, 213000, China.

Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.

出版信息

Open Med (Wars). 2024 Nov 29;19(1):20241078. doi: 10.1515/med-2024-1078. eCollection 2024.

Abstract

Observational studies have shown an association between childhood sunburn occasions (CSOs) and melanoma (MIS). However, these studies have shown contradictory results. Here, we used a two-sample Mendelian randomization (MR) method to make a causal inference between CSOs and melanoma at the genetic level. Based on the publicly available genome-wide association study summary data, including childhood sunburn ( = 346,955) and MIS ( = 218,792), the inverse-variance weighted (IVW) method of the random effects model was used, supplemented by the MR-Egger method, the weighted median method, and the weighted mode method. IVW results showed a 2.58-fold increased risk of melanoma development for each standard deviation increase in CSOs (odds ratio [OR] = 3.58; 95% confidence interval [CI]: 1.68-7.64; = 1.00 × 10), with the MR-Egger (OR = 4.76, 95% CI: 1.65-13.75, = 5.60 × 10), weighted median (OR = 4.89, 95% CI: 1.62-14.76, = 4.90 × 10), and weighted mode (OR = 6.26, 95% CI: 2.49-15.77, = 3.00 × 10) supporting the results. Furthermore, both the funnel plot and the MR-Egger intercepts showed the absence of directional pleiotropy between childhood sunburn and MIS. Our study confirmed that CSOs increase the risk of melanoma development.

摘要

观察性研究表明儿童晒伤次数(CSOs)与黑色素瘤(MIS)之间存在关联。然而,这些研究结果相互矛盾。在此,我们使用两样本孟德尔随机化(MR)方法在基因水平上对CSOs与黑色素瘤之间进行因果推断。基于公开可用的全基因组关联研究汇总数据,包括儿童晒伤(n = 346,955)和MIS(n = 218,792),采用随机效应模型的逆方差加权(IVW)方法,并辅以MR-Egger方法、加权中位数方法和加权模式方法。IVW结果显示,CSOs每增加一个标准差,黑色素瘤发生风险增加2.58倍(优势比[OR]=3.58;95%置信区间[CI]:1.68 - 7.64;P = 1.00×10⁻⁴),MR-Egger方法(OR = 4.76,95%CI:1.65 - 13.75,P = 5.60×10⁻³)、加权中位数方法(OR = 4.89,95%CI:1.62 - 14.76,P = 4.90×10⁻³)和加权模式方法(OR = 6.26,95%CI:2.49 - 15.77,P = 3.00×10⁻³)均支持该结果。此外,漏斗图和MR-Egger截距均显示儿童晒伤与MIS之间不存在方向性多效性。我们的研究证实CSOs会增加黑色素瘤发生的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/077d/11627034/d75e31d5dfe8/j_med-2024-1078-fig001.jpg

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