背景:越来越多的证据表明特应性皮炎(AD)可以降低肺癌(LC)的风险。然而,两种疾病之间的因果关系是不一致和有争议的。因此,我们采用孟德尔随机化(MR)方法探讨了AD与LC不同组织学亚型之间的因果关系.
方法:我们基于AD(10,788例和30,047例对照)和LC(29,266例和56,450例对照)的全基因组关联研究(GWAS)的汇总统计进行了MR研究。在去除与潜在混杂因素相关的SNP后获得仪器变量(IVs)。我们采用逆方差加权(IVW),MR-Egger,和加权中位数方法来汇集估计值,并进行了全面的敏感性分析。
结果:IVW方法的结果提示AD可降低发展为肺腺癌(LUAD)的风险(OR=0.91,95%CI:0.85-0.97,P=0.007)。此外,AD与整体LC之间无因果关系(OR=0.96,95%CI:0.91-1.01,P=0.101),肺鳞状细胞癌(LUSC)(OR=1.04,95%CI:0.96-1.036,P=0.324),小细胞肺癌(SCLC)(OR=0.95,95%CI:0.82-1.10,P=0.512)。综合灵敏度测试表明了我们结果的稳健性。
结论:本研究表明,在欧洲人群中,AD可能会降低LUAD的风险,这需要额外的研究来确定潜在的分子机制。
BACKGROUND: Growing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method.
METHODS: We conducted the MR study based on summary statistics from the genome-wide association studies (GWAS) of AD (10,788 cases and 30,047 controls) and LC (29,266 cases and 56,450 controls). Instrumental variables (IVs) were obtained after removing SNPs associated with potential confounders. We employed inverse-variance weighted (IVW), MR-Egger, and weighted median methods to pool estimates, and performed a comprehensive sensitivity analysis.
RESULTS: The results of the IVW method suggested that AD may decrease the risk of developing lung adenocarcinoma (LUAD) (OR = 0.91, 95% CI: 0.85-0.97, P = 0.007). Moreover, no causality was identified between AD and overall LC (OR = 0.96, 95% CI: 0.91-1.01, P = 0.101), lung squamous cell carcinoma (LUSC) (OR = 1.04, 95% CI: 0.96-1.036, P = 0.324), and small cell lung carcinoma (SCLC) (OR = 0.95, 95% CI: 0.82-1.10, P = 0.512). A comprehensive sensitivity test showed the robustness of our results.
CONCLUSIONS: The present study indicates that AD may decrease the risk of LUAD in the European population, which needs additional investigations to identify the potential molecular mechanisms.