背景:报告表明,脂质分布可能与发生皮肤癌的可能性有关,然而确切的因果关系仍然未知。
目的:本研究旨在研究脂质组与皮肤癌之间的联系,以及调查任何可能的调解员。
方法:根据全基因组关联研究(GWAS),对179个脂质粒和每种皮肤癌进行了双样本孟德尔随机化(MR)分析,包括黑色素瘤,基底细胞癌(BCC),鳞状细胞癌(SCC)。然后,进行贝叶斯加权MR以验证双样本MR的分析结果。此外,我们采用两步MR研究了TNF样弱凋亡诱导因子(TWEAK)介导的脂质对皮肤癌发病率的影响.
结果:MR分析确定遗传预测较高的磷脂酰胆碱(PC)(17:0_18:2)可以降低皮肤肿瘤的风险,包括BCC(OR=0.9149,95%CI:0.8667-0.9658),SCC(OR=0.9343,95%CI:0.9087-0.9606)和黑色素瘤(OR=0.9982,95%CI:0.9966-0.9997)。通过TWEAK介导的遗传预测预测的PC(17:0_18:2)的比例在BCC中为6.6%,在SCC中为7.6%。PC(17:0_18:2)与黑色素瘤之间的因果关系不是由TWEAK介导的。
结论:这项研究确定了PC(17:0_18:2)和角质形成细胞癌之间的负因果关系,其中一小部分是由TWEAK介导的,其余大多数中介因素仍不清楚。未来还需要进一步研究其他风险因素。
BACKGROUND: Reports suggest that lipid profiles may be linked to the likelihood of developing skin cancer, yet the exact causal relationship is still unknown.
OBJECTIVE: This study aimed to examine the connection between lipidome and skin cancers, as well as investigate any possible mediators.
METHODS: A two-sample Mendelian randomization (MR) analysis was conducted on 179 lipidomes and each skin cancer based on a genome-wide association study (GWAS), including
melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Then, Bayesian weighted MR was performed to verify the analysis results of two-sample MR. Moreover, a two-step MR was employed to investigate the impact of TNF-like weak inducer of apoptosis (TWEAK)-mediated lipidome on skin cancer rates.
RESULTS: MR analysis identified higher genetically predicted phosphatidylcholine (PC) (17:0_18:2) could reduce the risk of skin tumors, including BCC (OR = 0.9149, 95% CI: 0.8667-0.9658), SCC (OR = 0.9343, 95% CI: 0.9087-0.9606) and
melanoma (OR = 0.9982, 95% CI: 0.9966-0.9997). The proportion of PC (17:0_18:2) predicted by TWEAK-mediated genetic prediction was 6.6 % in BCC and 7.6% in SCC. The causal relationship between PC (17:0_18:2) and
melanoma was not mediated by TWEAK.
CONCLUSIONS: This study identified a negative causal relationship between PC (17:0_18:2) and keratinocyte carcinomas, a small part of which was mediated by TWEAK, and most of the remaining mediating factors are still unclear. Further research on other risk factors is needed in the future.