Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study
Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study
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DOI：
10.1038/s41416-021-01505-8
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发表时间：
2021-07-27
影响因子：
8.8
通讯作者：
Allara, Elias
中科院分区：
文献类型：
--
作者：
Larsson, Susanna C.;Lee, Wei-Hsuan;Allara, Elias
背景皮质醇的免疫抑制、促肥胖和高血糖作用表明它可能在癌症的发生发展中发挥作用。然而，皮质醇是否会增加癌症风险尚不清楚。我们采用孟德尔随机化方法研究了血浆皮质醇与全身癌症和常见的特定部位癌症风险之间的潜在因果关系。方法以皮质醇网络联盟中3个与清晨血浆皮质醇水平相关的全基因组显着水平的遗传变异(P<；5×10(-8))作为遗传工具。癌症结果的概要水平全基因组关联研究数据来自大型癌症联盟、英国生物库和FinnGen联盟。采用固定效应逆方差加权方法进行两样本孟德尔随机化分析。使用荟萃分析将不同数据来源的估计值结合在一起。结果基因预测血浆皮质醇的标准差增加与子宫内膜癌的风险增加相关(优势比1.5，95%可信区间1.13~1.99；P=0.005)。基因预测的血浆皮质醇与其他常见的特定部位癌症，包括乳腺癌、卵巢癌、前列腺癌、结直肠癌、肺癌、恶性皮肤癌或全身癌症的风险之间没有显著的关联。结论这些结果表明，血浆皮质醇水平升高可能会增加患子宫内膜癌的风险，但不会增加其他癌症的风险。发生这种情况的机制仍有待调查。
Background Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation. Methods Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 x 10(-8)) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis. Results A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer. Conclusions These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.