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 × 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.

中文翻译：

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评估皮质醇在癌症中的作用：一项广泛的孟德尔随机研究

背景

皮质醇的免疫抑制、致肥胖和高血糖作用表明它可能在癌症发展中发挥作用。然而，皮质醇是否会增加癌症风险尚不清楚。我们使用孟德尔随机化研究了血浆皮质醇与整体和常见部位特异性癌症风险之间的潜在因果关系。

方法

在皮质醇网络联盟中，在全基因组显着性水平 ( P  < 5 × 10 ^-8 ) 与早晨血浆皮质醇水平相关的三个遗传变异被用作遗传工具。癌症结果的摘要级全基因组关联研究数据来自大型癌症联盟、英国生物银行和 FinnGen 联盟。使用固定效应逆方差加权法进行两样本孟德尔随机化分析。使用荟萃分析将跨数据源的估计值结合起来。

结果

遗传预测血浆皮质醇的标准差增加与子宫内膜癌风险增加相关（优势比 1.50，95% 置信区间 1.13-1.99；P  = 0.005）。基因预测的血浆皮质醇与其他常见部位特异性癌症的风险之间没有显着关联，包括乳腺癌、卵巢癌、前列腺癌、结直肠癌、肺癌或恶性皮肤癌或整体癌症。

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研究。