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基于临床生物标志物的生物年龄与英国生物库中癌症的风险。

Clinical biomarker-based biological aging and risk of cancer in the UK Biobank.

机构信息

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

出版信息

Br J Cancer. 2023 Jul;129(1):94-103. doi: 10.1038/s41416-023-02288-w. Epub 2023 Apr 29.

Abstract

BACKGROUND

Despite a clear link between aging and cancer, there has been inconclusive evidence on how biological age (BA) may be associated with cancer incidence.

METHODS

We studied 308,156 UK Biobank participants with no history of cancer at enrolment. Using 18 age-associated clinical biomarkers, we computed three BA measures (Klemera-Doubal method [KDM], PhenoAge, homeostatic dysregulation [HD]) and assessed their associations with incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, and melanoma) using Cox proportional-hazards models.

RESULTS

A total of 35,426 incident cancers were documented during a median follow-up of 10.9 years. Adjusting for common cancer risk factors, 1-standard deviation (SD) increment in the age-adjusted KDM (hazard ratio = 1.04, 95% confidence interval = 1.03-1.05), age-adjusted PhenoAge (1.09, 1.07-1.10), and HD (1.02, 1.01-1.03) was significantly associated with a higher risk of any cancer. All BA measures were also associated with increased risks of lung and colorectal cancers, but only PhenoAge was associated with breast cancer risk. Furthermore, we observed an inverse association between BA measures and prostate cancer, although it was attenuated after removing glycated hemoglobin and serum glucose from the BA algorithms.

CONCLUSIONS

Advanced BA quantified by clinical biomarkers is associated with increased risks of any cancer, lung cancer, and colorectal cancer.

摘要

背景

尽管衰老与癌症之间存在明确的关联,但关于生物年龄 (BA) 与癌症发病率之间的关系,仍存在不确定的证据。

方法

我们研究了 308156 名在入组时无癌症病史的英国生物库参与者。使用 18 种与年龄相关的临床生物标志物,我们计算了三种 BA 测量值(Klemera-Doubal 方法 [KDM]、PhenoAge、内稳态失调 [HD]),并使用 Cox 比例风险模型评估了它们与任何癌症以及五种常见癌症(乳腺癌、前列腺癌、肺癌、结直肠癌和黑色素瘤)发病率之间的关系。

结果

在中位随访 10.9 年期间,共记录了 35426 例新发癌症。在调整常见癌症风险因素后,年龄调整后的 KDM(危险比=1.04,95%置信区间=1.03-1.05)、年龄调整后的 PhenoAge(1.09,1.07-1.10)和 HD(1.02,1.01-1.03)每增加一个标准差,癌症发病风险显著增加。所有 BA 测量值与肺癌和结直肠癌风险增加相关,但只有 PhenoAge 与乳腺癌风险相关。此外,我们观察到 BA 测量值与前列腺癌呈负相关,但在从 BA 算法中去除糖化血红蛋白和血清葡萄糖后,这种相关性减弱。

结论

通过临床生物标志物量化的先进 BA 与癌症、肺癌和结直肠癌的发病风险增加相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d60e/10307789/36104fceabf4/41416_2023_2288_Fig1_HTML.jpg

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