Measures of Biological Age Largely Correlate with Cancer Risk
Cancer is an age-related condition. With age, there is a greater background of mutational damage that spreads throughout tissues. Greater inflammatory, pro-growth signaling by lingering senescent cells makes the environment more hospitable for cancerous growth once it is underway. The aging immune system becomes ever less able to destroy precancerous and cancerous cells rapidly enough to stop a cancer in its earliest stages.
Thus we should expect people who show an accelerated biological age to exhibit a greater risk of cancer, and this is largely the case. Most measures of biological age have quirks, however, as they are based on metrics that most likely only strongly reflect one or a few of the underlying mechanisms of aging, not all of them. Thus we might also expect to find that some measures of biological age do not correlate well with the risk of some specific cancers.
We studied 308,156 UK Biobank participants with no history of cancer at enrollment. Using 18 age-associated clinical biomarkers, we computed three biological age 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.
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), age-adjusted PhenoAge (hazard ratio = 1.09), and HD (hazard ratio = 1.02) was significantly associated with a higher risk of any cancer. All biological age 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 biological age measures and prostate cancer, although it was attenuated after removing glycated hemoglobin and serum glucose from the biological age algorithms.