According to recent studies, the incidence of early-onset cancers—often defined as those diagnosed in individuals younger than age 50—is on the rise, and not just in the United States but globally as well. Research shows that between 1990 and 2019, the global incidence of early-onset cancer increased by 79.1%, and the number of early-onset cancer deaths increased by 27.7%.
A prospective study by Tian et al presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract 846) investigated the associations between accelerated aging—in which biological age surpasses chronologic age—and the rising global incidence of early-onset cancers among recent generations. Researchers found that accelerated aging is much more common in recent birth cohorts and may emerge as a risk factor for the development of early-onset solid cancers, especially for lung, gastrointestinal, and uterine cancers. Further research to determine the mechanisms driving accelerated aging and early-onset cancers are needed to guide the development of precision cancer prevention strategies and therapeutic modalities, concluded the researchers.
Study Methodology
The researchers examined the data of 148,724 participants aged 37 to 54 in the UK Biobank database to investigate the associations between accelerated aging and the risk of early-onset solid tumor cancers diagnosed before the age of 55. Biological age was assessed using the PhenoAge algorithm based on nine blood chemistry markers collected at baseline, including albumin, alkaline phosphatase, creatinine, C-reactive protein, glucose, mean corpuscular volume, red cell distribution width, white blood cell count, and lymphocyte proportion.
Accelerated aging was quantified by standardizing the residuals of biological age after regression against chronological age. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. In secondary analyses, the researchers compared the associations with late-onset cancers diagnosed after age 55.
Results
The researchers found that across 1,707,115 person-years, 3,190 early-onset solid cancer cases occurred. They noted strong evidence showing that successive birth cohorts had incremental risk of accelerated aging, after controlling for chronologic age. Compared to those born between 1950 and 1954, individuals born in 1965 and later have a 17% higher risk of developing accelerated aging. After multivariable adjustment, accelerated aging was associated with an increased risk of early-onset solid tumors (hazard ratio [HR] per standard deviation increase [SD] = 1.08, 95% confidence interval [CI] = 1.04–1.12, P trend < .001), driven by lung (HR =. 1.42, 95% CI = 1.19–1.70), gastrointestinal (HR = 1.22, 95% CI = 1.11–1.34), and uterine (HR = 1.36, 95% CI = 1.13–1.64) cancers.
Compared with those in the lowest tertile, those in the highest tertile of accelerated aging had 2.02 times the risk for early-onset lung cancer (HR = 2.02, 95% CI = 1.13–3.62), 1.62 times the risk for gastrointestinal cancer (HR = 1.62, 95% CI = 1.27–2.08), and 1.83 times the risk for uterine cancer (HR = 1.83, 95% CI = 1.10–3.04). In contrast, the associations were weaker for late-onset lung cancer (HR per SD = 1.09, 95% CI = 0.96–1.23), gastrointestinal cancers (HR = 1.16, 95% CI = 1.08–1.24), and uterine cancer (HR = 1.23, 95% CI = 1.06–1.43).
“Accelerated aging is much more common in recent birth cohorts, and accelerated aging may emerge as a risk factor for early-onset solid cancer, especially for lung, gastrointestinal, and uterine cancers. Validation studies in diverse populations as well as mechanistic investigations are needed to further evaluate the link between accelerated aging and the pathophysiology of early-onset cancers and to guide the development of novel preventive and therapeutic modalities,” concluded the study authors.
Clinical Relevance
“By examining the relationship between accelerating aging and the risk of early-onset cancers, we provide a fresh perspective on the shared etiology of early-onset cancers,” said first study author Ruiyi Tian, MPH, a graduate student in the Division of Biology & Biomedical Sciences at Washington University School of Medicine in St. Louis. “If validated, our findings suggest that interventions to slow biological aging could be a new avenue for cancer prevention, and screening efforts tailored to younger individuals with signs of accelerated aging could help detect cancers early.”
Disclosure: Funding for this study was provided by the National Institutes of Health. For full disclosures of the study authors, visit abstractsonline.com.
