Why are more young people developing cancer? A major new study suggests that accelerated biological aging may be fueling the rise in cancers diagnosed in people under the age of 55, providing new clues to one of medicine’s fastest-growing mysteries.
Research: Biological aging and generational alternation in early cancer risk. Image credit: Ground Picture/Shutterstock.com
New research published in natural medicine Association between accelerated biological aging and early cancer risk in young people.
Biological age emerges as a cancer risk marker
The incidence of young-onset cancers diagnosed in adults younger than 55 years has increased significantly over the past 30 years, with a 24% increase reported worldwide between 1990 and 2019. This increase in prevalence is more pronounced in younger than older generations in many countries, including Australia, Canada, the United States, and the United Kingdom. This trend highlights the emergence of generational risk factors that need to be deciphered.
Complementary strategies that integrate cumulative exposure to risk factors and capture biology common to multiple cancers may be effective in understanding how generational risk factors influence cancer development. In this context, aging, which reflects the overall impact of exposure and correlates with several cancer characteristics, could serve as a potential measure.
Several physiological and environmental factors play a central role in age-related changes, including chronic inflammation, genetic damage, epigenetic changes, and immune dysfunction. These changes are also substantially associated with malignant transformation and progression. It is well known that older people are at higher risk of developing cancer because their bodies have had more time to accumulate these changes that ultimately lead to malignant transformation.
Given the increasing incidence of cancer in young people, researchers at Washington University School of Medicine in St. Louis conducted an observational cohort study to investigate whether these age-related changes accumulate faster in younger people and are associated with increased cancer risk later in life. The study included 154,169 young people from the UK Biobank and 10,262 participants from the All of Us Research Program in the US.
The researchers applied a statistical algorithm that uses metabolite-derived age scores and standardized clinical biomarkers to measure biological aging. They used these methods to estimate whole-body aging, which reflects a progressive systemic decline in physiological processes across multiple organ systems.
For organ-specific aging, we used blood proteomics data that provides levels of multiple proteins associated with specific organ systems. They calculated the gap between each birth cohort’s biological age (the progressive decline in physiological function over time) and chronological age (the number of years a person has lived since birth) and used the standard deviation to assess how different each group was from the study average.
Greater biological age difference predicts cancer risk
An analysis of UK Biobank participants found that people born between 1965 and 1974 were 23% more likely to experience systemic aging than those born between 1950 and 1954. This increase in systemic aging was associated with an 8% higher risk of early-onset cancers, particularly lung, gastrointestinal, and uterine cancers. These associations remained even after further adjustment for leukocyte telomere length and genetic predisposition to aging and cancer.
When UK Biobank participants were categorized based on the state of systemic aging, researchers found that those with the highest systemic aging had a 15% higher risk of developing early cancer.
Similar systemic aging trends were observed in the US cohort. Participants born between 1990 and 1999 had 92% of one standard deviation more aging overall than participants born between 1965 and 1969. Partial validation of the findings was obtained in the US cohort, but site-specific analyzes were limited by the small number of cancer cases and short follow-up.
Analysis of organ-specific aging reveals that accelerated aging of the immune system and adipose tissue (adipose tissue) are associated with increased risk of early-onset lung and colorectal cancer, respectively.
Biological aging may help identify high-risk adults
the study They found that more recent generations showed a larger biological age difference than previous generations, and that this larger age difference was associated with a higher risk of developing cancers diagnosed between the ages of 18 and 55.
The study also reveals that the larger the gap between biological and chronological aging, the higher the risk of early cancer development. In light of these findings, the researchers suggest that, if validated in future studies, assessing measures of biological aging and age differences may serve as an effective strategy for identifying individuals at increased risk of developing cancer at a relatively young age, which in turn may help inform prevention and early detection strategies.
Researchers around the world are currently investigating potential environmental, lifestyle, and social risk factors and mechanisms that may contribute to accelerated aging and associated cancer risk in young people. These global efforts are being led in part by researchers at the Siteman Cancer Center, based at Barnes-Jewish Hospital in St. Louis and Washington University School of Medicine, and by researchers at Cancer Grand Challenge, a global initiative co-founded by the National Cancer Institute and Cancer Research UK.
Because of limited sample size, researchers were unable to perform site-specific analyzes for many cancer types in the U.S. cohort. Furthermore, organ-specific aging analyzes have only been performed in a subset of UK Biobank participants, and the results require independent validation in larger cohorts. Furthermore, the study also included participants from the United Kingdom and the United States, limiting the generalizability of the findings to populations in other countries with different demographic, socio-economic, environmental, and medical characteristics.
Because this study is observational and relies primarily on single-time point estimates of biological aging, it cannot determine whether accelerated biological aging directly causes early-onset cancer.
Given these limitations, the researchers emphasize the need for future studies with larger sample sizes to validate their findings with longitudinal aging measurements, ideally using both systemic and organ-specific approaches.
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