Why are more young adults developing cancer? A major new study suggests that accelerated biological aging may be helping fuel the rise in cancers diagnosed before age 55, offering a new clue to one of medicine’s fastest-growing mysteries.
Study: Biological aging and generational shifts in early-onset cancer risk. Image credit: Ground Picture/Shutterstock.com
A new study published in Nature Medicine links faster biological aging with early-onset cancer risk in younger generations.
Biological age emerges as a cancer risk marker
The prevalence of early-onset cancers, diagnosed in adults aged less than 55 years, has increased significantly over the past three decades, with 24% increase reported between 1990 and 2019 worldwide. This increasing prevalence is more pronounced among 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 decoded.
A complementary strategy that integrates cumulative exposure to risk factors and captures shared biology across multiple cancers could be effective for understanding how generational risk factors influence cancer onset. In this context, aging, which reflects the summated impact of exposures and interconnects with several cancer hallmarks, may serve as a potential measure.
Several physiological and environmental factors play a central role in age-related changes, including chronic inflammation, genetic damage, epigenetic alterations, and immune dysfunction. These changes are also substantially associated with malignant transformation and progression. It is well-known that older adults are at higher risk of developing cancer as they have had more time accumulating these changes in the body that eventually trigger malignant transformation.
Given the increasing prevalence of cancer in younger generations, researchers at Washington University School of Medicine in St. Louis conducted an observational cohort study to investigate whether these age-related changes are accumulating faster in younger adults and subsequently are associated with an increased risk of cancer. The study included 154,169 young adults from the UK Biobank and 10,262 participants from the United States All of Us Research Program.
The researchers applied a metabolite-derived age score and statistical algorithms that measure biological aging using standardized clinical biomarkers. They used these methods to estimate systemic aging, which reflects the progressive, whole-body decline in physiological processes across multiple organ systems.
For organ-specific aging, they used blood proteomic data, which provides levels of multiple proteins linked to specific organ systems. They calculated the gap between biological age (the progressive decline in physiological functions over time) and chronological age (the number of years a person has lived since birth) for each birth cohort and used standard deviation to assess how much each group differed from the study average.
Larger biological age gaps predict cancer risk
The analysis involving participants from the UK Biobank revealed that those born between 1965 and 1974 have 23% of one standard deviation higher systemic aging than their counterparts born between 1950 and 1954. This increased systemic aging was associated with 8% higher risk of early-onset cancer, particularly lung, gastrointestinal, and uterine cancers. These associations remained similar after additional adjustment for leukocyte telomere length and inherited genetic predisposition to aging or cancer.
The categorization of UK Biobank participants based on their systemic aging status revealed that those with the highest level of systemic aging have 15% higher risk of early-onset cancers.
In the US cohort, a similar trend of systemic aging was observed. Participants born between 1990 and 1999 had 92% of one standard deviation higher systemic aging than their counterparts born between 1965 and 1969. The US cohort provided partial validation of the findings, although the smaller number of cancer cases and shorter follow-up limited site-specific analyses.
The analysis of organ-specific aging revealed that accelerated aging of the immune system and adipose tissue (fat tissue) are associated with increased risks of early-onset lung and colorectal cancers, respectively.
Biological aging may help identify high-risk adults
The study found that more recent generations exhibited greater biological age gaps than earlier generations and that this greater age gap is associated with a higher risk of developing cancers diagnosed between ages 18 and 55 years.
The study also reveals that the larger the gap between biological and chronological aging, the higher the risk of early-onset cancer. Given these findings, the researchers suggest that, if validated in future studies, assessment of biological aging and age-gap measures could serve as an effective strategy to identify individuals at higher risk of developing cancer at a relatively young age, which in turn could help inform preventive and early-detection strategies.
Researchers around the world are currently exploring potential environmental, lifestyle, and societal risk factors and mechanisms that may contribute to accelerated aging and related cancer risk in younger generations. Some of these global efforts are led by researchers of Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, and Cancer Grand Challenges, a global initiative co-founded by the National Cancer Institute and Cancer Research U.K.
Because of the limited sample size, the researchers could not conduct site-specific analyses for many cancer types in the US cohort. Furthermore, organ-specific aging analyses were conducted only in a subset of UK Biobank participants, and the findings require independent validation in larger cohorts. In addition, the study included participants from the UK and the US, which limits the generalizability of its findings to populations in other countries with different demographic, socioeconomic, environmental, and healthcare characteristics.
As the study was observational and relied largely 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 highlight the need for validation of their findings in future studies with larger sample sizes and, ideally, longitudinal aging measurements using both systemic and organ-specific approaches.
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