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SAN DIEGO -- Levels of aging-associated biomarkers increased significantly in people born in 1965 or later, coinciding with subsequent increases in early-onset cancers, a large prospective-cohort study showed.

As compared with people born from 1950 through 1954, individuals born in 1965 or later had a 17% higher likelihood of accelerated aging. Accelerated aging had a significant association with early-onset solid tumors, particularly lung, gastrointestinal, and uterine cancers. The data showed little association between accelerated aging and late-onset cancers.

The findings suggest accelerated aging may contribute to recent increases in early-onset cancers, defined as occurring in adults younger than 55, reported Ruiyi Tian, MPH, of Washington University in St. Louis, at the American Association for Cancer Research (AACR) annual meeting.

"Accelerated aging may emerge as a risk factor for early-onset solid cancers, especially lung, gastrointestinal, and uterine cancers," Tian said during an AACR press briefing. "These findings require validation in diverse populations. Mechanistic studies are needed to understand the association between accelerated aging and early-onset cancers. Future studies should also help guide the development of novel preventive and therapeutic modalities."

Describing the findings as "obviously very concerning information," press briefing moderator Shivaani Kummar, MD, of Oregon Health and Science University in Portland, questioned Tian about the study's limitations. Specifically, she asked whether investigators looked at the relationship between accelerated aging and other diseases, besides cancer. Kumar also wondered about factors or behaviors that might alter the results, such as smoking and tobacco cessation.

The study was limited to early-onset cancer, said Tian. Investigators adjusted for multiple confounders, including alcohol use, tobacco use, and demographic variables. With respect to lung cancer, an age-adjusted model resulted in an even stronger association with accelerated aging, which was not altered by adjustment for smoking.

"One concern is that we would like to validate the findings in more diverse populations, because right now we're using data limited to people in the U.K.," said Tian. "We would like to see this validated in other countries, other cohorts, especially in minorities, who are not normally well represented in these large population databases."

In response to another question, Tian said accelerated aging is a biological process and does not translate into a chronological number, such as 5 years older.

By way of background, Tian said interest in accelerated aging and cancer risk evolved from recent worldwide increases in early-onset cancers. From 1990 to 2019, increased substantially. The increase has been more prominent in . The increased frequency of early-onset cancers has coincided with an increased prevalence of accelerated aging, but the association between the two has not been extensively studied.

To investigate the potential link between accelerated aging and early-onset cancers, Tian and colleagues analyzed data from the , a long-term prospective study of the contributions of genetics and environmental exposures to the development of diseases. The analysis included 148,724 participants ages 37 to 54.

To calculate biological age, investigators determined baseline values of nine serum biomarkers: albumin, alkaline phosphatase, creatinine, C-reactive protein, glucose, mean corpuscular volume, red cell distribution width, white blood cell count, and lymphocyte proportion. They analyzed the biomarker values by means of the to quantify accelerated aging by birth cohort and then examined associations with early-onset cancers.

The analyses showed that people born after 1965 had a 17% increased likelihood of accelerated aging as compared with those born from 1950 through 1954. By multivariable analysis, accelerated aging was associated with a small, but significantly increased risk of early-onset cancers (HR per standard deviation 1.08, 95% CI 1.04-1.12, P<0.001). The overall result was 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.

After stratifying accelerated aging values into tertiles, investigators found that the risk of lung, gastrointestinal, and uterine cancers increased with higher aging values. Comparison of the highest and lowest tertiles resulted in the following hazard ratios:

• Lung: HR 2.02 (95% CI 1.13-3.62)
• Gastrointestinal: HR 1.62 (95% CI 1.27-2.08)
• Uterine: HR 1.83 (95% CI 1.10-3.04)

Accelerated aging had weaker associations with late-onset gastrointestinal (HR 1.16) and uterine cancers (HR 1.23), and no association with late-onset lung cancer.

"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 Tian. "If validated, our findings suggest that interventions to slow biological aging could be a new avenue for cancer prevention."

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