Cancer has been recognized as an environmental disease since the first description of chimney sweep’s cancer by Percivall Pott in 1775. The primary social determinant of this disease is described well in this article Lancet Oncology (Abstract then unfortunately a paywall), even if the “social determinants of health” are anathema during our MAHA Moment. More recently, smoking and asbestos and other chemical exposures have been convincingly shown to be environmental causes of cancer. Cancer Alley is on the Mississippi River between Baton Rouge and New Orleans and downstream to the Gulf of Mexico for a reason: The exposome [1] of oil and chemical workers and their families, however strenuously the Merchants of Doubt dispute the claims of those harmed. It is not an accident these merchants are much more likely to live in bucolic Great Barrington than Cancer Alley or any other of thousands of industrial sacrifice zones around the world.
Research beginning in the 1960s has elucidated the molecular and cellular bases of cancer. The Ames Test identified mutagenic compounds and showed that carcinogens are often not mutagenic until they are acted upon by liver enzymes (e.g., cytochrome p450s) and converted into reactive compounds that damage DNA. For example, benzo(a)pyrene and similar polycyclic aromatic hydrocarbons (PAHs) found in incomplete combustion products in chimney soot, tobacco smoke, and grilled food are not mutagenic but their reactive metabolic products produced as the body tries to eliminate them are and will damage DNA. The downstream effects of mutagenesis in cancer progression are now well understood and have shown that cancer is nearly always a long, multistep process.
Thus, cancer has been called a late-onset disease of aging. The common argument is that if you live long enough, you will get cancer. But a number of cancers are now frequently diagnosed earlier than expected, and this has led to some rethinking of the nature of oncogenesis and cancer progression. Several research groups have asked the question, “If cancer is appearing in younger people, is this because they are aging faster?” This is not a simple question and will probably never yield a simple answer, but results published online on 22 June 2026 by Yin Cao and her research group at Washington University in St. Louis are suggestive: Tian et al., Biological aging and generational shifts in early-onset cancer risk (open access):
Over the past three decades, early-onset cancers, diagnosed in adults often under age 50 or 55 years, have become a global cancer prevention and public health challenge. Between 1990 and 2019, cancers diagnosed under the age of 50 years increased by 24% globally and continue to rise. In the United States (US), this increasing trend is led by several cancers, including multiple myeloma, colorectal cancer and uterine cancer. Notably, this upward trend is more pronounced in recent generations compared to earlier ones in many countries. In Australia, Canada, the United Kingdom (UK) and the US, people born in the 1990s face at least a fourfold higher risk of early-onset colorectal cancer compared with those born in the 1960s. In the US, compared with people born before 1950, those born circa 1985 have approximately twice the risk of uterine cancer. Moreover, cohorts with elevated incidence before age 50 years seem to carry this excess risk into ages 50–54 years. In the US, the proportion of colorectal cancers diagnosed before age 55 increased from 11% in 1995 to 20% in 2019, and in the UK, incidence among adults aged 50–54 years rose by 0.58% annually between 2008 and 2017. Together, these patterns suggest the influence of emerging generational risk factors. (emphasis added here and below)
…
A wide array of physiological and environmental factors can converge on aging-related processes, including chronic inflammation, cumulative genetic damage, epigenetic changes, alterations in the tissue microenvironment, and dysregulation of adaptive and innate immunity, all of which have been linked to processes involved in tumor initiation and progression. These processes can reinforce one another, reshaping both systemic and organ-specific tissue contexts and increasing susceptibility to malignant transformation, ultimately accelerating cancer onset at younger ages. Furthermore, given that people’s aging trajectories may vary across organ systems and diverge from systemic aging of the whole body, organ-specific aging may influence early-onset cancer risk either independently or in concert with systemic aging.
This research uses a metric called PhenoAge, which is the result of a multicomponent calculation of biological age. Individuals with a PhenoAge older than their chronological age are biologically older than the calendar says they should be. Consequently, if they are biologically older, then their risk of cancer is increased. Markers used to calculate PhenoAge include nine clinical biochemistry markers. The similar Klemera-Doubal method (KDM, well accepted in the molecular geriatrics) uses eight clinical biochemistry markers and two anthropometric measures. Changes in metabolic flux (metabolomics) is used as a correlate of chronological age and the analysis of protein composition (proteomics) serves as a proxy for organ-specific aging. Sydney Brenner, boon companion of Francis Crick, famously derided “-omic biology” in its early days but he missed on that one, even if the term has been stretched far beyond the original “genomic.”
An overview of the study design is presented in Figure 1. For our purposes, this will be considered something of a black box that yields interesting data that may begin to answer the question of whether younger people who get cancer are biologically older than they should be. The other possibility, of course, is that these younger people are older than they should be on the cancer progression timescale because they have been exposed to a larger burden of cancer-causing insults than those who came before them. The latter probably has more explanatory power.
Crucial to the validity of this study is the size of the sample. The UK Biobank contains records of 154,169 subjects. The All of Us Research Program of the United States includes 10,262 subjects. [2] So, to a first approximation, the sample size is large enough to provide provisional answers in this approach to molecular epidemiology. The data are convincing, as far as they go, but as the authors state, there is much more going on here than accelerated aging:
Although our overall findings are in line with previous work linking a greater age gap to cancer risk in older adults, evaluating this association earlier in the life-course is both biologically grounded and, if validated, provides a complementary approach in addressing the principal challenges in early-onset cancer etiology: fully enumerating all contributing exposures is difficult…Our findings suggested that age gap may be particularly relevant for understanding early-onset cancers with rising incidence, such as colorectal and uterine cancers, as well as for cancers with substantial unexplained risk, such as lung cancer. In the UK, 67% of young lung cancer patients are diagnosed at stage IV, and in the US, the incidence of early-onset lung cancer is now higher among women, who are mostly never-smokers. Finally, our analyses showed the associations between age gap and early-onset lung, GI and uterine cancers are independent of telomere length, a known marker of biological age, genetic predisposition of aging as well as cancer, suggesting age gap captures risk beyond canonical and inherited aging pathways and motivating additional mechanistic studies.
These mechanistic studies will necessarily include matters we discussed here in January 2025 regarding early-onset cancers, particularly colorectal cancer. The most likely causes of this increase in early-onset cancers are several factors mentioned above, including chronic inflammation due to obesity and the increasingly sedentary lifeways of the Global North. That the increased incidence of early-onset cancers has occurred more or less concomitantly with changes in the Western diet in which fat calories and cholesterol were demonized and replaced with refined carbohydrates (sugar) and, yes, ultraprocessed foods, implies a systemic if not simple cause for these changes in generational cancer burden.
This brings up a potential problem with this approach to accelerated biological aging as the cause of generational shifts in early-onset cancer risk. In the gloss from WUSTL about this research Dr. Cao is quoted:
Our ultimate goal is to decode how modern environments become biologically embedded to drive cancer risk, transforming prevention from broad recommendation to personalized interventions…If we can identify younger people with the highest cancer risk when they are still healthy, we can focus on prevention and early-detection strategies for individuals who will benefit most from early interventions.”
Not necessarily. Personalized interventions cannot solve a systemic population problem, but they are all the rage now, especially in the world of MAHA health influencers, and this is where notions like PhenoAge [3] and the like are common. At Pheno, for example, you will find “A data-driven, holistic platform that empowers employees to take control of their health, while enabling companies to foster a healthier, more productive workforce.” Maybe, but someone else will have to fill out that contact form.
This does not mean, however, that accelerated biological aging, depending on how this is defined and measured, is not an important part of the explanation of early-onset cancers. Biological aging and generational shifts in early-onset cancer risk does not overinterpret and it is well grounded in what is known about cancer onset and progression.
This is a subject too important to ignore. We do not assign homework here, but the following papers (all open access) from the bibliography of Tian et al. are very well written and especially well illustrated. They can be used to dive as deep as you want into this current literature.
Embracing cancer complexity: Hallmarks of systemic disease (2024). The authors are a well-established cancer researchers. This paper covers virtually all of cancer biology
Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers (2026). The corresponding author is Lin Cao of WUSTL and places the paper discussed above in context.
Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems (2025) This paper represents a proof-of-principle for organ-specific aging in the study design of the paper discussed above.
Increase of early-onset colorectal cancer: a cohort effect (2026). This paper also places early-onset cancers in context:
All countries showed increasing early-onset colorectal cancer incidence in successive birth cohorts since 1960, with individuals born in the 1990s facing at least 4-fold higher risks than individuals born in the 1960s. Cohort effects were observed across all countries, with sharper increases at younger ages. Over the most recent decade, the estimated annual percentage change ranged from 3.4% in Australia and the United States to 4.5% in England, with steep rises before age 40 years. The emergence of these trends from ages 20 to 29 years suggests that contributing factors may originate early in life and reflect exposures whose effect begin in youth and accumulate throughout the lifespan.
This accumulation of early insults/exposures that lead to colorectal cancer are undoubtedly systemic and unavoidable in most of the affected populations of Australia, Canada, England, and the United States. Identifying and preventing them may require as much time as it has taken for them to appear.
Interpretation: 17 of 34 cancers had an increasing incidence in younger birth cohorts, including nine that previously had declining incidence in older birth cohorts. These findings add to growing evidence of increased cancer risk in younger generations, highlighting the need to identify and tackle underlying risk factors.
Yes, something very real is happening, not unlike the current heat wave in Europe and the trickling future of the Colorado River, and it is undoubtedly environmental. The question is whether we will pay close enough attention to do anything about it, something we as a people seem to have forgotten how to do.
Notes
[1] This paper is the earliest description/definition of exposome I could find: “The potential interactions between genome and exposome are certainly real if difficult to parse: The imbalance in measurement precision of genes and environment has consequences, most fundamentally in compromising the ability to fully derive public health benefits from expenditure on the human genome and the aforementioned cohort studies. There is a desperate need to develop methods with the same precision for an individual’s environmental exposure as we have for the individual’s genome. I would like to suggest that there is need for an “exposome” to match the “genome.” This concept of an exposome may be useful in drawing attention to the need for methodologic developments in exposure assessment.” When I think of my exposome as a heavy chemical worker, I shudder at the number of exposures I experienced.
[2] This is what you get when one country has had a universal National Health Service and the other consists of a hopeless patchwork of systems that make up a very large non-service health care sector of the for-profit economy. Which reminds one of Aneurin Bevan, who established the NHS in the British Labour Government immediately after WWII: “The field in which the claims of individual commercialism come into most immediate conflict with reputable notions of social values is that of health.” One might also add big business, public-private partnership (sic) commercialism, but Nye Bevan, from the Welsh coal country, worked long before Margaret Thatcher pronounced “There is no alternative” while utterly destroying British industry. Although Bevan was Old Labour through and through, our current Neoliberal Dispensation was probably unimaginable to him.
[3] Perhaps an easy way to grasp PhenoAge is to compare phenotype versus genotype in biology. We cannot “see” the genotype. But we can see phenotype (blonde hair, blue eyes, green peas, calico coat). In this case the age we can see in the subjects of the study comes from what can be measured, not from the birthdate. (OED: phen-, pheno- Greek: shining, to bring light, cause to appear, show)
