Combing Through Early Data to Combat the Rise in Early-onset Cancers

Once upon a time, the United States reeked of cigarette smoke. At the postwar cigarette boom’s high-water mark, more than 40% of U.S. adults smoked. Perhaps unsurprisingly, U.S. lung cancer incidence and mortality during the 20th century reached disturbing heights, peaking at an age-adjusted 91.5 male lung cancer deaths per 100,000 U.S. residents in 1990.

But by 2023, the percentage of adult smokers hovered just over 11%, with predictably positive impact on lung cancer statistics: a mortality decline of over 47% and an incidence decline of over 31% since 2000. At a 2025 special conference of the American Association for Cancer Research (AACR), “The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities,” the story of lung cancer’s decline in the Unites States presented a striking contrast to the ongoing (and troubling) rise in early-onset cancers. Presenter Luis A. Diaz, Jr., MD, FAACR, an oncologist at the Memorial Sloan Kettering Cancer Center, said that smoking and lung cancer offer insight into one of the most challenging aspects of cancer care: changing human behavior. “Cancer research is hard. This is even harder,” Diaz, who is also an editor-in-chief of Cancer Discovery, said during the closing discussion, which he hosted alongside conference cochairs Timothy R. Rebbeck, PhD, FAACR, and AACR Past President Elizabeth M. Jaffee, PhD, FAACR. 

The decline in smoking shows that behaviors—even addictive or previously sanctioned behaviors—can be changed through messaging and policy. Addressing etiology directly, when possible, is a safe way to combat cancer, Diaz said, despite the challenges that preventing harmful exposures can present. “I have 12 doctors that see lung cancer patients at Memorial Sloan Kettering—they can’t fill their clinics,” he said during the panel, where he emphasized how strategies that directly prevent cancer, like vaccines and behavior change, demonstrably combat disease and mortality. 

In a world that has gone through industrialization and post-industrialization, toxic exposures and harmful lifestyle factors have increasingly come to dominate our environments, with general exposure to such risks increasing for members of younger birth cohorts. And as that world has become incredibly complex, our changing environments may be affecting our health faster than scientists’ ability to make definitive causal conclusions about specific factors. This conference showed that by combining more research with action that builds on emerging trends, researchers are making inroads to an actionable understanding of early-onset cancer.

Wrapped in Plastic: Microplastics’ Ubiquity and Early-onset Cancer

You have probably heard about microplastics—specifically, that they’re everywhere, with still-unclear consequences for several domains of human health (although the data are trending toward “not good”). What you might not have heard is that, of the roughly 16,000 compounds used in the production of most plastics, we only have hazard data on about 6,000 of them, according to Leonardo Trasande, MD, a professor at the New York University Grossman School of Medicine. 

During his presentation on plastics’ health effects, including their implications for early-onset cancer (a presentation that began with a concession that he is “part of the problem,” as he took a sip from a plastic water bottle), Trasande made the emphatic declaration that “we have wrapped the world in a plastic bag,” creating an environment in which plastic particles less than 5 millimeters in size are everywhere from the oceans to our food supply to our guts. Trasande cited an investigation of the growing presence of microplastics in marine life that detailed their possible health consequences, which ranged from tissue damage and inflammation to neurotoxicity and altered gene expression. He also stressed microplastics’ established presence throughout several human tissues: the placenta, carotid arterial plaque, blood, the lungs, and the testicles. 

Chemicals that leech from the plastic can break down to states that can interact with human organ systems. While we do not have sufficient data on the causative effects of microplastics on human cancers, some correlative analyses indicate potential negative effects. Patients with papillary thyroid cancer were significantly more likely than healthy individuals to have high urinary concentrations of bisphenol-A compounds (BPAs), according to one study. The flame-retardant chemicals BDE-209 and TCEP are also associated with thyroid cancer, Trasande said. 

Despite the still-emerging science on many of these plastic compounds’ impacts on cancer, Trasande warned that hormonally active chemicals in plastic like perfluoroalkyl and polyfluoroalkyl substances (PFASs) are “obesogens” associated with adiposity. And obesity is itself associated with 13 different cancers.  

In the face of a developing body of knowledge, strategies to limit our exposure to such compounds do exist at both the personal and policy levels, Trasande said. A diet of fresh foods not packaged in plastic, for example, can quickly and significantly reduce the levels of bisphenol and phthalate metabolites in the urine, according to a study of 20 participants. Another study showed that adolescent girls who scanned the labels of beauty products for phthalates, parabens, triclosan, and benzophenone-3 during a three-day period had significantly decreased concentrations of many of those compounds’ chemical markers in their urine. 

Pointing to the United Nations’ pursuit of a Global Plastics Treaty as a positive step, Trasande called for expanded research on microplastics, plastics’ constituent chemicals, and their effects on human health. “The way to solve that [research gap] that I suggest, among others, is to have something like we developed for carcinogenesis some years ago,” he said, and suggested international research cooperation for plastics and cancer. 

Abnormal Distributions: Global Disparities in Early-onset Cancer

The growing number of early-onset cancers, though possibly attributable to so-called westernization, is not limited to the Western world. Early-onset cancer incidence has always been a global cancer disparities story, said presenter Tomi Akinyemiju, PhD, a professor at the Duke Global Health Institute. 

Akinyemiju pointed to findings that showed several wide gulfs in the age groups at which some cancers are diagnosed between different countries. There is a trend of earlier onset for breast cancer and colon cancers among lower-income countries compared with higher-income countries, she noted. The age-adjusted median age at diagnosis in breast cancer cases is a full decade younger in Iran, South Korea, and Algeria (where half of breast cancer patients are initially diagnosed at age 49 or younger) than in several other countries, including the United States, Canada, and others, she said.

Investigating this uneven distribution poses problems of its own. Akinyemiju highlighted the lack of resources for comprehensive cancer registry programs in many low-income countries and the continent-wide absence of any global epidemiology cohorts within Africa (compared with the National Cancer Institute Cohort Consortium’s global 78 cohorts). That dearth of data may explain why resources like the Genome-Wide Association Studies Catalogue have so little African genetic ancestry data represented among participating individuals: just 2.03% according to a 2019 analysis. 

Early-onset cancer varies among populations within countries too, Akinyemiju said, presenting a U.S. data analysis she conducted that showed the steepest increases in early-onset colorectal cancer occurring in Hispanics from 2011 to 2022. The same analysis showed that, over time, early-onset cancer was detected at earlier stages of cancer progression in non-Hispanic white and Hispanic groups. However, this was not observed in non-Hispanic Black, non-Hispanic American Indian/Alaskan Native, or non-Hispanic Asian/Pacific Islander groups. “This suggests that early-onset cancer is not merely an artifact of better detection. If it was, you might see bigger increases across all the groups,” she said. 

Researchers can learn a lot from the people and places who have consistently experienced early-onset cancers, Akinyemiju said. By placing greater emphasis on less-researched populations—such as those in Africa, Asia, and South America—scientists can generate more holistic data to answer key questions about early-onset cancer, like which early-life exposures are the most important and which host-environment interactions drive early-onset tumors.

“What Now?”: The Future of Early-onset Cancer Research

As some of the cochairs of the conference gathered for a panel discussion to summarize the meeting’s key takeaways, Rebbeck—who is a professor at the Harvard T.H. Chan School of Public Health—addressed the problem of limited data. Because the absolute number of early-onset cancers is relatively small, he said, researchers will have to use the most rigorous statistical methods to analyze these datasets.

Jaffee, who is a professor of oncology at and the deputy director of the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, agreed. She said that, although biological studies of correlated risk factors are necessary for early-onset cancer research, studying every correlate at such a level of detail just wouldn’t be feasible. The best use of data and resources for early-onset cancer research, the panelists concurred, would prioritize biological studies of risk factors with strong associations in multiple cohorts. What scientists needed more than anything, Rebbeck said, was more research. But that research will necessarily be conducted in the future—while people are presenting with more early-onset cancers in the present. 

Concluding the conference, panelists and participants alike noted a distinctive atmosphere of curiosity and enthusiasm for the topic of early-onset cancers. “This is a unique meeting for the AACR, and I think it’s been fantastic—a very diverse group of expertise,” Diaz said hopefully. “I think everyone’s going to go home with new ideas and new hypotheses.”