Q&A: Investigating the Emerging Epidemic of Early-Onset Cancer

Over the past few decades, early-onset cancer, or cancer diagnosed in adults younger than 50 years of age, has steadily increased. Shuji Ogino, MD, PhD, chief of the Molecular Pathological Epidemiology Program in the Department of Pathology at Brigham and Women’s Hospital, is a leader in early-onset cancer research examining the cause and future implications.

Ogino established the Molecular Pathological Epidemiology (MPE) discipline, which integrates the science of molecular pathology and epidemiology to examine the connection between the patient, environmental factors (including lifestyle, dietary and microbial differences) and the disease process at the molecular, cellular, tissue, individual and population levels.

Ogino joined the Brigham in 2001 and is a professor both in pathology at Harvard Medical School and in epidemiology at the Harvard T.H. Chan School of Public Health. He has published numerous original research articles exploring risk factors, prevention, and treatment of early-onset cancers.

Your research on an emerging epidemic of early-onset cancer has received national and international attention. What patterns have you and your colleagues detected and what hypotheses may explain these rising rates?

In the early 2010s, we observed a steady increase in early-onset colorectal cancer incidence that’s been occurring since the 1990s. Initially, it wasn’t too obvious, but in the mid 2010s, it became increasingly so. In 2020, we recognized that it was not just colorectal but other early onset cancer types that were increasing. The trend is real, and there’s no sign of plateauing.

We observed that people born in later (successive) generations have a higher risk of early-onset cancer, such as early-onset colorectal cancer and other cancer types.  

For example, someone who is 40 now, meaning born in 1984, has a higher risk compared to a person born in 1974 who was 40 in 2014. We need to compare the risk of cancer at the same age, 40 years old in this example. We observe that a person born in later years has higher early-onset cancer risk at a given age.   

This suggests risk factor exposures started at an earlier age.  

What prompted your interest in researching early-onset cancer?

There is more aggressive cancer happening earlier, in younger people, and I think we have to know why. We have to know what the risk factors are and how we can prevent this. Molecular pathological epidemiology research can certainly contribute to this area. Also, we have to increase awareness so that people can go to the doctor before it’s too late. Young people who are 30 or 40 don’t think of getting cancer. They might think they are too young to get cancer and delay going to the doctor until it becomes very difficult to treat.

What is the relationship between cancer and the gut microbiome?

That’s still a big question. There are recent studies published by other groups linking early-onset colorectal cancer to the specific mutational signature caused by the bacterial toxin colibactin, which is produced by what we call pks+ E. coli. Colibactin is a genotoxin, meaning it damages DNA in the cell. We see that type of signature more in early-onset cancer. We published a study that the western diet has been associated with increased incidence of colorectal cancer having pks+ E. coli. So we started to see an indirect link, not a direct link yet, between the western diet and early-onset colorectal cancer. The western diet is high in red meat, processed meat, animal fat, refined grains and sugar. Also it has a lower intake of fruit, vegetables, beans and dark leafy vegetables.

You recently received a grant for “Integrative Transdisciplinary Study of Early-Onset Colorectal Cancer.” What is the goal of this study?

The big goal is trying to understand the characteristics of early-onset colorectal cancer and its risk factors and how they increase cancer risk. We will analyze global trends and data in the U.S. I’m also a molecular pathologist and study immunology and microbiology. So we will analyze tissue, especially microbiota and immune cell traits, to try to link with risk factors.

What might be the impact of that research for patients?

Better understanding of pathogenic markers can give some clues to what kind of approach works to prevent and treat cancer. For example, we have been studying the tissue microbe called Fusobacterium nucleatum, which may be associated with early-onset cancer. Some early-onset colorectal cancer has this bacterium, too. It has been shown to be immunosuppressive, meaning it may suppress the immune response against cancer, causing the cancer to be more aggressive and resistant to immunotherapy. Eliminating these bacteria, possibly with antibiotics that can target it, may improve the treatment outcome.

What is molecular pathologic epidemiology?

Before I started this approach, pathologists and epidemiologists collaborated in a few instances to do studies, but they weren’t really integrated and there wasn’t a clear idea that these two different scientific approaches could be unified.

The molecular pathological approach is to personalize disease diagnostics so that we can treat or prevent it in an individualized way. On the other hand, epidemiology is big data studies with a large number of people over a long time, which is a completely different approach. So, one is individualized, and the other one is big data, big population analysis. I’ve shown that these both can be successfully combined into one field: molecular pathological epidemiology (MPE).

How do you think this area of research will evolve?

MPE will advance with more sophisticated technologies to analyze various cells in cancer. On the other hand, there are challenges to advance early-onset cancer research. I’d like to emphasize we have to work more collaboratively, breaking silos. In order to study early-onset cancer, we have to engage in risk factor assessment from an early age, which normally adult cancer researchers don’t do. We need to work with specialists such as pediatricians and gynecologists who collect this data from prenatal, neonatal, and infant periods. We need to work together to make more life-course cohort studies. And we need to educate more parents and kids about improving their lifestyle so we can prevent disease through this teaching relationship.