Early-Age Onset Colorectal Cancer Summit, Day 2 A Call to Action: Keynote address by Dr. Stephen B. Gruber highlights need for greater examination of CRC risk factors

Suggesting a call to action for a more comprehensive and collaborative effort against the rise of colorectal cancer in patients under 40, Stephen B. Gruber, MD, PhD, MPH, presented the Keynote Address of the seventh annual Early-Age Onset Colorectal Cancer Summit on Saturday, May 15.

Gruber’s lecture was the highlight of Day 2 of the three-day conference, which is being held online in a virtual format because of ongoing Covid-19 precautions. It is organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death.

Gruber, the vice president of the City of Hope National Medical Center in Duarte, Calif., began his presentation with the story of a young patient, who at age 28, was diagnosed with colon cancer that led to metastatic disease and ultimately her death despite having had no known risk factors for colon cancer.

Despite all of the best efforts to understand how she developed colon cancer at such a young age, it wasn’t possible to trace her disease back to any specific genetic or environmental causes. Unfortunately, that’s the status quo for early age onset colorectal cancer as of 2021, Dr. Gruber said. Although overall incidence rates of colorectal cancer have declined over the past 30 to 40 years, the incidence rate has increased substantially since the mid-1990s in adolescents and young adults.

According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths in the U.S. in 2021. The overarching etiology of the disease has not been established; there is no definitive cause of colorectal cancer.

From 2013 to 2017, incidence rates dropped by about 1 percent each year. But that downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2 percent in people younger than 50 and 1 percent in people 50 to 64.

“The reasons remain unknown. We don’t know why cancer is increasing in this group,” Dr. Gruber said. “As we think about all of the possible explanations, including Western-style diet, obesity, physical inactivity, antibiotic use, especially in the early life period of time, it’s not clear why this increase incidence and epidemic of early onset colorectal cancer is being observed.”

Dr. Gruber presented regional findings from his experience and research at the City of Hope National Medical Center in Duarte, Calif., work from the USC Norris Comprehensive Cancer Center in Los Angeles, as well as numerous other national and international studies to help understand some of the reasons that might be contributing as to why the disease is increasing in younger people.

He presented papers that outlined risk factors classified into systems and institutions, including screening policies within healthcare systems that contribute to early diagnosis or fail to diagnose. He questioned how microbiome changes within family environments could impact the change in incidence of the disease, and highlighted papers that explored the possibilities of germline genetics.
He referenced two papers based on studies of colorectal cancer patients under the age of 40 and under the age of 35 that showed relatively low relationships to genetic predisposition based on incidence rates of germline mismatch repair mutations (Lynch Sydrome) bi-allelic MutYH mutations or Li-Fraumeni Syndrome.
“These data are actually quite consistent, whether or not from a single institution or whether or not it’s from a large national family registry over a longer period of time, what we’re actually recognizing is that much of what we actually see is not easily explained by mendelian cancer genetic syndromes,” Dr. Gruber said.
He also explored whether or not population genetics is a likely explanation for the rising incidence of early age onset colorectal cancer. Gruber pointed out that polygenic risk scores — which can identify numerous, individual loci across the human genome that contribute modest risk of colorectal cancer — can ultimate help measure genetic susceptibility. But he said doubts that any singular genetic factor has influenced the rise in adolescent and early adult incident rates.
Dr. Gruber put a lot of his emphasis on the need to address modifiable risk factors as possible correlations to the rise of early-age onset colorectal cancer risk. He highlighted a paper that presented factors that decreased risk (including aspirin, physical activity, statins, vegetable consumption) and those that increased risk (alcohol consumption, Body Mass Index, smoking, processed meat consumption).

He also specifically highlighted coffee consumption and the risk of colorectal cancer and highlighted a study conducted by Stephanie Schmit of the Cleveland Clinic that showed the more coffee people drank, the lower their risk of colorectal cancer. He also pointed out that decrease in coffee consumption and the slight rise of energy drinks over the past decade or so might have led to a microbiome change that might have led to increased risked, but he said it would be hard to postulate that any single risk would be hard to correlate that to the rise in early onset colorectal cancer incidence.

Dr. Gruber also acknowledged and expressed concern about the significant factor that systemic racism plays in the inability to address these disparities in incident and survival rates. He pointed out that the survival rates for those who have early onset colorectal cancer are lowest among individuals with lower socioeconomic status, while the highest survival rates are associated with the people with the highest socioeconomic status.

Ultimately, more questions than answers still remain in the fight against the rising tide of early-age onset colorectal cancer.

“I think it’s actually less likely to be polygenetic risk than it is poly risk, which will include things like medications, physical activity, diet and other trends and changes in risk factors that hopefully we will be able to explore with the same specificity that we are now understanding through genetic studies,” Dr. Gruber said. “It is going to take our collaboration and a lot of work to answer the question that we do not yet understand: Why is there an epidemic of early age onset of colorectal cancer? We have an obligation and an opportunity to understand why the risk of colorectal cancer is rising in early age onset individuals.”

Other highlights of Day 2 included Session II: “The Dimensions of the EAO-CRC Problem: Do We Have Accurate, Regular, Up to Date Measurement of Key Metrics Describing the Early Age Onset Colorectal Cancer Public Health Crisis.” That included an updated about the rising early-onset CRC trends and racial disparities, the impact of COVID-19 on CRC screening and an under-19 incidence and mortality report. Session III was a panel discussion that explored “Risk Assessment/Family History Ascertainment” and included discussions about CRC screening guidelines, increased access to genetic testing and patient access to appropriate care.

To watch Friday’s or Saturday’s presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded programs.

The Early-Age Onset Colorectal Cancer Summit continues on Sunday, May 16 with Session IV: a moderated panel discussion titled, “How to Provide Timely, Effective, Quality of Life & Fertility Preserving Treatment: What Are Key Elements of Coordinated Care for Early Onset Colorectal Cancer?” at 10:30 a.m. ET. A panel of experts will offer input about patient perspective, nurse navigation, genetics, medical oncology and new therapeutics, surgery, financial burden/toxicity, radiation oncology, psychological needs, pediatrics and palliative care.

That will be followed at 1 p.m. ET by breakout sessions about “Understanding and Addressing Disparities in Early-Age Onset Colorectal Cancer” and “Integrating Music Therapy in Cancer” before the conference concludes with Session V at 2:25 p.m. ET, a program titled “How Did This Happen? Investigating the Causes of Early Onset Colorectal Cancers.”