What’s Driving the Rising Rates of Colorectal Cancer in Young Adults?

A Conversation With Christopher Lieu, MD



Guest Editor


Adolescent and Young Adult Oncology explores the unique physical, psychosocial, social, emotional, sexual, and financial challenges adolescents and young adults with cancer face. The column is guest edited by Brandon Hayes-Lattin, MD, FACP, Associate Professor of Medicine and Medical Director of the Adolescent and Young Adult Oncology Program at the Knight Cancer Institute at Oregon Health and Science University in Portland, Oregon.

The study statistics are alarming—and perplexing. According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) colorectal cancer registry, colon cancer incidence among young adults aged 20 to 34 is expected to increase 90% by 2030, and the incidence of rectosigmoid and rectal cancers is expected to rise 124.2% in the same time period.1 While the overall incidence of colorectal cancer in adolescents and young adults remains low—between 1975 and 2000, colorectal cancer accounted for 2.1% of all cancers diagnosed in adolescents and young adults aged 15 to 292—the disease has been increasing in this age group over the past 2 to 3 decades, just as the rate for older adults has decreased.

What is even more troubling, once the cancer is found in young adults, it is often at an advanced stage and less likely to be cured. Although no definitive explanations have been found so far to explain the rising incidence of colorectal cancer among young adults, studies are revealing some intriguing possibilities.

A study presented at the 2016 ASCO Annual Meeting found that while both younger and older patients with colorectal cancer share many genetic changes, younger patients are more likely to have alterations in the CTNNB1 and FAM123 genes, which are associated with the Wnt signaling pathway, an activating mechanism in colorectal cancer.3


Understanding that the incidence is increasing is important not only from a physician’s standpoint always to consider colorectal cancer in a differential diagnosis, even if the patient is really young, but also for the public to understand that there are factors to be aware of, including family history.
— Christopher Lieu, MD

“Our finding is significant because Wnt is one of the most altered pathways in colorectal cancer, and there are drugs currently in development that target the Wnt pathway,” said Christopher Lieu, MD, Director of Colorectal Medical Oncology and Deputy Director of the Cancer Clinical Trials Office at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora, Colorado, and lead author of the study. “It is too early to know for sure, but now that we have identified these differences in the alteration rate in the CTNNB1 and FAM123 genes, we have a rationale to further investigate targeting this pathway in younger patients with colorectal cancer.”

The ASCO Post talked with Dr. Lieu about the reasons colorectal cancer is trending younger, what studies are showing about molecular differences in the tumors of younger and older patients, and the importance of raising awareness of colorectal cancer in younger adults and in the medical profession.

Looking for Explanations

Why is colorectal cancer on the rise in young adults between the ages of 20 and 49?

We do not know the answer. We think it could be caused by a combination of hereditary risk factors, diet and lifestyle, and environmental exposures. The numbers suggest that the majority of these younger patients do not have a hereditary predisposition to develop the cancer, and that is why we think something else has to be going on, but we don’t know what it could be. Is it dietary intake, is it environmental exposure, or is there something different about the way these tumors develop in younger people compared to older people?

We are trying to find the answers.

Age and Outcome

Do younger patients have more favorable outcomes than older patients?

Surprisingly, a study we did looking at whether age is prognostic for overall survival or progression-free survival in patients with metastatic colorectal cancer found that both younger and older age are associated with poorer overall survival and progression-free survival.4 We looked at age as a continuous variable instead of randomly generated age cohorts.

Brandon Hayes-Lattin, MD, FACP

Brandon Hayes-Lattin, MD, FACP

Other studies have shown no difference in overall survival between younger and older patients. The simple fact is that even if younger patients do just as well as older patients, something doesn’t fit because you would expect a younger person who is completely healthy should fare better than a 70-year-old with diabetes and congestive heart failure.

This is just anecdotal, but in my practice, younger patients who developed colorectal cancer were not unhealthy. Many were running triathlons and marathons and led a healthy lifestyle. This is why it is important to do additional studies in this younger age group. We need to learn why these tumors are different.

Raising Awareness

Because the disease is usually discovered at such an advanced stage in younger adults, should screening for colorectal cancer begin before age 50 in the general population?

No, I don’t think so. We want to make sure that screening is cost-effective and that the risk of any cancer screening test does not outweigh the benefits. There are risks associated with colorectal cancer screening tests, including false-negative or false-positive results and complications with invasive procedures. Since the incidence of colorectal cancer is still uncommon in younger adults, we don’t want to expose them to unnecessary costs and complications.

Having said that, understanding that the incidence is increasing is important not only from a physician’s standpoint always to consider colorectal cancer in a differential diagnosis, even if the patient is really young, but also for the public to understand that there are factors to be aware of, including family history. People have to see their doctor if they are having symptoms of the cancer, especially rectal bleeding or blood in the stool.

We also have to do a better job of raising awareness among primary care physicians that younger people can develop colorectal cancer and not to dismiss these symptoms as hemorrhoids or a gastrointestinal disorder without doing a complete physical workup and further testing if warranted.

Risk Stratification

Other than a genetic predisposition, is it possible to identify which young adults are at high risk for developing colorectal cancer?

We are investigating how we might be better able to identify high-risk subgroups in this younger population, but it is too early in the process to know for sure. ■

Disclosure: Dr. Lieu has had a consulting or advisory role with Merrimack.

References

1. Bailey CE, Hu CY, You YN, et al: Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 150:17-22, 2015.

2. Bleyer A, O’Leary M, Barr R, Ries LAG (eds): Cancer Epidemiology in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. National Cancer Institute, NIH pub no 06-5767. Bethesda, Maryland, 2006.

3. Lieu CH, Golemis E, Kim J, et al: Emerging genomic landscape and therapeutic target in young patients with colorectal cancer. 2016 ASCO Annual Meeting. Abstract 3589. Presented June 4, 2016.

4. Lieu CH, Renfro LA, de Gramont A, et al: Association of age with survival in patients with metastatic colorectal cancer. J Clin Oncol 32:2975-2982, 2014.



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