Regular and intense aerobic exercise may be effective at reducing the risk of colorectal cancer in patients with Lynch syndrome by improving the immune system's ability to detect and remove potentially harmful cells, according to a novel study published by Deng et al in Clinical Cancer Research.
Background
Lynch syndrome, a hereditary condition that affects over 1 million U.S. individuals, carries a high lifetime risk of colorectal cancer and endometrial cancer. Male patients with the condition have a 60% to 80% risk of developing colorectal cancer, whereas female patients with the condition have a 40% to 60% risk of developing colorectal cancer. Female patients also face the same amount of risk of developing endometrial cancer.
Study Methods and Results
In the new nonrandomized study, the researchers assigned 21 patients aged 18 to 50 years with Lynch syndrome to partake in a high-intensity training regimen involving three 45-minute cycling sessions per week (n = 11) or receive standard care (n = 10). All of the patients who participated in the standard care group were told about the benefits of exercise but were not assigned a training regimen.
Patients in the training group recorded a median of 164 weekly exercise minutes at a heart rate of > 70%, whereas the standard care group recorded a median of 14 weekly exercise minutes.
At the start of the study, both groups completed a baseline health questionnaire and underwent a standard-of-care lower gastrointestinal endoscopy with biopsies and blood collection. Cardiopulmonary exercise testing was performed at the second visit, within 30 days of the primary endoscopy. Further, all of the patients received a 1-year endoscopy followed by cardiopulmonary exercise testing at the fourth checkup, within 30 days of the 1-year endoscopy.
After a follow-up of 12 months, the researchers discovered that the patients with Lynch Syndrome who participated in the high-intensity training regimen saw reduced levels of prostaglandin E2 in both the colon and the blood and increased levels of natural killer cells and CD8-positive T cells—suggesting an increased immune response in the colon.
Expression analyses by next-generation sequencing demonstrated statistically significant changes in gene expression in the normal colorectal mucosa between the training group and standard care group. In the patients who participated in the training regimen, 13 genes became more active, whereas 33 genes became less active when compared with those who received standard care. The researchers found that the activated genes were involved in immune signaling pathways, and the suppressed genes were linked to muscle contraction and metabolism.
The researchers reported that the patients involved in the study did not experience any significant adverse events.
Conclusions
“It was mind-blowing to me that exercise induced such strong and durable change,” highlighted senior study author Eduardo Vilar-Sanchez, MD, PhD, Professor of Clinical Cancer Prevention at The University of Texas MD Anderson Cancer Center. “We found that high-intensity training not only enhances how the body could fight cancer at its earliest stages, but it also gives many other health benefits,” he added.
The researchers noted that future randomized clinical trials may be needed to confirm the preventive efficacy of aerobic exercise training in patients with Lynch Syndrome and to further elucidate the possible immune-related pathways underlying any reductions in cancer risk.
“It can be difficult for patients to commit to taking a pill,” Dr. Vilar-Sanchez stressed. “If we are able to validate the preventive benefits of this approach in future studies, we hope to offer a ‘lifestyle prescription’ and give patients [with Lynch syndrome] a new way to possibly lower their cancer risk over time,” he concluded.
Disclosure: The research in this study was supported by the Duncan Family Institute for Cancer Prevention and Risk Assessment, the T. Boone Pickens Fund, the National Cancer Institute, and the Moon Shots Program at The University of Texas MD Anderson Cancer Center. For full disclosures of the study authors, visit aacrjournals.org.
