Opinion: For Those With Lynch Syndrome, Exercise May Be A Useful Defense Against Colorectal Cancer

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Colorectal cancer (CRC) currently ranks as the fourth most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States.¹ While most CRCs cases arise sporadically, between 5 and 10% of cases are attributed to hereditary cancer syndromes.² Lynch syndrome, characterized by a germline mutation in one of several DNA mismatch repair genes—such as MLH1, MSH2, MSH6, PSM2—or in the EPCAM gene, is the most common hereditary cause of CRC.3 Furthermore, it is associated with an increased risk of several other malignancies, including endometrial and gastric cancer.³

When patients receive a diagnosis of Lynch syndrome, it is natural for them to have questions about the cancer preventive measures they should take. The National Comprehensive Cancer Network (NCCN) recommends initiating colonoscopy screenings at ages 20-25 or 2-5 years before the earliest CRC diagnosis in the family, whichever comes first, and repeating colonoscopy every 1-2 years.⁴ Additional recommendations exist for screening other types of cancer. However, colonoscopy alone may not suffice to prevent CRC. Consequently, patients may inquire about other proactive steps they can take in cancer prevention.

CYCLE-P Study

According to the findings of the prospective, non-randomized, single-site controlled CYCLE-P study (NCT03495674), as published in Clinical Cancer Research, patients with Lynch syndrome who engaged in a 12-month aerobic exercise cycling intervention experienced notable changes.⁵ These changes included a primary exercise outcome—increased oxygen consumption (VO2peak)—and a reduction in inflammatory markers (prostaglandin E) in both the colon and blood, when compared to patients receiving standard care. Additionally, individuals in the exercise group exhibited an elevation in CD8+ T cells and natural killer (NK) cells in the colonic mucosa.

Eligible participants were adults aged between 18 and 50 with Lynch syndrome who had no evidence of active cancer or hadn't undergone any cancer-directed treatment in the preceding 6 months. They were required to be willing to undergo annual screening colonoscopies and have the anatomical capacity for collecting normal mucosa biopsies from the distal colon. Participants with a history of cardiovascular disease or uncontrolled medical conditions were excluded.

In the study, patients in the exercise group (n = 11) engaged in cycling classes lasting 45 minutes per day, three times a week, for 12 months. Most participants utilized a gym, with one participant using a Peloton bike. Regular contact was maintained with participants every 2 weeks to monitor and encourage compliance. Data, such as exercise minutes, sleep duration, and heart rate, were collected using Fitbit devices.

The standard care group (n = 10) did not participate in cycling classes but received counseling from an exercise physiologist regarding current exercise guideline recommendations. The exercise activities of the standard care group were also monitored using Fitbit devices. Both groups of participants completed a total of four study visits, including colonoscopies, blood sample collection, and cardiopulmonary exercise testing (CPET) which assesses their exercise capacity.⁶ Participants in the cycling intervention received $50 at the end of each month to offset the cost of cycling classes. Both groups received $100 after the first CPET and $300 after the second CPET.

The median ages of participants differed between the exercise group (46 years, IQR 40-48) and the standard care group (35.5 years, IQR 34-38), but other baseline characteristics and CPET results were similar between the two groups. The exercise group had a mean adherence rate to the exercise intervention of 51.3%, with a range spanning from 11.5% to 73.1%. The median total weekly exercise minutes for the exercise group were 164 minutes (IQR 88-265) and 14 minutes (IQR 1-57) for the usual care group.

Participants in the exercise group had a 21.6% increase in their mean relative VO2peak (P = 0.0056), while the usual care group had a 2.0% decrease in VO2peak (P = 0.44). This represented a significant difference when the exercise group was compared to the standard group (P = 0.008). The exercise group also had significantly decreased prostaglandin E levels in colonic tissue after the exercise intervention compared to the usual care group (P < 0.05). There was also a decrease in prostaglandin E levels in the blood in the exercise group. The exercise group also had significantly increased numbers of activated NK cells (P = 0.036) and increased CD8+ T cells compared to the standard group.

Nursing Considerations

When patients come across news about an intervention that has been shown to aid in cancer prevention, they may seek guidance from their nursing team members to better understand the implications of the study's findings.

Nurses can inform their patients that this research showcased an improvement in the cardiovascular fitness of patients with Lynch syndrome following a one-year cycling intervention, as evidenced by elevated VO2peak levels. Furthermore, there was a significant reduction in pro-inflammatory markers and an increase in cells that promote the activation of the immune system. These findings collectively suggest that exercise may play a role in cancer prevention by stimulating adaptive antitumor immunity.

The findings of this study emphasize the need to educate and support patients with Lynch syndrome in adopting and maintaining a regular exercise regimen. Beyond the physical benefits, exercise can provide patients with a sense of control and empowerment over their health, fostering a proactive mindset in the face of a challenging diagnosis. It is my hope that this study inspires healthcare providers and patients to embrace the positive impact of exercise in their health journey.

References

1. Cancer stat facts: common cancer sites. National Cancer Institute. Accessed October 10, 2023. https://seer.cancer.gov/statfacts/html/common.html
2. Weiss JM, Gupta S, Burke CA, et al. NCCN guidelines® insights: genetic/familial high-risk assessment: colorectal. Version 1.2021. J Natl Compr Canc Netw. 2021;19(10):1122-1132. doi:10.1164/jnccn.2021.0048
3. Lynch Syndrome. Centers for Disease Control and Prevention. May 3, 2023. Accessed October 10, 2023. https://www.cdc.gov/genomics/disease/colorectal_cancer/lynch.htm
4. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal. Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf Accessed October 10, 2023.
5. Deng N, Reyes-Uribe L, Fahrmann JF, et al. Exercise training reduces the inflammatory response and Promotes Intestinal Mucosa-associated Immunity in Lynch Syndrome [published online ahead of print, 2023 Sep 19]. Clin Cancer Res. 2023;10.1158/1078-0432.CCR-23-0088. doi:10.1158/1078-0432.CCR-23-0088
6. Cardiopulmonary exercise testing (CPET) - American Thoracic Society. Accessed October 10, 2023. https://www.thoracic.org/patients/patient-resources/resources/cpet.pdf.