Colorectal Cancer: Disease Risk and Prevention

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Worldwide, colorectal cancer (CRC) is the second most common cancer in women and the third most common in men.1 Global statistics estimate that 1.09 million deaths were due to CRC in 2019 and more than 1.9 million new cases of CRC were diagnosed in 2020.1 In the United States, the American Cancer Society ranks colon and rectum cancers third for new cancer cases and second for cancer-related deaths when statistics for men and women are combined.2,3

Family history of CRC, personal history of inflammatory bowel disease, or family history of a hereditary CRC syndrome such as Lynch syndrome are all considered high-risk factors for colon and rectum cancers. As with genetics, advanced age and race are other unmodifiable risk factors for CRC. While early-onset CRC in patients younger than 50 years of age accounts for approximately 10% of current diagnoses and the incidence is increasing in this population,4 the majority of CRC cases are diagnosed in adults over the age of 50. For Black adults in the US, CRC is the third most common cancer. The rate of new colon and rectum cancer cases is highest among this population, with incidence rates 21% and 18% higher in Black men and women respectively compared to white adults.5,6

While some risk factors cannot be changed, others may be modified to help decrease the chances of developing colon and rectum cancers. What lifestyle-based considerations, behaviors, and therapeutic approaches may help lower the risk of disease?

Lifestyle Factors, Exposures, and Comorbidities

Several lifestyle-based risk factors have been associated with an increased risk of developing CRC, including smoking, decreased levels of physical activity, increased sedentary behaviors, increased alcohol intake, decreased consumption of fiber and plants, and increased consumption of red and processed meats.7 A 2022 umbrella review and meta-analysis (N=14 meta-analyses) evaluated the current data on sedentary behavior (including total sitting, occupational sitting, recreational sitting, and TV-viewing time) in relation to cancer incidence.8 Specific to colon and rectum cancers, the results found that sedentary behaviors significantly increased the development risks by 25% and 7%, respectively.8 A 2022 prospective diet-wide association study evaluated 92 food and nutrient intakes in relation to CRC development (N=386,792 participants) and echoed previous findings for a significant positive association between alcohol intake and CRC risk (hazard ratio per one standard deviation=1.07; 95% CI: 1.04-1.09).9

Excess weight and obesity,7 gut dysbiosis characterized by a loss of protective bacteria, an enrichment of pathogenic and cancer-promoting bacteria, and possible altered fungal composition,10,11 as well as comorbidities that include type 2 diabetes,12 inflammatory bowel disease,12,13 and periodontal disease,14 are all reported as potential risk factors for CRC. Environmental toxicant exposures, including proximity to industrial complexes, may also increase the risk of CRC development.15,16 A 2020 multi case-control study included 557 CRC cases and 2,948 controls in 11 provinces in Spain.15 Distances between the subjects and the 134 industrial complexes in the study area were computed. Results showed a significantly increased odds of CRC near industries for all distances analyzed, from 1 km (OR=2.03, 95% CI: 1.44-2.87) to 3 km (OR=1.26, 95% CI: 1.00-1.59).15 Greater odds of CRC were reported for industries releasing air pollutants versus pollutants via water routes.15

Early-onset and late-onset colorectal cancer

As mentioned, the majority of CRC cases are diagnosed in patients who are over the age of 50, yet incidence of early-onset CRC is increasing in the US and other industrialized countries, and patients often present with advanced disease, which has led to an increase in CRC-related deaths in younger patients.4,17 In response to the increasing cases of early-onset CRC, in May 2021, the US Preventive Services Task Force lowered the recommended age for CRC screening for those adults at average risk from 50 to 45.18 However, due to the recency, the effectiveness of earlier screening on outcomes for early-onset CRC has not yet been evaluated.

Research studies continue to investigate the etiology of early-onset CRC to help identify risk factors and clarify characteristics that may distinguish the disease process and outcomes from colon and rectum cancers in older adults.13,19 A 2022 systematic review and meta-analysis of 20 studies identified several significant risk factors for early-onset CRC, including CRC history in a first-degree relative (RR=4.21, 95% CI: 2.61-6.79), hyperlipidemia (RR=1.62, 95% CI: 1.22-2.13), obesity (RR=1.54, 95% CI: 1.01-2.35), and alcohol consumption (high vs. non-drinkers) (RR=1.71, 95% CI: 1.62-1.80).20 A cohort study (N=769,871 individuals with CRC; 82.7% identified as white) compared the demographics and rates of survival for patients diagnosed with early-onset CRC with those diagnosed with CRC between the ages of 51 and 55.17 Those patients with early-onset CRC were more likely to be diagnosed at an advanced stage, to have rectal tumors, to have less comorbidities, to be female, to have Medicaid, and to identify in the “other” race category.17 Please note that the published demographic analysis in this study was limited to racial identifiers of white, Black, and other.

Lifestyle Modifications for Prevention

In addition to preventative CRC screenings, the Centers for Disease Control and Prevention points to a nutrient-dense diet high in fruit, vegetables, and whole grains and low in animal fats for potentially reducing risk of colon and rectum cancers.21 Other lifestyle-based approaches that may help lower CRC risk include increasing physical activity, maintaining a healthy weight, limiting alcohol consumption, increasing soluble and insoluble fiber consumption, and avoiding smoking.21,22 

A large 2022 meta-analysis of cohort and case-control studies (N=3,059,009 participants) investigated the relationship between various plant-based diets (i.e., vegan and vegetarian diets, Mediterranean diet, prudent diet, semi-vegetarian diet, and DASH diet) and risk of digestive system cancers.23 Overwhelmingly, the reported results suggested that plant-based diets were significantly associated with both reduced risk of developing and odds of having neoplasms in the digestive system (cohort adjusted RR=0.82, 95% CI: 0.78-0.86; case-control adjusted OR=0.70, 95% CI: 0.64-0.77).23 Specific to colon and rectum cancers in cohort studies, a plant-based diet significantly reduced the risk of colorectal, rectal, and colon cancers by 24%, 16%, and 12%, respectively.23

Additional studies have evaluated the impact of specific nutrients on CRC risk and have associated lower colon and rectum cancer risks with higher intakes of calcium, phosphorous, magnesium, potassium, riboflavin, beta-carotene, and vitamin D.9,24,25 Further studies are needed to clarify what mechanisms may be involved, what nutrient amounts may have the most protective influence, and how micronutrient deficiencies or inadequacies may impact CRC risk. Most recently, a 2022 meta-analysis of primarily observational studies investigated the association between circulating 25-hydroxyvitamin D levels and risk of incidence of CRC precursors (i.e., adenomatous polyp, serrated adenoma/polyp).26 Analysis indicated that higher circulating 25(OH)D levels were associated with a 21% decreased risk of CRC precursor development (RR=0.79, 95% CI: 0.67-0.92).26

Research continues to elucidate the various risk factors involved in the development of both early-onset and late-onset CRC. Foundational functional medicine interventions for gut balance and health such as nutrition and movement are among those modifiable lifestyle factors that may help in cancer prevention and are also low-risk therapeutic approaches to optimize a patient’s overall health and wellness.

Learn More About Functional Medicine

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