Spotlight on colorectal cancer prevention

Recent studies and a clinical practice update focused on colorectal cancer (CRC) prevention with medications or diet.

The American Gastroenterological Association provided practical advice in a clinical practice update and expert review describing the role of medications for the chemoprevention of colorectal neoplasia, which was published online on Feb. 9 by Clinical Gastroenterology and Hepatology. The scope of the review excluded dietary factors and high-risk individuals with hereditary syndromes or inflammatory bowel disease. The resulting best practice advice statements were based on a review of the literature, although a formal systematic review and rating of the quality of evidence or strength of recommendation were not performed. The authors used “should” and “may” to denote statements based on more and less robust evidence, respectively.

The best practice advice statements are as follows:

1. 1. Clinicians should use low-dose aspirin to reduce CRC incidence and mortality in individuals at average risk for CRC who are younger than age 70 years with a life expectancy of at least 10 years, who have a 10-year cardiovascular disease risk of at least 10%, and who are not at high risk for bleeding.
2. 2. Clinicians should consider using aspirin to prevent recurrent colorectal neoplasia in individuals with a history of CRC.
3. 3. In individuals at average risk for CRC, clinicians should not use nonaspirin NSAIDs to prevent colorectal neoplasia due to a substantial risk of cardiovascular and gastrointestinal adverse events.
4. 4. In individuals with type 2 diabetes, clinicians may consider using metformin to prevent colorectal neoplasia.
5. 5. In individuals with CRC and type 2 diabetes, clinicians may consider using metformin to reduce mortality.
6. 6. Clinicians should not use calcium or vitamin D (alone or together) to prevent colorectal neoplasia.
7. 7. Clinicians should not use folic acid to prevent colorectal neoplasia.
8. 8. In individuals at average risk for CRC, clinicians should not use statins to prevent colorectal neoplasia.
9. 9. In individuals with a history of CRC, clinicians should not use statins to reduce mortality.

Next, a prospective study found that the benefits of aspirin on CRC prevention may become most significant after at least six to 10 years of use. Researchers used data from the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) to assess the effects of cumulative average dose and total duration of aspirin use, both in more than 10 years prior to follow-up (remote period) and in the immediate 10 years prior to follow-up (recent period), on CRC risk. Duration and dose of aspirin use were first assessed by the NHS in 1980, with biennial updates thereafter except for in 1986. HPFS participants were first asked about duration and dose of aspirin use in 1986 and 1992, respectively, with regular updates every two years. Results were published online on Feb. 2 by the Journal of the National Cancer Institute.

A total of 123,816 eligible participants were included in duration analyses, with 2,147 incident CRC cases documented. Dose analyses included 113,582 eligible participants, with 1,764 CRC cases documented. Aspirin use more than 10 years before follow-up started (hazard ratio [HR], 0.88 [95% CI, 0.83 to 0.94] per five-year increment) and in the immediate 10 years before follow-up started (HR, 0.90 [95% CI, 0.84 to 0.96] per five-year increment) were similarly important in CRC prevention; however, a five-year lag was required for a clear benefit in the recent period. While the association was not dose-dependent in the remote period, there was dose dependency in the recent period. Compared to fewer than 0.5 standard (325 mg)-dose tablets per week, HRs were 0.91 (95% CI, 0.79 to 1.06), 0.87 (95% CI, 0.77 to 0.98), and 0.76 (95% CI, 0.64 to 0.91) for doses of 0.5 to fewer than 1.5, 1.5 to fewer than 5, and 5 or more tablets per week, respectively. Limitations of the study include its observational design and the fact that study participants were all health care professionals and were predominantly White, the authors noted. “Our findings may have provided new initial clues that [are] of practical importance in altering patient management, including the potential benefit of initiating using aspirin at even lower doses (e.g., 23-70 mg/day) among persons with a life expectancy exceeding 15-20 years, and the possibility of using lower dose (70 mg/day) among persons (especially for those ≥70 years of age) that have already used aspirin for at least 10 years,” they concluded.

Dietary factors may also play a role in the development and prevention of CRC, according to an umbrella review and meta-analysis of prospective observational studies. Researchers assessed 45 meta-analyses that described 109 associations between dietary factors and CRC incidence. Overall, 35 (32.1%) of the associations were nominally statistically significant using random-effects meta-analysis models. Seventeen associations demonstrated large heterogeneity between studies, and 11 had small-study effects. The primary analysis identified five (4.6%) convincing, two (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations, according to results published Feb. 16 by JAMA Network Open.

There was convincing evidence of an association of intake of red meat (high vs. low) and heavy alcohol intake (≥4 drinks/d vs. 0 or occasional drinks) with the incidence of CRC. In contrast, convincing evidence was found for three inverse associations with CRC risk: higher versus lower intakes of total dietary fiber, calcium, and yogurt. The evidence for convincing associations remained robust following sensitivity analyses. As for highly suggestive evidence, higher intake of total dairy products (e.g., milk, cheese, yogurt) was associated with significant CRC risk reduction compared with lower intake. On the other hand, a moderate intake of alcohol (defined as more than 1 to 3 drinks per day but not more than 4 per day) was associated with an increase in the incidence of CRC compared with 0 drinks or occasional drinking. Among other limitations, some forms of bias (e.g., recall bias owing to self-reported diet) are possible, the authors noted. “The findings of this study support existing recommendations for diet in the primary prevention of CRC, emphasizing higher intakes of dietary fiber, calcium, and yogurt and lower intakes of red meat and alcohol,” they concluded. “Emerging evidence supports a possible role for overall dietary patterns that, in totality, emphasize habitually consuming fruits, vegetables, grains, and low-fat dairy and reducing red meat and alcohol intake.”