Spotlight on CRC risk factors

Recent studies found that patients exposed to antibiotics had greater odds of developing colorectal cancer (CRC) and that obesity at different ages during early adulthood was strongly associated with an increased risk of early-onset CRC.

Recent research focused on risk factors for developing colorectal cancer (CRC) overall and early-onset CRC in particular.

The first study found that patients exposed to antibiotics had a 25% higher chance of developing CRC than those who were not exposed. Researchers conducted a matched case-control study at general practice centers participating in the Integrated Computerised Network database in Flanders, Belgium. They matched 1,705 cases of CRC diagnosed from 2010 through 2015 to 6,749 controls by age, sex, comorbidity, and general practice center. The primary outcome measure was the association between the number of prescriptions for oral antibiotics and the incidence of CRC over a period of one to 10 years. Results were published Dec. 10 by BMJ Open.

Overall, 5,217 antibiotic prescriptions were prescribed for the cases versus 18,263 for the controls, resulting in a total per patient average of 3.06 and 2.71, respectively, during an average of nine years of observation. There was a significantly increased risk of CRC (crude odds ratio, 1.26; 95% CI, 1.10 to 1.45) in patients with one or more antibiotic prescriptions compared with those with none, and this result remained significant after adjustment for the presence of type 2 diabetes (odds ratio, 1.25; 95% CI, 1.10 to 1.44). There was no dose-response relationship detected. The main limitations of the study were the absence of known risk factors for CRC (particularly smoking and obesity) and the potential for incomplete patient data, as Belgian patients are free to visit different clinicians of their choice, the authors noted. “One possible explanation for our results might be the influence of antibiotics on the human gut, which contains a diverse microbial community and has a crucial role in the defence against pathogenic bacteria. … Our results do support rational use, a trend which seems to become stronger due to the increased presence of antibiotic resistance,” they concluded.

The second study found that obesity in early adulthood is strongly associated with an increased risk of early-onset CRC. Researchers looked at the DACHS study, a population-based case-control study from Germany, to assess the association of body mass index (BMI) at different ages during early adulthood with early-onset CRC. Their analysis included a subset of 747 patients with CRC and 621 controls who were younger than age 55 years, the age cutoff they used to define early-onset CRC. Self-reported height and weight at ages 20 and 30 years and at about 10 years before diagnosis or interview were recorded in personal interviews. Results were published Dec. 12 by Gastroenterology.

Compared to participants with a BMI less than 25 kg/m2, those with a BMI of 30 kg/m2 or greater (obesity) at age 20 years, age 30 years, and about 10 years before their diagnosis/interview had adjusted odds ratios of 2.56 (95% CI, 1.20 to 5.44), 2.06 (95% CI, 1.25 to 3.40), and 1.88 (95% CI, 1.30 to 2.73) for developing early-onset CRC, respectively. The association between higher BMI and early-onset CRC risk was particularly pronounced in women and in patients with no history of large bowel endoscopy, although tests for interactions did not reach statistical significance. Among other limitations, the relatively small number of CRC cases and controls younger than age 55 years, particularly those younger than age 50 years, restricted power of the analysis, the authors noted. “Despite its limitations, our study demonstrates that overweight and obesity at early adulthood are strongly associated with increased risk of early-onset CRC,” they concluded. “It thereby strongly supports suggestions that recent increases in prevalence of obesity in younger generations may be an important factor in the increases in incidence of early-onset CRC in many countries.”

The third study, a systematic review, also focused on early-onset CRC, finding that greater alcohol intake and obesity had the strongest association with increased early-onset CRC risk. Researchers looked at 26 studies that evaluated diet, alcohol, physical activity, BMI, and smoking and their role in early-onset CRC. They excluded studies not reporting specific results for populations with CRC who were younger than age 50 years, the age cutoff they used to define early-onset CRC. Results were published Nov. 25 by Cancers.

In addition to alcohol use and obesity, additional risk factors for early-onset CRC included low physical activity, cigarette smoking, sugary drink consumption, processed meat consumption, and a diet poor in fruits and vegetables, the review found. “Several scientific societies have been calling attention to the increasing incidence of [early-onset] CRC for over a decade,” the authors wrote. “It is time for concrete and discrete actions including awareness campaigns. Young adults with alarm symptoms must seek medical advice earlier and general practitioners need to consider CRC in young adults even without a family history of CRC.”

For more on early-onset CRC, read the cover story of the September ACP Internist, which looked at recent trends and explained the rationale behind new guidance that recommends screening younger adults for CRC, including a recent U.S. Preventive Services Task Force recommendation that lowered the age to start screening from 50 years to 45 years.