Are inflammatory bowel disease patients more at risk of colorectal cancer?

In a recent study published in the journal Frontiers in Medicine, researchers analyzed data from a large cohort of inflammatory bowel disease (IBD) patients and compared the risk and frequency of colorectal cancer (CRC) among these patients to that of the general population.

Background

Colorectal cancer poses a considerable risk of complications in individuals diagnosed with inflammatory bowel disease. Previous research has indicated that individuals with colitis are at an increased risk of developing colorectal cancer over time.

Many studies have revealed that colitis-associated colorectal cancer rates range from 5% after 10 years of disease to 40% after 25 years. A comprehensive meta-analysis conducted in 2001 found that individuals with ulcerative colitis (UC) had a prevalence rate of 3.7% for developing colitis-associated colorectal cancer.

The pathophysiological mechanisms underlying colitis-associated colorectal cancer differ from those in sporadic colorectal cancer. In the case of colitis-associated colorectal cancer, the disease typically initiates as indefinite or low-grade dysplasia, gradually advancing to high-grade dysplasia and eventually transforming into an adenocarcinoma.

The management and ongoing care of dysplasia or carcinoma in individuals with IBD pose significant challenges. These challenges arise from the necessity of conducting meticulous endoscopic examinations, the requirement for total proctocolectomy in cases of multifocal dysplasia, and the evaluation of dysplasia within colonic strictures.

Screening techniques such as random biopsies, chromoendoscopy, and high-resolution endoscopy are employed to detect any potential precancerous lesions within the colon. By adhering to this proactive approach, individuals can significantly lower their risk of colorectal cancer. The present study assessed the prevalence and risk factors contributing to the development of colorectal cancer in individuals diagnosed with inflammatory bowel disease.

About the study

The study cohort included adult patients (aged ≥ 18 years) who had been diagnosed with inflammatory bowel disease. The patients were identified using data-driven algorithms. Data from 2000 to 2021 were extracted from Clalit, Israel, using the MDClone platform.

Demographic data, including age, sex, age at diagnosis, body mass index, smoking habits, and ethnicity, were carefully recorded. The authors explored different treatment options, including 5-aminosalicylic acid (5-ASA), mercaptopurine, anti-TNF, azathioprine, glucocorticoids, methotrexate, vedolizumab, and ustekinumab.

Additionally, researchers incorporated data on all-cause mortality. The findings were categorized into data related to Crohn’s disease (CD) and ulcerative colitis and analyzed for patients diagnosed with and without colorectal cancer.

Data are reported as mean ± standard deviation for continuous variables, while categorical variables were expressed as percentages (%) of the total. Chi-square tests were used to investigate univariate associations between categorical risk factors and the likelihood of developing cancer. T-tests were used to analyze disparities in continuous risk factors, which followed a normal distribution between the groups.

Logistic regression models were used to investigate the intricate interconnections between various risk factors and the likelihood of developing colorectal cancer. Before incorporating the variables into the model, a thorough evaluation of the multicollinearity of the variables was conducted using the Variance Inflation Factor (VIF) statistic.

The sequencing of variables in the model was established based on the magnitude of the univariate Odds Ratio. Statistical analyses were performed using IBM SPSS version 26 for data analysis and interpretation, and statistical significance was determined using a P-value < 0.05.

Results

The investigation reaffirmed that individuals with ulcerative colitis and Crohn’s disease have a higher incidence of colorectal cancer than the general population. Additionally, individuals with colorectal cancer tend to be older, exhibit a higher incidence of associated health conditions, and experience a heightened mortality risk.

While individuals with ulcerative colitis and diabetes mellitus (DM) were found to be more prone to developing colorectal cancer, this association was not observed in patients with Crohn’s disease. While the findings of increased colorectal cancer incidence in UC patients support those from a Canadian study, other studies reported declining rates of colorectal cancer and mortality in inflammatory bowel disease patients, potentially due to improved screening and advanced treatment.

The colorectal cancer incidence rate in ulcerative colitis patients in the present study was 2.1%, which was lower than that in the Canadian study; however, inflammatory bowel disease patients still show higher colorectal cancer rates compared to the general population, which warrants more focused surveillance.

In terms of all-cause mortality, colorectal cancer considerably increased the death rate of inflammatory bowel disease patients, which was 44-50% compared to 9-12% in inflammatory bowel disease patients without colorectal cancer. Elevated occurrences of metabolic syndrome were identified in inflammatory bowel disease patients with colorectal cancer, potentially serving as a contributing factor to the heightened rates of mortality. The authors also found that individuals with colorectal cancer exhibit a higher prevalence of comorbid conditions compared to prior investigations.

Primary sclerosing cholangitis (PSC) was identified as a significant risk factor for colorectal cancer in patients with inflammatory bowel disease. A significant correlation was also found between the administration of glucocorticoid steroids, the presence of diabetes mellitus, and the development of colorectal cancer.

Glucocorticoids have been found to influence colorectal cancer through their ability to suppress the host immune system and affect the behavior of r cells. Notably, univariate analysis revealed a significant correlation between anti-TNF treatment and decreased risk of colorectal cancer among individuals with inflammatory bowel disease.

Conclusion

In conclusion, the authors identified several factors that could increase the risk of colorectal cancer development in patients with inflammatory bowel disease. Age at diagnosis, primary sclerosing cholangitis, use of glucocorticoids, and diabetes mellitus in patients with ulcerative colitis were the key risk factors for colorectal cancer in ulcerative colitis patients compared to the general population.

However, while primary sclerosing cholangitis, age at diagnosis, and glucocorticoid treatment were the major predictors for colorectal cancer in Crohn’s disease patients, diabetes mellitus was not.  These findings have practical implications for the follow-up and management of inflammatory bowel disease patients, especially those with risk factors for colorectal cancer. Based on the study results, the authors recommend special consideration for inflammatory bowel disease patients in follow-up for colorectal cancer.