Research establishes strong association between family history and increased risk of colorectal cancer in patients with inflammatory bowel diseases

Aug. 16, 2019

Past studies have identified several risk factors that are associated with the development of colorectal cancer (CRC) in patients with inflammatory bowel diseases (IBDs), including disease duration, disease extent, disease severity (including histological disease activity), the presence of primary sclerosing cholangitis (PSC) and family history of CRC.

How much impact does a family history of colon cancer have on the development of CRC in patients with IBD? To address this question, Mayo Clinic researchers conducted a population-based study that estimated the risk of CRC in a cohort of patients with IBD and the significance of family history of CRC in a first-degree relative. The results of this study were published in Clinical Gastroenterology and Hepatology in 2019.

Methods

Mayo Clinic researchers identified 9,505 Utah residents with IBD using patient data from Intermountain Healthcare and University of Utah Health databases collected from Jan. 1, 1996, through Dec. 31, 2011. The team also identified individuals with a family history of CRC in a first-degree relative (parent, child or full sibling) using the Utah Cancer Registry and linked them to genealogical pedigrees from the Utah Population Database. The researchers then calculated CRC incidence in the population diagnosed with IBD and in age- and sex-matched individuals from the general population database using standardized incidence ratios (SIRs). Only CRC diagnoses occurring after the diagnosis of IBD were included in this analysis.

Among the 9,505 individuals with IBD included in this study, 4,421 (46.5%) were diagnosed with ulcerative colitis, 5,084 (53.5%) were diagnosed with Crohn's disease, and 468 (4.9%) had a concurrent diagnosis of PSC.

Results

According to Niloy Jewel (Jewel) Samadder, M.D., a specialist in gastroenterology and hepatology at Mayo Clinic's campus in Arizona and the study's lead investigator, the team's data analysis yielded several interesting findings:

  • When compared with individuals from the general population, individuals with all forms of IBD studied (Crohn's disease, ulcerative colitis, with or without concurrent PSC) had a significantly increased risk of CRC, with an SIR of 4.3; 95% confidence interval (CI), 3.5 to 5.1.
  • Individuals with ulcerative colitis had an SIR of 5.2; 95% CI, 3.9 to 6.6.
  • Individuals with Crohn's disease had an SIR of 3.4; 95% CI, 2.3 to 4.4.
  • Individuals with IBD and a concurrent diagnosis of PSC had the greatest risk of CRC, with an SIR of 14.8; 95% CI, 8.3 to 21.2.
  • When compared with individuals from the general population, individuals with IBD and a history of CRC in a first-degree relative had a nearly eightfold increase in risk of CRC, with an SIR of 7.9; 95% CI, 1.6 to 14.3 and an intracohort relative risk of 1.88; 95% CI, 0.8 to 4.3. This supports the notion that having a family history of CRC increases the already elevated risk of CRC in patients with IBD by nearly twofold.

Dr. Samadder notes that the study results also suggest that the risk of CRC is greater in the proximal colon when compared with distal or rectal cancers and that males with IBD are at greater risk of developing CRC than are females with IBD.

Conclusions

According to Dr. Samadder, these findings have multiple direct implications for clinicians. "Understanding that individuals with IBD have an elevated risk of colorectal cancer and that having a first-degree relative with colorectal cancer significantly increases that risk should impact the way we care for patients with IBD," explains Dr. Samadder. "Our results underscore the importance of obtaining a family history in these patients. And knowing that a confirmed family history is associated with an almost eightfold increase in cancer risk means that we should enroll these patients in aggressive surveillance programs."

Francis (Frank) A. Farraye, M.D., M.Sc., a gastroenterologist in the Inflammatory Bowel Disease Clinic at Mayo Clinic's campus in Jacksonville, Florida, concurs. "Although the incidence of colorectal cancer in patients with IBD appears to be decreasing, this study shows us that certain subgroups of patients remain at increased risk and need more-frequent surveillance colonoscopy exams," says Dr. Farraye. "For this reason, it is important for gastroenterologists to include a family history of colon cancer in a first-degree relative as a significant risk factor for the development of cancer and to use this information when determining intervals between colonoscopic procedures."

Talha A. Malik M.D., M.P.H., a gastroenterologist in the Inflammatory Bowel Disease Clinic at Mayo Clinic's campus in Arizona adds: "While it is known that the higher risk of CRC in patients with IBD when compared with the general population is further increased in those with a family history of colon cancer, this study provides us with an objective measure of that risk. The findings of this study suggest that after a concurrent diagnosis of PSC, a family history of CRC in a first-degree relative of a patient with IBD may be the next major risk factor."

For more information

Samadder NJ, et al. Family history associates with increased risk of colorectal cancer in patients with inflammatory bowel diseases. Clinical Gastroenterology and Hepatology. 2019;17:1807.