Background & Aims: Inflammatory bowel disease (IBD) and Lynch syndrome (LS) are both risk factors for colorectal cancer (CRC), however it is unclear if those with LS+IBD have compounded cancer risk or if they would benefit from more intensive surveillance. Our primary aims were to compare the prevalence of CRC in those with LS+IBD vs LS alone, and evaluate factors associated with CRC. Secondary outcomes included describing prevalence and risk factors for colorectal polyps, gastric, small bowel, and gynecologic cancer.

Methods: We performed a retrospective cohort study from the national Epic Cosmos Expertly Determined De-Identified data set (EDDI), which includes >210 million patients from 205 academic and community centers in the United States. EDDI provides anonymized patient- and encounter-level data based on pre-specified discrete data fields, medication orders, diagnostic codes, and billing codes. We included those with a billing, encounter, or problem-list diagnoses of LS from 1/1/2020 to 7/1/2023. We collected sociodemographics, comorbidities, medications, family history and history of neoplasia. Cohort characteristics and neoplasia outcomes were compared using Chi-square tests. Multivariable regression analysis was performed to evaluate factors associated with neoplasia.

Results: Of 24,584 patients with LS, 71.5% were female and 86.4% were white. Genotypes included MLH1 (4.9%), MSH2/EPCAM (6.8%), MSH6 (10.9%), PMS2 (10.4%) and unspecified (66.9%). 568 (2.3%) LS patients had comorbid IBD. Compared to LS patients without IBD, LS patients with IBD were less likely to be Hispanic/LatinX (3.9% vs 5.8%, p<0.0001), more likely to have a personal history of primary sclerosing cholangitis (0.5 % vs 0.02%, p<0.0001), and be prescribed aspirin (6.5% vs 4.4%, p=0.0235). LS+IBD patients had a higher prevalence of CRC (7.7% vs 4.9%, p =0.003), colorectal polyps (39.8% vs 30.8%, p<0.0001), and small bowel cancer (3.5% vs 1.2%, p<0.0001), but there was no significant difference in gynecologic or gastric cancer (Table 1). After multivariable adjustment, IBD (OR 1.55, 1.10-2.18), MLH1 genotype (OR 1.54, 1.21-1.97), increasing age (for age 65-74, OR 4.15, 2.40-7.17), Hispanic ethnicity (OR 1.38, 1.09-1.75) and active/former smoking status (OR 1.33, 1.15-1.54) were independently associated with CRC (Table 2). IBD, genotype, increasing age and were also associated with colorectal polyps and small bowel cancer, with increased BMI and aspirin use also being associated with colorectal polyps.

Conclusions: There is a significantly higher prevalence of CRC, small bowel cancer, and colorectal polyps among those with LS+IBD vs LS alone. IBD, MLH1/MSH2/EPCAM genotype, and increasing age are independent risk factors for neoplasia, suggesting that LS patients with these risk factors may benefit from more intensive surveillance.

Nicole Doria

Appearances