Association of Germline Variants and Colon Polyp Phenotypes in Patients with Hereditary Diffuse Gastric Cancer.

BACKGROUND AND AIMS

Germline variants resulting in E-cadherin loss of function result in an increased risk of diffuse type gastric cancer and lobular type breast cancer. However, the risk of developing other epithelial neoplasms, specifically colorectal cancer, is unknown.

METHODS

Patients enrolled in a prospective natural history study of hereditary gastric cancer who underwent at least one colonoscopy were evaluated.

RESULTS

Out of 300 patients with pathogenic or likely pathogenic variants, 85 underwent colonoscopy. More than half of patients (56%, 48/85) had at least one colorectal polyp. Most of those patients (83%, 40/48) had at least one precancerous polyp (adenoma or sessile serrated lesion). More than half (56%) of patients younger than age 45 had a colorectal polyp. Of those with polyps, the most frequent variant type was canonical splice site (27%, 13/48) followed by nonsense (21%, 10/48). There was no association between variant type and increased likelihood of colorectal polyps.

CONCLUSIONS

In summary, a majority of variant carriers who underwent colonoscopy had colorectal polyps detected, and most subjects were less than 45 years old. This study of colorectal cancer risk based on the prevalence of colorectal polyps in the population requires further investigation to appropriately counsel patients on colorectal cancer screening. Clinical trial registry website: https://clinicaltrials.gov/. Clinical trial number: NCT03030404.