Objectives DNA Microsatellite instability (MSI) due to hypermethylation of the MLH1 gene leading to deficient DNA mismatch repair (MMR) is a frequent finding in sporadic endometrial (EC) and colorectal cancers (CRC). Individuals with germline MMR mutations have an 80% lifetime risk of colorectal cancer (CRC) and follow strict cancer screening protocols. It is unclear if women found to have sporadic MSI high EC have an increased risk of colorectal malignancy. The objective of this study was to determine if there is an increased risk of CRC in patients with MLH-1 promoter hypermethylated EC as compared to patients with microsatellite stable (MSS) disease.
Methods We performed a retrospective cohort study of all cases of EC with known MMR status treated at Massachusetts General Hospital between 2013–2019. Patients with germline MMR mutations were excluded. ICD-9/10 codes from electronic medical records were used to determine the incidence of CRC in the two groups. Chi-squared testing was used to assess for differences in the proportion of CRC between MMR groups with p < 0.05 considered significant.
Results Among 988 patients with EC not associated with a germline MMR mutation, 16% (n=162) had MLH-1 promotor hypermethylation and 84% (n=826) did not. Among those with MLH-1 promotor hypermethylation there were 6 cases (3.6%) of CRC vs. 34 cases (4.1%) in those with MSS disease (p=.743).
Conclusions We found no difference in incidence of CRC in individuals with MLH-1 promotor hypermethylated EC as compared with those with MSS disease. Patients with MLH-1 promotor hypermethylated EC should follow general CRC screening guidelines.
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