Is it all Lynch syndrome? An assessment of family history in individuals with mismatch repair-deficient tumors

Katherine M. Dempsey, Russell Broaddus, Y. Nancy You, Sarah Jane Noblin, Maureen Mork, Bryan Fellman, Diana Urbauer, Molly Daniels, Karen Lu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Purpose: Mismatch repair-deficient (MMRD) colorectal cancer (CRC) and endometrial cancer (EC) may be suggestive of Lynch syndrome (LS). LS can be confirmed only by positive germ-line testing. It is unclear if individuals with MMRD tumors but no identifiable cause (MMRD+/germ-line-) have LS. Because LS is hereditary, individuals with LS are expected to have family histories of LS-related tumors. Our study compared the family histories of MMRD+/germ-line- CRC and/or EC patients with LS CRC and/or EC patients. Methods: A total of 253 individuals with an MMRD CRC or EC from one institution were included for analysis in one of four groups: LS; MMRD+/germ-line-; MMRD tumor with variant of uncertain significance (MMRD+/VUS); and sporadic MSI-H (MMRD tumor with MLH1 promoter hypermethylation or BRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM 1,2,6. Kruskal-Wallis tests were used to compare family history scores. Results: MMRD+/germ-line- individuals had significantly lower median family history scores (MMRpro = 8.1, PREMM 1,2,6 = 7.3) than did LS individuals (MMRpro = 89.8, PREMM 1,2,6 = 26.1, P < 0.0001). Conclusion: MMRD+/germ-line- individuals have less suggestive family histories of LS than individuals with LS. These results imply that MMRD+/germ-line- individuals may not all have LS. This finding highlights the need to determine other causes of MMRD tumors so that these patients and their families can be accurately counseled regarding screening and management.

Original languageEnglish (US)
Pages (from-to)476-484
Number of pages9
JournalGenetics in Medicine
Issue number6
StatePublished - Jun 4 2015

ASJC Scopus subject areas

  • Genetics(clinical)


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