title: Is it all Lynch syndrome?: An assessment of family history in individuals with mismatch repair-deficient tumors.
abstract: OBJECTIVE
  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 PREMM1,2,6. 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, PREMM1,2,6 = 7.3) than did LS individuals (MMRpro = 89.8, PREMM1,2,6 = 26.1, P < 0.0001).
  
  
  CONCLUSIONS
  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.Genet Med 17 6, 476-484.
authors.affiliation: 1] Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [2] Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [3] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Dempsey
authors.affiliation: 1] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA [2] Department of Pathology Administration, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Broaddus
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Y Nancy
authors.initials: YN
authors.lastname: You
authors.affiliation: 1] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA [2] Department of Obstetrics and Gynecology, The University of Texas Health Science Center at Houston, Houston, Texas, USA [3] Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Sarah Jane
authors.initials: SJ
authors.lastname: Noblin
authors.affiliation: 1] Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [2] Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Mork
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Fellman
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Urbauer
authors.affiliation: 1] Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [2] Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [3] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA [4] Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Molly
authors.identifier: 000000016652944X
authors.initials: M
authors.lastname: Daniels
authors.affiliation: 1] Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics; D005190:Family; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018570:Risk Assessment
chemical_list: D048493:Proto-Oncogene Proteins B-raf