title: Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans.
abstract: OBJECTIVE
  Lynch syndrome, the commonest hereditary colorectal cancer syndrome, is caused by germline mutations in mismatch repair (MMR) genes. Three recently developed prediction models for MMR gene mutations based on family history and clinical features (MMRPredict, PREMM(1,2,6), and MMRPro) have been validated only in Western countries. In this study, we propose validating these prediction models in the Korean population.
  
  
  METHODS
  We collected MMR gene analysis data from 188 individuals in the Korean Hereditary Tumor Registry. The probability of gene mutation was calculated using three prediction models, and the overall diagnostic value of each model compared using receiver operator characteristic (ROC) curves and area under the ROC curve (AUC). Quantitative test characteristics were calculated at sensitivities of 90%, 95%, and 98%.
  
  
  RESULTS
  Of the individuals analyzed, 101 satisfied Amsterdam criteria II, and 87 were suspected hereditary nonpolyposis colorectal cancer. MMR mutations were identified in 62 of the 188 subjects (33.0%). All three prediction models showed a poor predictive value of AUC (MMRPredict, 0.683; PREMM(1,2,6), 0.709; MMRPro, 0.590). Within the range of acceptable sensitivity (> 90%), PREMM(1,2,6) demonstrated higher specificity than the other models.
  
  
  CONCLUSIONS
  In the Korean population, overall predictive values of the three models (MMRPredict, PREMM(1,2,6), MMRPro) for MMR gene mutations are poor, compared with their performance in Western populations. A new prediction model is therefore required for the Korean population to detect MMR mutation carriers, reflecting ethnic differences in genotype-phenotype associations.
authors.affiliation: Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.|Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Myong Hoon
authors.initials: MH
authors.lastname: Ihn
authors.affiliation: Department of Surgery, Chung Hospital, Seongnam, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Heung-Kwon
authors.initials: HK
authors.lastname: Oh
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jae Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Public Health Science, Seoul National University, Seoul, Korea.
authors.forename: Sungho
authors.initials: S
authors.lastname: Won
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
mesh_terms: D019540:Area Under Curve; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D053843:DNA Mismatch Repair; D018095:Germ-Line Mutation; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D012680:Sensitivity and Specificity
keywords: Genetic testing; Hereditary nonpolyposis colorectal neoplasms; Mismatch repair gene; Prediction model