Cancer Res Treat.  2016 Apr;48(2):668-675. 10.4143/crt.2014.288.

Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans

• Lee SY
• Kim DW
• Shin YK
• Ihn MH
• Lee SM
• Oh HK
• Ku JL
• Jeong SY
• Lee JB
• Ahn S
• Won S
• Kang SB

• KMID: 2454345
• DOI: http://doi.org/10.4143/crt.2014.288

Abstract

PURPOSE
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, PREMM1,2,6, and MMRPro) have been validated only in Western countries. In this study, we propose validating these prediction models in the Korean population.
MATERIALS AND 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; PREMM1,2,6, 0.709; MMRPro, 0.590). Within the range of acceptable sensitivity (> 90%), PREMM1,2,6 demonstrated higher specificity than the other models.
CONCLUSION
In the Korean population, overall predictive values of the three models (MMRPredict, PREMM1,2,6, 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.

Keyword

Hereditary nonpolyposis colorectal neoplasms; Prediction model; Genetic testing; Mismatch repair gene

MeSH Terms

Area Under Curve
Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis
DNA Mismatch Repair*
Genetic Association Studies
Genetic Testing
Germ-Line Mutation
Humans
ROC Curve
Sensitivity and Specificity

Figure

• 

  Fig. 1. Distribution of risk scores of mismatch repair (MMR) gene mutations calculated for the three prediction models. (A) MMRPredict. (B) PREMM1,2,6. (C) MMRPro. The models show different distribution patterns and skewness.

• 

  Fig. 2. Receiver-operator characteristic curves for MMRPredict, PREMM1,2,6, and MMRPro. Area under the ROC curves (AUCs) for each model are shown.

Reference

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