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Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans.
Cancer Res Treat. 2016 Apr; 48(2):668-75.CR

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, 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.

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; 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.

CONCLUSION

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+Show Affiliations

Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.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.Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.Department of Surgery, Chung Hospital, Seongnam, Korea.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.Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.Department of Public Health Science, Seoul National University, Seoul, Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

26044159

Citation

Lee, Soo Young, et al. "Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans." Cancer Research and Treatment : Official Journal of Korean Cancer Association, vol. 48, no. 2, 2016, pp. 668-75.
Lee SY, Kim DW, Shin YK, et al. Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans. Cancer Res Treat. 2016;48(2):668-75.
Lee, S. Y., Kim, D. W., Shin, Y. K., Ihn, M. H., Lee, S. M., Oh, H. K., Ku, J. L., Jeong, S. Y., Lee, J. B., Ahn, S., Won, S., & Kang, S. B. (2016). Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans. Cancer Research and Treatment : Official Journal of Korean Cancer Association, 48(2), 668-75. https://doi.org/10.4143/crt.2014.288
Lee SY, et al. Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans. Cancer Res Treat. 2016;48(2):668-75. PubMed PMID: 26044159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation of Prediction Models for Mismatch Repair Gene Mutations in Koreans. AU - Lee,Soo Young, AU - Kim,Duck-Woo, AU - Shin,Young-Kyoung, AU - Ihn,Myong Hoon, AU - Lee,Sung Min, AU - Oh,Heung-Kwon, AU - Ku,Ja-Lok, AU - Jeong,Seung-Yong, AU - Lee,Jae Bong, AU - Ahn,Soyeon, AU - Won,Sungho, AU - Kang,Sung-Bum, Y1 - 2015/06/05/ PY - 2014/10/15/received PY - 2015/05/05/accepted PY - 2015/6/6/entrez PY - 2015/6/6/pubmed PY - 2018/3/9/medline KW - Genetic testing KW - Hereditary nonpolyposis colorectal neoplasms KW - Mismatch repair gene KW - Prediction model SP - 668 EP - 75 JF - Cancer research and treatment : official journal of Korean Cancer Association JO - Cancer Res Treat VL - 48 IS - 2 N2 - 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, 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. 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; 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. CONCLUSION: 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. SN - 2005-9256 UR - https://www.unboundmedicine.com/medline/citation/26044159/Validation_of_Prediction_Models_for_Mismatch_Repair_Gene_Mutations_in_Koreans_ L2 - https://dx.doi.org/10.4143/crt.2014.288 DB - PRIME DP - Unbound Medicine ER -