Tags

Type your tag names separated by a space and hit enter

Performance of Lynch syndrome predictive models in a multi-center US referral population.
Am J Gastroenterol. 2011 Oct; 106(10):1822-7; quiz 1828.AJ

Abstract

OBJECTIVES

Lynch syndrome is the most common cause of inherited colorectal cancer (CRC) and is due to germline mutations in mismatch repair (MMR) genes. Early Lynch syndrome diagnosis and appropriate CRC surveillance improves mortality. Traditional qualitative clinical criteria including Amsterdam and Bethesda guidelines may miss mutation carriers. Recently, quantitative predictive models including MMRPredict, PREMM(1,2,6), and MMRPro were developed to facilitate diagnosis. However, these models remain to be externally validated in the United States. Therefore, we evaluated the test characteristics of Lynch syndrome predictive models in a tertiary referral group at two US academic centers.

METHODS

We retrospectively collected data on 230 consecutive individuals who underwent genetic testing for MMR gene mutations at the University of Chicago and University of California at San Francisco's Cancer Risk Clinics. Each individual's risk of mutation was examined using MMRPredict, PREMM(1,2,6), and MMRPro. Amsterdam and Bethesda criteria were also determined. Testing characteristics were calculated for each of the models.

RESULTS

We included 230 individuals in the combined cohort. In all, 113 (49%) probands were MMR mutation carriers. Areas under the receiver operator characteristic curves were 0.76, 0.78, and 0.82 for MMRPredict, PREMM(1,2,6), and MMRPro, respectively. While similar in overall performance, our study highlights unique test characteristics of these three quantitative models including comparisons of sensitivity and specificity. Moreover, we identify characteristics of mutation carriers who were missed by each model.

CONCLUSIONS

Overall, all three Lynch syndrome predictive models performed comparably in our multi-center US referral population. These results suggest that Lynch syndrome predictive models can be used to screen for MMR mutation carriers and can provide improved test characteristics compared with traditional clinical criteria. Identification of MMR mutation carriers is paramount as appropriate screening can prevent CRC mortality in this high-risk group.

Authors+Show Affiliations

Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, Illinois 60637, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21747416

Citation

Khan, Omar, et al. "Performance of Lynch Syndrome Predictive Models in a Multi-center US Referral Population." The American Journal of Gastroenterology, vol. 106, no. 10, 2011, pp. 1822-7; quiz 1828.
Khan O, Blanco A, Conrad P, et al. Performance of Lynch syndrome predictive models in a multi-center US referral population. Am J Gastroenterol. 2011;106(10):1822-7; quiz 1828.
Khan, O., Blanco, A., Conrad, P., Gulden, C., Moss, T. Z., Olopade, O. I., Kupfer, S. S., & Terdiman, J. (2011). Performance of Lynch syndrome predictive models in a multi-center US referral population. The American Journal of Gastroenterology, 106(10), 1822-7; quiz 1828. https://doi.org/10.1038/ajg.2011.200
Khan O, et al. Performance of Lynch Syndrome Predictive Models in a Multi-center US Referral Population. Am J Gastroenterol. 2011;106(10):1822-7; quiz 1828. PubMed PMID: 21747416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Performance of Lynch syndrome predictive models in a multi-center US referral population. AU - Khan,Omar, AU - Blanco,Amie, AU - Conrad,Peggy, AU - Gulden,Cassandra, AU - Moss,Tovah Z, AU - Olopade,Olufunmilayo I, AU - Kupfer,Sonia S, AU - Terdiman,Jonathan, Y1 - 2011/07/12/ PY - 2011/7/13/entrez PY - 2011/7/13/pubmed PY - 2011/12/13/medline SP - 1822-7; quiz 1828 JF - The American journal of gastroenterology JO - Am J Gastroenterol VL - 106 IS - 10 N2 - OBJECTIVES: Lynch syndrome is the most common cause of inherited colorectal cancer (CRC) and is due to germline mutations in mismatch repair (MMR) genes. Early Lynch syndrome diagnosis and appropriate CRC surveillance improves mortality. Traditional qualitative clinical criteria including Amsterdam and Bethesda guidelines may miss mutation carriers. Recently, quantitative predictive models including MMRPredict, PREMM(1,2,6), and MMRPro were developed to facilitate diagnosis. However, these models remain to be externally validated in the United States. Therefore, we evaluated the test characteristics of Lynch syndrome predictive models in a tertiary referral group at two US academic centers. METHODS: We retrospectively collected data on 230 consecutive individuals who underwent genetic testing for MMR gene mutations at the University of Chicago and University of California at San Francisco's Cancer Risk Clinics. Each individual's risk of mutation was examined using MMRPredict, PREMM(1,2,6), and MMRPro. Amsterdam and Bethesda criteria were also determined. Testing characteristics were calculated for each of the models. RESULTS: We included 230 individuals in the combined cohort. In all, 113 (49%) probands were MMR mutation carriers. Areas under the receiver operator characteristic curves were 0.76, 0.78, and 0.82 for MMRPredict, PREMM(1,2,6), and MMRPro, respectively. While similar in overall performance, our study highlights unique test characteristics of these three quantitative models including comparisons of sensitivity and specificity. Moreover, we identify characteristics of mutation carriers who were missed by each model. CONCLUSIONS: Overall, all three Lynch syndrome predictive models performed comparably in our multi-center US referral population. These results suggest that Lynch syndrome predictive models can be used to screen for MMR mutation carriers and can provide improved test characteristics compared with traditional clinical criteria. Identification of MMR mutation carriers is paramount as appropriate screening can prevent CRC mortality in this high-risk group. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/21747416/Performance_of_Lynch_syndrome_predictive_models_in_a_multi_center_US_referral_population_ L2 - https://Insights.ovid.com/pubmed?pmid=21747416 DB - PRIME DP - Unbound Medicine ER -