Accuracy of MSI Testing in Predicting Germline Mutations of MSH2 and MLH1: A Case Study in Bayesian Meta-Analysis of Diagnostic Tests Without a Gold Standard

Sining Chen, Patrice Watson and Giovanni Parmigiani
Additional contact information
Sining Chen: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
Patrice Watson: Hereditary Cancer Institute, Creighton University School of Medicine, Omaha, NE
Giovanni Parmigiani: Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health

No 1043, Johns Hopkins University Dept. of Biostatistics Working Paper Series from Berkeley Electronic Press

Abstract: Microsatellite instability (MSI) testing is a common screening procedure used to identify families that may harbor mutations of a mismatch repair gene and therefore may be at high risk for hereditary colorectal cancer. A reliable estimate of sensitivity and specificity of MSI for detecting germline mutations of mismatch repair genes is critical in genetic counseling and colorectal cancer prevention. Several studies published results of both MSI and mutation analysis on the same subjects. In this article we perform a meta-analysis of these studies and obtain estimates that can be directly used in counseling and screening. In particular we estimate the sensitivity of MSI for detecting mutations of MSH2 and MLH1 to be 0.78 (0.69--0.86). Statistically, challenges arise from the following: a) traditional mutation analysis methods used in these studies cannot be considered a gold standard for the identification of mutations; b) studies are heterogeneous in both the design and the populations considered; and c) studies may include different patterns of missing data resulting from partial testing of the populations sampled. We addressed these challenges in the context of a Bayesian meta-analytic implementation of the Hui-Walter design, designed to account for various forms of incomplete data. Posterior inference are handled via a Gibbs sampler.

Keywords: Sensitivity; Specificity; Diagnostic test; Microsatellite instability (MSI); Hereditary nonpolyposis colorectal cancer (HNPCC) (search for similar items in EconPapers)
Date: 2004-07-11
Note: oai:bepress.com:jhubiostat-1043
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
http://www.bepress.com/cgi/viewcontent.cgi?article=1043&context=jhubiostat (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:bep:jhubio:1043

Access Statistics for this paper

More papers in Johns Hopkins University Dept. of Biostatistics Working Paper Series from Berkeley Electronic Press
Bibliographic data for series maintained by Christopher F. Baum ().