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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. (English) Zbl 1071.62099

Summary: Microsatellite instability (MSI) testing is a common screening procedure used to identify families that may harbor mutations of a mismatch repair (MMR) 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 MMR genes is critical in genetic counseling and colorectal cancer prevention. Several studies published results of both MSI and mutation analysis on the same subjects. 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 0.81 (0.73-0.89). 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 address these challenges in the context of a Bayesian meta-analytic implementation of the S. L. Hui and S. D. Walter design [Biometrics 36, 167–171 (1980; Zbl 0436.62093)], tailored to account for various forms of incomplete data. Posterior inference is handled via a Gibbs sampler.

MSC:

62P10 Applications of statistics to biology and medical sciences; meta analysis

Citations:

Zbl 0436.62093
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