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identified in patients from families that met the Amsterdam Criteria (AC I/II), whereas 3 mutations were found in patients from families that were AC I/II negative. The modified likelihood for a germline mutation (+LRmod )i n an AC I/II patient was 1.56 (95% CI: 0.47 - 5.18) and the modified negative likelihood ratio (-LRmod )f or ap atient not meeting the AC I/II criteria was 0.81 (95% CI: 0.39 1.69). We quantified the meaning of the AC I/II criteria to guide clinical choices about genetic testing in MSS tumors by multiplying the pretest odds by the +LRmod and the -LRmod. The probability of a mutation was modified from a baseline of 11.4% to 16.7% in AC I/II families, compared to 9.4% in AC I/II-negative families. Conclusions Germline MMR testing in high risk patients with MSS colorectal tumors identifies mutations in a small, but meaningful proportion of patients. The diagnostic yield is dependent on the strength of the family history. Modified likelihood ratios can be helpful to quantify the probability of a positive gene test for Lynch Syndrome, and can be applied to pre-test probabilities derived from clinical models.

Estimating probability of germline mismatch repair mutations in colorectal cancer patients with microsatellite stable tumors