The low prevalence of the BRAF V600E mutation in colorectal cancers (CRCs) in Chinese populations has stimulated concern about the efficacy of BRAF mutation analysis for Lynch syndrome (LS) screening.
In total, 169 of 4104 consecutive CRC patients with absent MLH1 staining were analyzed to compare the utility of the BRAF V600E mutation testing with MLH1 promoter methylation analysis in the Chinese population. Germline genetic testing was performed in patients with wild-type BRAF/methylated MLH1.
Compared with BRAF genotyping, the use of MLH1 methylation testing alone to evaluate patients with MLH1 deficiency reduced referral rates for germline testing by 1.8-fold (82.8% vs. 47.1%). However, 6 patients harboring MLH1 promoter methylation were verified to have LS through germline genetic testing. It is notable that all 6 patients had a family history of CRC in at least 1 first-degree relative (FDR) or second-degree relative (SDR). The combination of MLH1 promoter methylation analysis and a family history of CRC could preclude significantly more patients from germline genetic testing than from BRAF mutation testing alone (45.5% vs. 17.2%, p<0.001) and decrease the number of misdiagnosed LS patients with MLH1 promoter methylation.
The combination of a family history of CRC with MLH1 promoter methylation analysis showed better performance than BRAF mutation testing in the selection of patients in the Chinese population for germline genetic testing.

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