Purpose:The aim of this study was to assess whether differences in frequency and phenotype of APC and MUTYH mutations exist among racially/ethnically diverse populations.Methods:We studied 6,169 individuals with a personal and/or family history of colorectal cancer (CRC) and polyps. APC testing involved full sequencing/large rearrangement analysis (FS/LRA); MUTYH involved "panel testing" (for Y165C, G382D mutations) or FS/LRA performed by Myriad Genetics, a commercial laboratory. Subjects were identified as Caucasian, Asian, African American (AA), or other. Statistical tests included χ 2, Fisher's exact test, analysis of variance, and z approximation.Results:Among participants, 17.5% had pathogenic APC mutations and 4.8% were biallelic MUTYH carriers. With regard to race/ethnicity, 18% were non-Caucasian, with >100 adenomas and younger ages at adenoma or CRC diagnosis (P < 0.0001) than Caucasians. The overall APC mutation rate was higher in Asians, AAs, and others as compared with Caucasians (25.2, 30.9, 24, and 15.5%, respectively; P < 0.0001) but was similar in all groups when adjusted for polyp burden. More MUTYH biallelic carriers were Caucasian or other than Asian or AA (5, 7, 2.7, and 0.3%, respectively; P < 0.0001). Among Caucasians, 5% were biallelic carriers identified by panel testing versus 2% identified by sequencing/large rearrangement analysis (LRA) (P = 0.002). Among non-Caucasians, 3% undergoing panel testing were biallelic carriers versus 10% identified by sequencing/LRA (P < 0.0002).Conclusion:Non-Caucasians undergo genetic testing at more advanced stages of polyposis and/or are younger at CRC/polyp diagnosis. Restricted MUTYH analysis may miss significant numbers of biallelic carriers, particularly in non-Caucasians.

familial adenomatous polyposis, genetic testing, MUTYH-associated polyposis, phenotype, race
dx.doi.org/10.1038/gim.2014.199, hdl.handle.net/1765/91931
Genetics in Medicine
Department of Public Health

Inra, J.A, Steyerberg, E.W, Grover, S, McFarland, A, Syngal, S, & Kastrinos, F. (2015). Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169 individuals undergoing genetic testing. Genetics in Medicine, 17(10), 815–821. doi:10.1038/gim.2014.199