03044nas a2200625   4500000000100000008004100001653001000042653001100052653001100063653000900074653000900083653001600092653001800108653001400126653001300140653002600153653001300179653002200192653001300214653001400227653003400241653003500275653001900310100001400329700001200343700001700355700002000372700001900392700001600411700001700427700002000444700001400464700002200478700001900500700001100519700001600530700001600546700002200562700002000584700001800604700002000622700001900642700001600661700001600677700001500693700001700708700001500725700002100740700002000761245009900781300001400880490000800894520150200902022001402404       2017                            d10aAdult10aFemale10aHumans10aAged10aMale10aMiddle Aged10aUnited States10aAustralia10aGenotype10aGTP Phosphohydrolases10aMelanoma10aMembrane Proteins10aMutation10aPhenotype10aProto-Oncogene Proteins B-raf10aReceptor, Melanocortin, Type 110aSkin Neoplasms1 aGroup GEM1 aDwyer T1 aThomas Nancy1 aEdmiston Sharon1 aKanetsky Peter1 aBusam Klaus1 aKricker Anne1 aArmstrong Bruce1 aCust Anne1 aAnton-Culver Hoda1 aGruber Stephen1 aLuo Li1 aOrlow Irene1 aReiner Anne1 aGallagher Richard1 aZanetti Roberto1 aRosso Stefano1 aSacchetto Lidia1 aParrish Eloise1 aHao Honglin1 aGibbs David1 aFrank Jill1 aOllila David1 aBegg Colin1 aBerwick Marianne1 aConway Kathleen00aAssociations of MC1R Genotype and Patient Phenotypes with BRAF and NRAS Mutations in Melanoma.  a2588-25980 v1373 a<p>
Associations of MC1R with BRAF mutations in melanoma have been inconsistent between studies. We sought to determine for 1,227 participants in the international population-based Genes, Environment, and Melanoma (GEM) study whether MC1R and phenotypes were associated with melanoma BRAF/NRAS subtypes. We used logistic regression adjusted by age, sex, and study design features and examined effect modifications. BRAFwere associated with younger age, blond/light brown hair, increased nevi, and less freckling, and NRASwith older age relative to the wild type (BRAF/NRAS) melanomas (all P &lt; 0.05). Comparing specific BRAF subtypes to the wild type, BRAF V600E was associated with younger age, blond/light brown hair, and increased nevi and V600K with increased nevi and less freckling (all P &lt; 0.05). MC1R was positively associated with BRAF V600E cases but only among individuals with darker phototypes or darker hair (P&lt; 0.05) but inversely associated with BRAF V600K (P&nbsp;= 0.006) with no significant effect modification by phenotypes. These results support distinct etiologies for BRAF V600E, BRAF V600K, NRAS, and wild-type melanomas. MC1R's associations with BRAF V600E cases limited to individuals with darker phenotypes indicate that MC1R genotypes specifically provide information about BRAF V600E melanoma risk in those not considered high risk based on phenotype. Our results also suggest that melanin pathways deserve further study in BRAF V600E melanomagenesis.
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  a1523-1747