Genes Determining Nevus Count and Dermoscopic Appearance in Australian Melanoma Cases and Controls

Published:August 15, 2019DOI:https://doi.org/10.1016/j.jid.2019.05.032
      Total body nevus counts (TNC) is a highly heritable trait, with twin studies estimating that 60% to 70% of its variance is explained by genetic factors (
      • Lee S.
      • Duffy D.L.
      • McClenahan P.
      • Lee K.J.
      • McEniery E.
      • Burke B.
      • et al.
      Heritability of naevus patterns in an adult twin cohort from the Brisbane Twin Registry: a cross-sectional study.
      ). Polymorphisms within IRF4, MTAP, PLA2G6, and MITF have been shown to strongly influence TNC, and many other nevus-associated genes have been recognized (
      • Duffy D.L.
      • Zhu G.
      • Li X.
      • Sanna M.
      • Iles M.M.
      • Jacobs L.C.
      • et al.
      Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.
      ). Dermoscopy has allowed the recognition of distinct morphological classes of nevi, including reticular, globular, and homogenous and/or complex, that tightly correlate with histopathological subtypes (
      • Tan J.M.
      • Tom L.N.
      • Soyer H.P.
      • Stark M.S.
      Defining the Molecular Genetics of dermoscopic naevus patterns.
      ). There has been great interest in the clinical presentation (
      • Suh K.Y.
      • Bolognia J.L.
      Signature nevi.
      ), body site density (
      • Bataille V.
      • Bishop J.A.
      • Sasieni P.
      • Swerdlow A.J.
      • Pinney E.
      • Griffiths K.
      • et al.
      Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: a case-control study.
      ,
      • Blake T.
      • McClenahan P.
      • Duffy D.
      • Schaider H.
      • McEniery E.
      • Soyer H.P.
      Distribution analyses of acquired melanocytic naevi on the trunk.
      ), dermoscopic growth pattern, and anatomical distribution of nevi (
      • Bajaj S.
      • Dusza S.W.
      • Marchetti M.A.
      • Wu X.
      • Fonseca M.
      • Kose K.
      • et al.
      Growth-curve modeling of nevi with a peripheral globular pattern.
      ,
      • Fonseca M.
      • Marchetti M.A.
      • Chung E.
      • Dusza S.W.
      • Burnett M.E.
      • Marghoob A.A.
      • et al.
      Cross-sectional analysis of the dermoscopic patterns and structures of melanocytic naevi on the back and legs of adolescents.
      ,
      • Marchetti M.A.
      • Kiuru M.H.
      • Busam K.J.
      • Marghoob A.A.
      • Scope A.
      • Dusza S.W.
      • et al.
      Melanocytic naevi with globular and reticular dermoscopic patterns display distinct BRAF V600E expression profiles and histopathological patterns.
      ) in relation to the cutaneous melanoma (CM) risk (
      • Ribero S.
      • Zugna D.
      • Osella-Abate S.
      • Glass D.
      • Nathan P.
      • Spector T.
      • et al.
      Prediction of high naevus count in a healthy UK population to estimate melanoma risk.
      ). In this study, we test the association between the number of nevi of each morphology and melanoma risk and whether known nevus loci predispose to particular nevus morphologies in a genome-wide association study of melanoma cases and controls within the Brisbane Nevus Morphology Study (BNMS).

      Abbreviations:

      BNMS ( Brisbane Nevus Morphology Study), CI ( confidence interval), CM ( cutaneous melanoma), OR ( Odds Ratio), SNP ( single nucleotide polymorphism), TNC ( total nevus count)
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