title: Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC).
abstract: BACKGROUND
  Melanocytic naevi are an important risk factor for melanoma. Naevi with distinct dermoscopic patterns can differ in size, distribution and host pigmentation characteristics.
  
  
  OBJECTIVE
  We examined MC1R and 85 other candidate loci in a cohort of children to test the hypothesis that the development and dermoscopic type of naevi are modulated by genetic variants.
  
  
  METHODS
  Buccal DNAs were obtained from a cohort of 353 fifth graders (mean age 10·4 years). Polymorphisms were chosen based on a known or anticipated role in naevi and melanoma. Associations between single-nucleotide polymorphisms (SNPs) and baseline naevus count were determined by multivariate regression adjusting for sex, race/ethnicity and sun sensitivity. Dermoscopic images were available for 853 naevi from 290 children. Associations between SNPs and dermoscopic patterns were determined by polytomous regression.
  
  
  RESULTS
  Four SNPs were significantly associated with increasing (IRF4) or decreasing (PARP1, CDK6 and PLA2G6) naevus count in multivariate shrinkage analyses with all SNPs included in the model; IRF4 rs12203952 showed the strongest association with log naevus count (relative risk 1·56, P < 0·001). Using homogeneous naevi as the reference, IRF4 rs12203952 and four other SNPs in TERT, CDKN1B, MTAP and PARP1 were associated with either globular or reticular dermoscopic patterns (P < 0·05).
  
  
  CONCLUSIONS
  Our results provide evidence that subsets of naevi defined by dermoscopic patterns differ in their associations with germline genotypes and support the hypothesis that dermoscopically defined subsets of naevi are biologically distinct. These results require confirmation in larger cohorts. If confirmed, these findings will improve the current knowledge of naevogenesis and assist in the identification of individuals with high-risk phenotypes.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, U.S.A.
authors.forename: I
authors.initials: I
authors.lastname: Orlow
authors.forename: J M
authors.initials: JM
authors.lastname: Satagopan
authors.forename: M
authors.initials: M
authors.lastname: Berwick
authors.forename: H L
authors.initials: HL
authors.lastname: Enriquez
authors.forename: K A M
authors.initials: KA
authors.lastname: White
authors.forename: K
authors.initials: K
authors.lastname: Cheung
authors.forename: S W
authors.initials: SW
authors.lastname: Dusza
authors.forename: S A
authors.initials: SA
authors.lastname: Oliveria
authors.forename: M A
authors.initials: MA
authors.lastname: Marchetti
authors.forename: A
authors.initials: A
authors.lastname: Scope
authors.forename: A A
authors.initials: AA
authors.lastname: Marghoob
authors.forename: A C
authors.initials: AC
authors.lastname: Halpern
mesh_terms: D000483:Alleles; D002648:Child; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D046169:Dermoscopy / Q000379:methods; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D054522:Group VI Phospholipases A2 / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D008297:Male; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects; D000099218:Interferon Regulatory Factor-4
chemical_list: D051361:Cyclin-Dependent Kinase 6; D054522:Group VI Phospholipases A2; D050835:Interferon Regulatory Factors; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D044102:Receptor, Melanocortin, Type 1; D000099218:Interferon Regulatory Factor-4; C499320:PARP1 protein, human; C495911:CDK6 protein, human; C516475:PLA2G6 protein, human