title: Evaluation of PAX3 genetic variants and nevus number.
abstract: The presence of a high nevus number is the strongest phenotypic predictor of melanoma risk. Here, we describe the results of a three-stage study directed at identifying risk variants for the high nevus phenotype. At the first stage, 263 melanoma cases from Barcelona were genotyped for 223 single-nucleotide polymorphisms (SNPs) in 39 candidate genes. Seven SNPs in the PAX3 gene were found to be significantly associated with nevus number under the additive model. Next, the associations for seven PAX3 variants were evaluated in 1217 melanoma cases and 475 controls from Leeds; and in 3054 healthy twins from TwinsUK. Associations with high nevus number were detected for rs6754024 (P values < 0.01) in the Barcelona and Leeds datasets and for rs2855268 (P values < 0.01) in the Barcelona and the TwinsUK sets. Associations (P values < 0.001) in the opposite direction were detected for rs7600206 and rs12995399 in the Barcelona and TwinsUK sets. This study suggests that SNPs in PAX3 are associated with nevus number, providing support for PAX3 as a candidate nevus gene. Further studies are needed to examine the role of PAX3 in melanoma susceptibility.
authors.affiliation: Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain. zigheog@gmail.com
authors.forename: Zighereda
authors.initials: Z
authors.lastname: Ogbah
authors.forename: Celia
authors.initials: C
authors.lastname: Badenas
authors.forename: Mark
authors.initials: M
authors.lastname: Harland
authors.forename: Joan A
authors.initials: JA
authors.lastname: Puig-Butille
authors.forename: Fay
authors.initials: F
authors.lastname: Elliot
authors.forename: Nuria
authors.initials: N
authors.lastname: Bonifaci
authors.forename: Elisabet
authors.initials: E
authors.lastname: Guino
authors.forename: Julie
authors.initials: J
authors.lastname: Randerson-Moor
authors.forename: May
authors.initials: M
authors.lastname: Chan
authors.forename: Mark M
authors.initials: MM
authors.lastname: Iles
authors.forename: Daniel
authors.initials: D
authors.lastname: Glass
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Brown
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrera
authors.forename: Isabel
authors.initials: I
authors.lastname: Kolm
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Josep
authors.initials: J
authors.lastname: Malvehy
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
authors.forename: Miquel A
authors.initials: MA
authors.lastname: Pujana
authors.forename: Tim
authors.initials: T
authors.lastname: Bishop
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009506:Nevus / Q000235:genetics* / Q000473:pathology*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D013030:Spain; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors
keywords: PAX3; SNP; melanoma; nevus; susceptibility