title: Novel MC1R variants in Ligurian melanoma patients and controls.
abstract: Several variant forms of the melanocortin-1 receptor gene (MC1R) have been associated with red hair, fair skin and an increased risk for melanoma. Their involvement in melanoma susceptibility is apparently linked both to skin sensitivity and to non-pigmentary pathways. We investigated the frequency of the MC1R variants in the Italian region of Liguria, where the occurrence and penetrance of melanoma are low and primary susceptibility is characterized by prevalence of the CDKN2A c.301G>T [p.G101W] founder mutation. Additionally, we attempted to establish the frequency of the red hair/fair skin phenotype in our region. As predicted by anecdotal evidence, the frequency of red hair/phototype I was very low (0.7%). Screening of 17 red-haired individuals and their red-haired relatives, 207 controls and 214 melanoma patients unselected for hair color but all of Ligurian descent, led to the detection of 8 novel substitutions (c.133T>C [p.F45L], c.248C>T [p.S83L], c.332C>T [p. A111V], c.479G>A [p.R160Q], c.637C>T [p.R213W], c.793G>A [p. V265I], c.923C>T [p. T308M], c.943T>C [p.C315R]), 1 novel deletion (c.520_523delGTC [p.V174del]) and 3 novel synonymous variants (c.366G>C [p. V122V], c.684G>A [p. Q228Q], c.726C>T [p.T241T]). Preliminary genotype/phenotype correlation seems to indicate that other genes involved in the regulation of human pigmentation may mask the recessive action of high-penetrance MC1R alleles, thus determining the low frequency of at-risk phototypes and of incidence and/or penetrance of melanoma in Liguria.
authors.affiliation: Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, 16132, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.forename: Roberto
authors.initials: R
authors.lastname: Cusano
authors.forename: William
authors.initials: W
authors.lastname: Bruno
authors.forename: Francesca
authors.initials: F
authors.lastname: Lantieri
authors.forename: Paola
authors.initials: P
authors.lastname: Origone
authors.forename: Monica
authors.initials: M
authors.lastname: Barile
authors.forename: Sara
authors.initials: S
authors.lastname: Gliori
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Shepherd
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarra
authors.forename: Giovanna Bianchi
authors.initials: GB
authors.lastname: Scarra
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D017720:Molecular Epidemiology / Q000379:methods; D008969:Molecular Sequence Data; D010375:Pedigree; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics
chemical_list: D044102:Receptor, Melanocortin, Type 1