title: Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants.
abstract: To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, P<0.001). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% CI 2.15-7.38, P<0.001) that of carriers of one variant (OR 1.98, 95% CI 1.26-3.11, P=0.003). After stratification according to the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia. aija.ozola@biomed.lu.lv
authors.forename: Aija
authors.initials: A
authors.lastname: Ozola
authors.forename: Kristīne
authors.initials: K
authors.lastname: Azarjana
authors.forename: Simona
authors.initials: S
authors.lastname: Doniņa
authors.forename: Guna
authors.initials: G
authors.lastname: Proboka
authors.forename: Ilona
authors.initials: I
authors.lastname: Mandrika
authors.forename: Ramona
authors.initials: R
authors.lastname: Petrovska
authors.forename: Ingrīda
authors.initials: I
authors.lastname: Cēma
authors.forename: Olita
authors.initials: O
authors.lastname: Heisele
authors.forename: Ludmila
authors.initials: L
authors.lastname: Eņģele
authors.forename: Baiba
authors.initials: B
authors.lastname: Streinerte
authors.forename: Dace
authors.initials: D
authors.lastname: Pjanova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007844:Latvia; D015810:Linkage Disequilibrium; D008297:Male; D008545:Melanoma; D018613:Microscopy, Confocal; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D044102:Receptor, Melanocortin, Type 1; D049452:Green Fluorescent Proteins; D000242:Cyclic AMP