title: MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters.
abstract: The genetic background of cutaneous malignant melanoma (CMM) includes both germ line aberrations in high-penetrance genes, like CDKN2A, and allelic variation in low-penetrance genes like the melanocortin-1 receptor gene, MC1R. Red-hair colour associated MC1R alleles (RHC) have been associated with red hair, fair skin and risk of CMM. We investigated MC1R and CDKN2A variation in relation to phenotype, clinical factors and CMM risk in the Swedish population. The study cohort consisted of sporadic primary melanoma patients, familial melanoma patients and a control group. An allele-dose dependent increase in melanoma risk for carriers of variant MC1R alleles (after adjusting for phenotype), with an elevated risk among familial CMM patients, was observed. This elevated risk was found to be significantly associated with an increased frequency of dysplastic nevi (DN) among familial patients compared to sporadic patients. MC1R variation was found to be less frequent among acral lentiginous melanomas (ALM) and dependent on tumour localisation. No association was found between CDKN2A gene variants and general melanoma risk. Two new variants in the POMC gene were identified in red haired individuals without RHC alleles.
authors.affiliation: Department of Oncology-Pathology, CCK, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. Veronica.Hoiom@ki.se
authors.forename: Veronica
authors.initials: V
authors.lastname: Höiom
authors.forename: Rainer
authors.initials: R
authors.lastname: Tuominen
authors.forename: Max
authors.initials: M
authors.lastname: Käller
authors.forename: Diana
authors.initials: D
authors.lastname: Lindén
authors.forename: Afshin
authors.initials: A
authors.lastname: Ahmadian
authors.forename: Eva
authors.initials: E
authors.lastname: Månsson-Brahme
authors.forename: Suzanne
authors.initials: S
authors.lastname: Egyhazi
authors.forename: Klas
authors.initials: K
authors.lastname: Sjöberg
authors.forename: Joakim
authors.initials: J
authors.lastname: Lundeberg
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D013548:Sweden; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D044102:Receptor, Melanocortin, Type 1; D025803:Tumor Suppressor Protein p14ARF