title: Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.
abstract: The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.
authors.affiliation: Unite INSERM 535 'Génétique Epidémiologique et Structure des Populations Humaines', Hôpital Paul Brousse, Villejuif, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Jannot
authors.forename: Roubila
authors.initials: R
authors.lastname: Meziani
authors.forename: Guylene
authors.initials: G
authors.lastname: Bertrand
authors.forename: Benedicte
authors.initials: B
authors.lastname: Gérard
authors.forename: Vincent
authors.initials: V
authors.lastname: Descamps
authors.forename: Alain
authors.initials: A
authors.lastname: Archimbaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Picard
authors.forename: Laurence
authors.initials: L
authors.lastname: Ollivaud
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset-Seguin
authors.forename: Delphine
authors.initials: D
authors.lastname: Kerob
authors.forename: Guy
authors.initials: G
authors.lastname: Lanternier
authors.forename: Celeste
authors.initials: C
authors.lastname: Lebbe
authors.forename: P
authors.initials: P
authors.lastname: Saiag
authors.forename: Beatrice
authors.initials: B
authors.lastname: Crickx
authors.forename: Françoise
authors.initials: F
authors.lastname: Clerget-Darpoux
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
authors.lastname: Melan-Cohort
mesh_terms: D000328:Adult; D000368:Aged; D005127:Eye Color / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012044:Regression Analysis; D012878:Skin Neoplasms / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D044102:Receptor, Melanocortin, Type 1