title: CDKN2A common variants and their association with melanoma risk: a population-based study.
abstract: The population frequencies of the CDKN2A variants remain undetermined. In Poland there are three common variants of CDKN2A: an alanine to threonine substitution (A148T), Nt500c>g and Nt540c>t, which have been detected in other populations. To establish if they are associated with an increased malignant melanoma (MM) risk we did an association study based on genotyping 471 patients with MM and 1,210 random control subjects from the same Polish population. We found a significantly increased frequency of the A148T variant among patients with MM (7.0%) in comparison with the general population (2.9%). The incidence of the A148T variant remained greater in both unselected and familial melanoma subgroups. A statistically significant positive association was seen for unselected MM (odds ratio, 2.529; P = 0.0003), especially in patients diagnosed under 50 years of age (odds ratio, 3.4; P = 0.0002). The A148T carrier population (heterozygous G/A alleles) was more likely to have a relative with malignancy compared with the noncarrier population (57% versus 36%, respectively; P = 0.03). Further examination of the CDKN2A promoter sequence done in 20 melanoma patients with the A148T change (heterozygous G/A alleles) and 20 patients with MM without this alteration identified it was in linkage disequilibrium with a polymorphism in the promoter region at position P-493. We found no statistically significant overrepresentation of the Nt500c>g and the Nt540c>t polymorphisms in the Polish melanoma population. In conclusion, the A148T variant of the CDKN2A gene seems to be associated with an increased risk of development of MM. Additional studies are required to confirm whether this particular change is associated with increased risk of other nonmelanoma malignancies.
authors.affiliation: Departments of Genetics and Pathology, International Hereditary Cancer Center and Dermatology and Venerology, Pomeranian Medical University, Połabska 4, 70-115 Szczecin, Poland. debniak@wp.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rozmiarek
authors.forename: Bogusław
authors.initials: B
authors.lastname: Debniak
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Załuga
authors.forename: Romuald
authors.initials: R
authors.lastname: Maleszka
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged