title: Genome-wide linkage analysis of Swedish families to identify putative susceptibility loci for cutaneous malignant melanoma.
abstract: Cutaneous malignant melanoma is a clinically and genetically heterogeneous disorder which is caused by an interaction between hereditary and environmental factors. In Sweden, a small portion of the inherited susceptibility is explained by the presence of germline mutations in the tumor suppressor gene CDKN2A. But still, the genetic background of melanoma susceptibility is largely unknown. Here, we conducted a genome-wide linkage scan on melanoma-prone families using high-density single-nucleotide polymorphisms (SNPs) arrays to identify novel melanoma susceptibility genes. We investigated 35 families of Swedish origin without CDKN2A mutations. Nonparametric and parametric multipoint linkage analyses were performed. After removal of SNPs in strong linkage disequilibrium, the strongest evidence of linkage was detected on chromosome 17p11-12 (logarithm (base 10) of odds (LOD) scores of 2.76) using parametric linkage analysis assuming a dominant trait with full penetrance. Analyses were also performed on a subset of families with low age at diagnosis (mean age ≤ 47 years), to obtain a more homogenous subset. This subgroup analysis based on 22 families yielded suggestive evidence of linkage to the chromosomal regions 11p12-p11 and 18q22 (multipoint LOD scores of 2.10 and 2.02, respectively). Also, the 17p region that was detected in the complete family set showed suggestive linkage in this cohort (multipoint LOD scores of 2.01). Our data suggest that these chromosomal regions, 17p12-p11 in particular as it was present in both analyses, may harbor genes involved in the susceptibility of malignant melanoma in the Swedish population.
authors: Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden. Veronica.Hoiom@ki.se
authors: Veronica
authors: V
authors: Höiom
authors: Rainer
authors: R
authors: Tuominen
authors: Johan
authors: J
authors: Hansson
mesh_terms: D000328:Adult; D002886:Chromosomes, Human, Pair 17; D005192:Family Health; D005260:Female; D019942:Genes, p16; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics*; D013548:Sweden