Variants at chromosome 20 (ASIP locus) and melanoma risk.

Abstract

Agouti signaling protein (ASIP) locus on chromosome 20q11 is implicated, as shown by genome-wide association studies, in phenotype variation and melanoma risk. We genotyped 837 melanoma cases and 1,154 controls for 21 single nucleotide polymorphisms (SNPs) informative for 495 polymorphisms at the locus. Our data showed an increased risk of melanoma (odds ratio [OR] 1.27, 95% confidence interval [95% CI] 1.03-1.57) in carriers of the rs4911414 variant, located 120 kb upstream of ASIP. The main effect of rs4911414, as reported previously, was in tandem with a 10 kb adjacent polymorphism rs1015362; two constituted risk-associated haplotype/diplotype. Except for rs1015363, none of the 12 tagging SNPs, genotyped to cover 239.9 kb region with polymorphisms linked to rs4911414 and rs1015362, were associated with melanoma. Our data confirmed a previous association of melanoma risk (OR 1.82, 95% CI 1.37-2.41) with rs4911442, located in intron 5 of the nuclear receptor coactivator 6 (NCOA6) gene. The rs910871, one of the six variants, genotyped to cover NCOA6, showed an association with melanoma risk (OR 1.33, 95% CI 1.04-1.70). Both, rs4911442 and rs910871 were in moderate linkage with a, previously reported, risk-associated rs910873 polymorphism. A haplotype from the variants within NCOA6 showed an association with risk of melanoma (OR 1.49, 95% CI 1.17-1.88). Interaction between risk-associated polymorphisms and previously genotyped melanocortin receptor 1 (MC1R) variants, in our study, was not statistically significant. Nevertheless, the carriers of the variant alleles over the background of MC1R variants were at a higher risk than the carriers not enriched for MC1R variants. Our data confirmed the association of different variants at chromosome 20q11 with melanoma risk.

• Authors: Livia Maccioni, P Sivaramakrishna Rachakonda, Dominique Scherer, Justo Lorenzo Bermejo, Dolores Planelles, Celia Requena, Kari Hemminki, Eduardo Nagore, Rajiv Kumar
• Journal: International journal of cancer (Int J Cancer) Vol. 132 Issue 1 Pg. 42-54 (Jan 01 2013) ISSN: 1097-0215 [Electronic] United States
• PMID: 22628150 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 UICC.

Chemical References

• ASIP protein, human
• Agouti Signaling Protein
• NCOA6 protein, human
• Nuclear Receptor Coactivators
• Receptor, Melanocortin, Type 1

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Agouti Signaling Protein (genetics)
• Case-Control Studies
• Child
• Chromosomes, Human, Pair 20
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Male
• Melanoma (genetics)
• Middle Aged
• Nuclear Receptor Coactivators (genetics)
• Odds Ratio
• Polymorphism, Single Nucleotide
• Receptor, Melanocortin, Type 1 (genetics)
• Young Adult