Variants at the 9p21 locus and melanoma risk

Abstract

BackgroundThe influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS).MethodsIn the present study we genotyped, 25 SNPs that tag 273 variants on chromosome 9p21 in 837 melanoma cases and 1154 controls from Spain. Ten SNPs were selected based on previous associations, reported in GWAS, with either melanocytic nevi or melanoma risk or both. The other 15 SNPs were selected to fine map the CDKN2A gene region.ResultsAll the 10 variants selected from the GWAS showed statistically significant association with melanoma risk. Statistically significant association with melanoma risk was also observed for the carriers of the variant T-allele of rs3088440 (540 C>T) at the 3’ UTR of CDKN2A gene with an OR 1.52 (95% CI 1.14-2.04). Interaction analysis between risk associated polymorphisms and previously genotyped MC1R variants, in the present study, did not show any statistically significant association. Statistical significant association was observed for the interaction between phototypes and the rs10811629 (located in intron 5 of MTAP). The strongest association was observed between the homozygous carrier of the A–allele and phototype II with an OR of 15.93 (95% CI 5.34-47.54).ConclusionsOur data confirmed the association of different variants at chromosome 9p21 with melanoma risk and we also found an association of a variant with skin phototypes.

Epigenetic regulation in human melanoma: past and future

“…This polymorphism was also associated by GWAS with breast cancer risk. 90 These results strongly suggest that ANRIL is involved in the etiology of melanoma.…”

“…This variant tagged a total of 6 SNPs, of which 3 were found to be located in the intergenic region and the others in intron 1 of CDKN2A, the 3' UTR of CDKN2B and intron 3 of ANRIL. 90 Further elucidation of ANRIL as regards to its function and the mechanism by which it controls the INK4a-ARF-INK4b locus will help a great deal in understanding its role in melanoma. ANRIL has potential as a therapeutic target, or a diagnostic marker for early detection of melanoma.…”

Skin Pigmentation Genetics for the Clinic

“…About 5-10% of melanoma is associated with familial predisposition with affected first-or second-degree relatives. Of those, 20-40% familial melanoma is linked to chromosome 9p21 locus and a proportion of 9p21-linked families carry diseasesegregating germline mutations in the cyclin-dependent kinase inhibitor 2A CDKN2A gene [91][92][93] . The majority of mutations at this locus are single base pair substitutions in exons 1α and 2, affecting the function of the protein p16/INK4A.…”

Association of common variants in MTAP with susceptibility and overall survival of osteosarcoma: a two-stage population-based study in Han Chinese

“…Loss of MTAP expression can exert a tumor promoting effect, suggesting that MTAP may function as a tumor suppressor gene 21,30,31,38. Moreover, the genetic polymorphism of MTAP was also considered as one of the potential genetic factors in various tumors 29,39-41. However, the exact mechanism by which the MTAP genetic polymorphisms affect the susceptibility of OS remains elusive.…”