Inherited variation at MC1R and ASIP and association with melanoma‐specific survival. Issue 11 (26th November 2014)

• Record Type: Journal Article
• Authors: Taylor, Nicholas J.; Reiner, Anne S.; Begg, Colin B.; Cust, Anne E.; Busam, Klaus J.; Anton‐Culver, Hoda; Dwyer, Terence; From, Lynn; Gallagher, Richard P.; Gruber, Stephen B.; Rosso, Stefano; White, Kirsten A.; Zanetti, Roberto; Orlow, Irene; Thomas, Nancy E.; Rebbeck, Timothy R.; Berwick, Marianne; Kanetsky, Peter A.; on behalf of the GEM Study Group
• Is Part Of: International journal of cancer. Volume 136:Issue 11(2015:Jun. 01)
• Page Start: 2659
• Page End: 2667
• Publication Date: 2014-11-26
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29317
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Melanocortin‐1 receptor (<italic>MC1R</italic>) is a marker of melanoma risk in populations of European ancestry. However, <italic>MC1R</italic> effects on survival are much less studied. We investigated associations between variation at <italic>MC1R</italic> and survival in an international, population‐based series of single primary melanoma patients enrolled into the Genes, Environment, and Melanoma study. <italic>MC1R</italic> genotype data was available for 2, 200 participants with a first incident primary melanoma diagnosis. We estimated the association of <italic>MC1R</italic> genotypes with melanoma‐specific survival (<italic>i.e</italic>., death caused by melanoma) and overall survival using COX proportional hazards modeling, adjusting for established prognostic factors for melanoma. We also conducted stratified analyses by Breslow thickness, tumor site, phenotypic index, and age. In addition, we evaluated haplotypes involving polymorphisms near the Agouti signaling protein gene (<italic>ASIP</italic>) locus for their impacts on survival. Melanoma‐specific survival was inversely associated with carriage of <italic>MC1R</italic> variants in the absence of consensus alleles compared to carriage of at least one consensus allele (hazard ratio (HR) = 0.60; 95% confidence interval (CI): 0.40, 0.90). <italic>MC1R</italic> results for overall survival were consistent with no association. We did not observe any statistical evidence of heterogeneity of effect estimates in stratified analyses. We observed increased hazard of melanoma‐specific death among carriers of the risk haplotype <italic>TG</italic> near the <italic>ASIP</italic> locus (HR = 1.37; 95% CI: 0.91, 2.04) when compared to carriers of the most common <italic>GG</italic> haplotype. Similar results were noted for overall survival. Upon examining the <italic>ASIP TG</italic>/<italic>TG</italic> diplotype, we observed considerably increased hazard of melanoma‐specific death (HR = 5.11; 95% CI: 1.88, 13.88) compared to carriers of the most common <italic>GG</italic>/<italic>GG</italic> diplotype. Our data suggest improved melanoma‐specific survival among carriers of two inherited <italic>MC1R</italic> variants.</p> </abstract>