Along with two known pigmentation loci, MC1R and OCA2, the IRF4 rs12203592 T allele was associated with an increased risk of each type of skin cancer (P value, 6.6 × 10(-4) for melanoma, 7.0 × 10(-7) for SCC, and 0.04 for BCC).
Although a 3-arm DOTA construct, which has three carboxylic acids, h has been applied for conjugation to many peptides, we investigated if a 4-arm DOTA construct conjugated to peptides improves chemical properties for melanoma imaging of the melanocortin 1 receptor compared to 3-arm DOTA-conjugated peptides.
Although associated genes have been identified for predisposing people to melanoma risk: HERC2 at 15q13.1, MC1R at 16q24.3 and CDKN2A at 9p21.3, no gene-gene interaction study has been fully explored for melanoma.
Altogether, the factors modifying significantly the melanoma risk associated with CDKN2A mutations (stepwise procedure) were: MC1R and dysplastic nevi (increasing the risk) and GSTT1 (decreasing the risk).
An allele-dose dependent increase in melanoma risk for carriers of variant MC1R alleles (after adjusting for phenotype), with an elevated risk among familial CMM patients, was observed.
As MC1R has already been suggested to affect melanogenesis and increase risk of developing melanoma, it constitutes one of the best models to understand how natural selection acts on pigmentation.
Associations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported.
At similar MC1 receptor numbers per cell, alphaMSH increased intracellular cAMP in wild type MC1R transfected melanoma cells, but the cAMP response was compromised in the variant MC1R transfected clones.
Both B16/F10 and M21 melanoma lesions could be easily imaged by positron emission tomography using <sup>68</sup>Ga-DOTA-GGNle-CycMSH<sub>hex</sub> The first-in-human images of melanoma brain metastases in patients demonstrated the clinical relevance of MC1R as a molecular target for melanoma imaging, highlighting the potential of <sup>68</sup>Ga-DOTA-GGNle-CycMSH<sub>hex</sub> as an MC1R-targeting melanoma imaging probe and underscoring the need to develop MC1R-targeting therapeutic agents for treating patients with metastatic melanoma.
CDKN2A mutation carriers with MC1R variants had a statistically significant lower median age at melanoma diagnosis than CDKN2A mutation carriers with no MC1R variants (37years versus 47years, p-value<0.0001).
Coinheritance of germline mutation in cyclin-dependent kinase inhibitor 2A (CDKN2A) and loss-of-function (LOF) melanocortin 1 receptor (MC1R) variants is clinically associated with exaggerated risk for melanoma.
Considering that melanocortin 1 receptor is crucial for melanocyte proliferation, regulation and differentiation do the naevi of these darker-skinned individuals have specific features that help identify them as carrying one of these melanocortin 1 receptor variants and do melanomas that develop in dark-skinned melanocortin 1 receptor variant carriers have particular characteristics?
Cytochrome P450 CYP2D6 genotypes: association with hair colour, Breslow thickness and melanocyte stimulating hormone receptor alleles in patients with malignant melanoma.
D variants were strongly associated with melanoma (OR = 2.38 [1.38-4.15]) and clustered in the same MC1R domains as R alleles (intracellular 2, transmembrane 2 and 7).
Data from a case-control and a family study from north-eastern Italy on melanoma and a low-risk melanoma-susceptibility gene, MC1R, are used to illustrate the approaches.