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).
Finally, we observed that the expression signatures indentified in phenotypically normal cells carrying CDKN2A mutations or MC1R variants are maintained in skin cancer tumors (melanoma and squamous cell carcinoma).
Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC.
The large number of MC1R alleles and their low frequency, make assessment of the importance of this gene in the pathogenesis of skin cancers difficult.
We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics.
Further research is necessary, especially involving analysis of interactions between variation in MC1R and other genes, to find out if analysis of MC1R polymorphisms could be of any importance for skin cancer prevention.
Our study provides evidence for the contribution of pigmentation genetic variants, in addition to the MC1R variants, to variation in human pigmentary phenotypes and possibly the development of skin cancer.
Natural variation in the coding region of the melanocortin-1 receptor (MC1R) gene is associated with constitutive pigmentation phenotypes and development of melanoma and nonmelanoma skin cancers.
Our findings suggest that in the majority of CDKN2A wt melanoma families, a segregation of variants in low-risk melanoma genes such as MC1R causes increased skin cancer susceptibility, rather than mutations in high-risk cancer predisposing genes, such mutations are more probable to be found in melanoma families with young melanoma cases.
The same group of cases and controls was large enough to show an association between melanocortin 1 receptor gene polymorphism and skin cancer and to reasonably exclude an association between p53 codon 72 polymorphism and skin cancer.
DNA was extracted from salivary samples, and next-generation sequencing (NGS) was conducted using a panel covering all 8 known XP genes (classical XP (XP-A to XP-G) and XP variant) and a skin cancer modifier gene, the melanocortin 1 receptor gene (MC1R).
In a case-control study nested within the Nurses' Health Study, we utilized hierarchical modeling approaches, incorporating quantitative information from these functional studies, to examine the association between particular MC1R alleles and the risk of skin cancers.
Therefore, treatment of contact allergies or skin cancer with alpha-melanocyte-stimulating hormone or other more stable agonists of melanocortin-1 receptor might ameliorate disease or improve antitumoral immune responses.
Inheritance of various MC1R alleles has been associated with a red hair/fair skin phenotype, increased incidence of skin cancer and altered sensitivity to ultraviolet (UV) radiation.
Despite a large number of murine coat-color mutations, only one gene in humans, the melanocortin 1 receptor (MC1R), is known to account for substantial variation in skin and hair color and in skin cancer incidence.
We studied the desensitization and internalization of three variant MC1R forms associated with red hair and increased skin cancer risk: R151C, R160W, and D294H.
Future development of compounds to correct defective MC1R responses secondary to MC1R variants could result in photoprotective benefits for fair-skinned individuals and reduce their skin cancer risk.