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.
The association of MC1R variant alleles with skin cancer risk remains after correction for pigmentation phenotype, indicating regulation of nonpigmentary pathways.
Several MC1R alleles are associated with red hair, fair skin, increased sensitivity to ultraviolet radiation (the RHC phenotype) and increased skin cancer risk.
We assessed the association of the p53 codon 72 polymorphism with tanning response, and its interaction with MC1R variants on tanning response and skin cancer risk.
MC1R gene sequencing identified in two NBCCS patients affected by multiple basal cell carcinomas a functional MC1R variant, D294H, previously shown to be associated with skin cancer risk.
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.
We studied the desensitization and internalization of three variant MC1R forms associated with red hair and increased skin cancer risk: R151C, R160W, and D294H.
Exploring differences in allele frequencies of MC1R variants across populations with varying pigmentation and differing skin cancer risk may improve our understanding of the complex relationship between MC1R, pigmentation, and carcinogenesis.
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.
The MC1R variants, especially the 151Cys variant, were associated with increased risks of the 3 types of skin cancer, after controlling for hair color, skin color and other skin cancer risk factors.
The melanocortin 1 receptor, a G protein-coupled receptor positively coupled to adenylyl cyclase, is a key regulator of epidermal melanocyte proliferation and differentiation and a determinant of human skin phototype and skin cancer risk.
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.
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.
We conclude that loss-of-function mutations in the MC1R gene sensitize human melanocytes to the DNA damaging effects of UV radiation, which may increase skin cancer risk.