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MC1R Variants (mc1r + variants)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Red hair, fair skin and melanoma , melanocortin 1 receptor

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
J. L. Rees
We have previously shown that the MC1R is a key determinant of pigmentary phenotype in man. A range of common and uncommon alleles show diminished function leading to a change in the relative amounts of eumelanin and pheomelanin. As expected, these particular allelic variants are associated with both non-melanoma and melanoma skin cancer and other pigmentary phenotypic characteristics such as freckling. We have recently shown that even against very different genetic backgrounds, the MC1R variants show a phenotypic effect [J Invest Dermatol 2003: 121 (1): 207]. We will present data to explain how the human pigmentary phenotypes can be quantified more appropriately, in terms of both hair melanins and cutaneous response to ultraviolet radiation (submitted and in press). Our results, we would argue, are relevant to those interested in melanocortin signalling in skin and to studies of the genetics of human skin colour and evolution of skin colour. [source]

Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2009
Hongmei Nan
Abstract Human pigmentation is a polygenic quantitative trait with high heritability. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. We evaluated the associations between 15 SNPs in 8 candidate pigmentation genes (TYR, TYRP1, OCA2, SLC24A5, SLC45A2, POMC, ASIP and ATRN) and both pigmentary phenotypes (hair color, skin color and tanning ability) and skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 870 common controls. We found that the TYR Arg402Gln variant was significantly associated with skin color (p -value = 7.7 × 10,4) and tanning ability (p -value = 7.3 × 10,4); the SLC45A2 Phe374Leu variant was significantly associated with hair color (black to blonde) (p -value = 2.4 × 10,7), skin color (p -value = 1.1 × 10,7) and tanning ability (p -value = 2.5 × 10,4). These associations remained significant after controlling for MC1R variants. No significant associations were found between these polymorphisms and the risk of skin cancer. We observed that the TYRP1 rs1408799 and SLC45A2 1721 C>G were associated with melanoma risk (OR, 0.77; 95% CI, 0.60,0.98 and OR, 0.75; 95% CI, 0.60,0.95, respectively). The TYR Ser192Tyr was associated with SCC risk (OR, 1.23; 95% CI, 1.00,1.50). The TYR haplotype carrying only the Arg402Gln variant allele was significantly associated with SCC risk (OR, 1.35; 95% CI, 1.04,1.74). The OCA2 Arg419Gln and ASIP g.8818 A>G were associated with BCC risk (OR, 1.50; 95% CI, 1.06,2.13 and OR, 0.73; 95% CI, 0.53,1.00, respectively). The haplotype near ASIP (rs4911414[T] and rs1015362[G]) was significantly associated with fair skin color (OR, 2.28; 95% CI, 1.46,3.57) as well as the risks of melanoma (OR, 1.68; 95% CI, 1.18,2.39) and SCC (OR, 1.54; 95% CI, 1.08,2.19). These associations remained similar after adjusting for pigmentary phenotypes and MC1R variants. The statistical power of our study was modest and additional studies are warranted to confirm the associations observed in the present study. 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. © 2009 UICC [source]

MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk

INTERNATIONAL JOURNAL OF CANCER, Issue 11 2006
Tadeusz D, bniak
Abstract We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T. © 2006 Wiley-Liss, Inc. [source]

CDKN2A mutations in melanoma families from Uruguay

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2009
A.L. Borges
Summary Background, Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35,70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4, and the minor susceptibility gene MC1R. Objectives, To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay. Methods, We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction,single strand conformational polymorphism analysis. The MC1R gene was sequenced. Results, Mutations in CDKN2A were detected in five of six families: c.,34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families. Conclusions, The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range. [source]