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| PMID |
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| TITLE |
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| The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes. |
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| ABSTRACT |
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| We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2003/05/20 05:00 |
| medline |
2004/01/15 05:00 |
| entrez |
2003/05/20 05:00 |
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| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Sturm RA |
|
Sturm |
Richard A |
RA |
|
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. r.sturm@imb.uq.edu.au |
| Duffy DL |
|
Duffy |
David L |
DL |
|
|
| Box NF |
|
Box |
Neil F |
NF |
|
|
| Chen W |
|
Chen |
Wei |
W |
|
|
| Smit DJ |
|
Smit |
Darren J |
DJ |
|
|
| Brown DL |
|
Brown |
Darren L |
DL |
|
|
| Stow JL |
|
Stow |
Jennifer L |
JL |
|
|
| Leonard JH |
|
Leonard |
J Helen |
JH |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
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| INVESTIGATORS |
|
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| JOURNAL |
|
| VOLUME: 16 |
| ISSUE: 3 |
| TITLE: Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society |
| ISOABBREVIATION: Pigment Cell Res. |
| YEAR: 2003 |
| MONTH: Jun |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Print |
| ISSN: 0893-5785 |
| ISSNTYPE: Print |
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| MEDLINE JOURNAL |
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| MEDLINETA: Pigment Cell Res |
| COUNTRY: Denmark |
| ISSNLINKING: 0893-5785 |
| NLMUNIQUEID: 8800247 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
| Research Support, U.S. Gov't, P.H.S. |
| Review |
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| COMMENTS AND CORRECTIONS |
|
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| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| CA88363 |
NCI NIH HHS |
United States |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Alleles |
|
| Cells, Cultured |
|
| Diseases in Twins |
|
| Eye Color |
genetics |
| Genetic Variation |
genetics |
| Genotype |
genetics |
| Hair Color |
genetics |
| Heterozygote |
genetics |
| Homozygote |
genetics |
| Humans |
genetics |
| Melanocytes |
metabolism |
| Phenotype |
metabolism |
| Polymorphism, Genetic |
metabolism |
| Receptor, Melanocortin, Type 1 |
genetics |
| Risk |
genetics |
| Skin Neoplasms |
genetics |
| Twins, Dizygotic |
genetics |
| Twins, Monozygotic |
genetics |
|
| SUPPLEMENTARY MESH |
|
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| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Receptor, Melanocortin, Type 1 |
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| OTHER ID's |
|
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|
