Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
12753400
TITLE
The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes.
ABSTRACT
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.
DATE PUBLISHED
2003 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2003/05/20 05:00
medline 2004/01/15 05:00
entrez 2003/05/20 05:00
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
INVESTIGATORS
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
MEDLINE JOURNAL
MEDLINETA: Pigment Cell Res
COUNTRY: Denmark
ISSNLINKING: 0893-5785
NLMUNIQUEID: 8800247
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
CA88363 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
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
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Receptor, Melanocortin, Type 1
OTHER ID's