Home LiteratureArticle Details
PMID: 10631149 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype?

American journal of human genetics ·Vol. 66 ·No. 1 ·2000-01-00 ·Pages 176-86

Palmer JS, Duffy DL, Box NF, Aitken JF, O'Gorman LE, Green AC, Hayward NK, Martin NG, Sturm RA

Abstract

Risk of cutaneous malignant melanoma (CMM) is increased in sun-exposed whites, particularly those with a pale complexion. This study was designed to investigate the relationship of the melanocortin-1 receptor (MC1R) genotype to CMM risk, controlled for pigmentation phenotype. We report the occurrence of five common MC1R variants in an Australian population-based sample of 460 individuals with familial and sporadic CMM and 399 control individuals-and their relationship to such other risk factors as skin, hair, and eye color; freckling; and nevus count. There was a strong relationship between MC1R variants and hair color and skin type. Moreover, MC1R variants were found in 72% of the individuals with CMM, whereas only 56% of the control individuals carried at least one variant (P<.001), a finding independent of strength of family history of melanoma. Three active alleles (Arg151Cys, Arg160Trp, and Asp294His), previously associated with red hair, doubled CMM risk for each additional allele carried (odds ratio 2.0; 95% confidence interval 1. 6-2.6). No such independent association could be demonstrated with the Val60Leu and Asp84Glu variants. Among pale-skinned individuals alone, this association between CMM and MC1R variants was absent, but it persisted among those reporting a medium or olive/dark complexion. We conclude that the effect that MC1R variant alleles have on CMM is partly mediated via determination of pigmentation phenotype and that these alleles may also negate the protection normally afforded by darker skin coloring in some members of this white population.

MeSH Terms
Data Interpretation, Statistical Eye Color/genetics Female Genetic Variation Genotype Hair Color/genetics Humans Linkage Disequilibrium Male Melanoma/genetics Phenotype Pigmentation/genetics Polymerase Chain Reaction Polymorphism, Genetic Receptors, Corticotropin/genetics Receptors, Melanocortin Risk Factors Skin Pigmentation/genetics Whites/genetics
Chemicals
Receptors, Corticotropin Receptors, Melanocortin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Palmer J S
Centre for Molecular and Cellular Biology and Queensland Institute of Medical Research and Joint Genetics Program, University of Queensland, Brisbane, QLD 4072, Australia.
Duffy D L
Box N F
Aitken J F
O'Gorman L E
Green A C
Hayward N K
Martin N G
Sturm R A
References (39)
39 references, click to expand
  1. Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries.
    Proc Natl Acad Sci U S A. 1985 Mar;82(6):1585-8 PMID: 3856838
  2. A simple salting out procedure for extracting DNA from human nucleated cells.
    Nucleic Acids Res. 1988 Feb 11;16(3):1215 PMID: 3344216
  3. Measurement and perception of skin colour in a skin cancer survey.
    Br J Dermatol. 1990 Jul;123(1):77-84 PMID: 2390497
  4. Improved and extended exact and asymptotic methods for the combination of 2 x 2 tables.
    Comput Biomed Res. 1992 Feb;25(1):75-84 PMID: 1547628
  5. Molecular cascades in UV-induced melanogenesis: a central role for melanotropins?
    Pigment Cell Res. 1992 Nov;5(5 Pt 2):348-56 PMID: 1292019
  6. Comparability of surrogate and self-reported information on melanoma risk factors.
    Br J Cancer. 1993 May;67(5):1036-41 PMID: 8494696
  7. Efficient 12-mutation testing in the CFTR gene: a general model for complex mutation analysis.
    Hum Mol Genet. 1993 Feb;2(2):153-8 PMID: 7684636
  8. On the potential role of proopiomelanocortin in skin physiology and pathology.
    Mol Cell Endocrinol. 1993 May;93(1):C1-6 PMID: 8391494
  9. Melanocyte carcinogenesis: facts and fancies.
    Recent Results Cancer Res. 1993;128:59-67 PMID: 8356334
  10. Melanocytic nevi in children. I. Anatomic sites and demographic and host factors.
    Am J Epidemiol. 1994 Feb 15;139(4):390-401 PMID: 8109573
  11. The inherent cytotoxicity of melanin precursors: a revision.
    Biochim Biophys Acta. 1994 Apr 28;1221(3):272-8 PMID: 8167148
  12. Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society.
    J Invest Dermatol. 1994 May;102(5):695-9 PMID: 8176250
  13. Expanding horizons for receptors coupled to G proteins: diversity and disease.
    Curr Opin Cell Biol. 1994 Apr;6(2):191-7 PMID: 8024809
  14. Heterogeneity of melanoma risk in families of melanoma patients.
    Am J Epidemiol. 1994 Dec 1;140(11):961-73 PMID: 7985658
  15. Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. The International Melanoma Analysis Group (IMAGE).
    Int J Cancer. 1995 Aug 9;62(4):367-76 PMID: 7635560
  16. Comparison between familial and nonfamilial melanoma in France.
    Arch Dermatol. 1995 Oct;131(10):1154-9 PMID: 7574832
  17. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.
    Nat Genet. 1995 Nov;11(3):328-30 PMID: 7581459
  18. Mechanisms of ultraviolet light-induced pigmentation.
    Photochem Photobiol. 1996 Jan;63(1):1-10 PMID: 8577860
  19. Naevi and pigmentary characteristics as risk factors for melanoma in a high-risk population: a case-control study in New South Wales, Australia.
    Int J Cancer. 1996 Aug 7;67(4):485-91 PMID: 8759605
  20. The current situation with regard to human melanoma and genetic inferences.
    Curr Opin Oncol. 1996 Mar;8(2):136-42 PMID: 8727306
  21. The Queensland Familial Melanoma Project: study design and characteristics of participants.
    Melanoma Res. 1996 Apr;6(2):155-65 PMID: 8791274
  22. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma.
    Hum Mol Genet. 1996 Oct;5(10):1663-6 PMID: 8894704
  23. Ultraviolet B radiation acts through the nitric oxide and cGMP signal transduction pathway to stimulate melanogenesis in human melanocytes.
    J Biol Chem. 1996 Nov 8;271(45):28052-6 PMID: 8910416
  24. Melanin: a two edged sword?
    Pigment Cell Res. 1997 Jun;10(3):158-61 PMID: 9266603
  25. Ultraviolet light exposure, pigmentary traits and the development of melanocytic naevi and cutaneous melanoma. A case-control study of the German Central Malignant Melanoma Registry.
    Acta Derm Venereol. 1997 Sep;77(5):374-8 PMID: 9298131
  26. Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair.
    Hum Mol Genet. 1997 Oct;6(11):1891-7 PMID: 9302268
  27. Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men.
    Psychol Med. 1997 Nov;27(6):1381-96 PMID: 9403910
  28. Phaeomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: a pilot study.
    Melanoma Res. 1998 Feb;8(1):53-8 PMID: 9508377
  29. Melanocortin 1 receptor variants in an Irish population.
    J Invest Dermatol. 1998 Jul;111(1):119-22 PMID: 9665397
  30. Susceptibility to melanoma: influence of skin type and polymorphism in the melanocyte stimulating hormone receptor gene.
    J Invest Dermatol. 1998 Aug;111(2):218-21 PMID: 9699720
  31. Iris color, skin sun sensitivity, and age-related maculopathy. The Blue Mountains Eye Study.
    Ophthalmology. 1998 Aug;105(8):1359-63 PMID: 9709743
  32. p53 expression and risk factors for cutaneous melanoma: a case-control study.
    Int J Cancer. 1998 Sep 11;77(6):843-8 PMID: 9714052
  33. Human pigmentation genetics: the difference is only skin deep.
    Bioessays. 1998 Sep;20(9):712-21 PMID: 9819560
  34. Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins.
    Genet Epidemiol. 1999;16(1):40-53 PMID: 9915566
  35. Human pigmentation genes and their response to solar UV radiation.
    Mutat Res. 1998 Nov 9;422(1):69-76 PMID: 9920429
  36. CDKN2A variants in a population-based sample of Queensland families with melanoma.
    J Natl Cancer Inst. 1999 Mar 3;91(5):446-52 PMID: 10070944
  37. Skin type, melanoma, and melanocortin 1 receptor variants.
    J Invest Dermatol. 1999 Apr;112(4):512-3 PMID: 10201538
  38. A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs.
    Am J Hum Genet. 1999 Aug;65(2):483-92 PMID: 10417291
  39. Melanocytic naevi and melanoma: an epidemiological perspective.
    Br J Dermatol. 1987 Aug;117(2):137-46 PMID: 3307891
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302711
Published
2000-01-00
Pages
176-86
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1288324
Subset
IM
External Links
PubMed source DOI: 10.1086/302711 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2