Interactive effects of MC1R and OCA2 on melanoma risk phenotypes

Duffy, D. L.

doi:10.1093/hmg/ddh043

Cited by 257melanin and skin pigmentationGenetic Associations and EpidemiologyCutaneous Melanoma Detection and Management

Interactive effects of MC1R and OCA2 on melanoma risk phenotypes

Duffy, D. L.·2003·Human Molecular Genetics

DOI 10.1093/hmg/ddh043

Open this paper in CoChat — free account

Abstract

The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described.

Integrity signals

Registry

Crossref · 10.1093/hmg/ddh043

Cites

91 of 91 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

An effect of eye color on phenotypes associated with MC1R variant alleles has been reported.
“In this manner, an effect of eye color on phenotypes associated with MC1R variant alleles has been reported (Duffy et al., 2004)”
From Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci (2009) · cites this paper as Duffy et al., 2004

Gentleman R: R: A language for data analysis and graphics
Ihaka, R., & Gentleman, R. (1996) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.1996.10474713 · Cited by 11,747 · see citing works
Longitudinal Data Analysis for Discrete and Continuous Outcomes
Zeger, S. L., & Liang, K. (1986) · Biometrics · doi:10.2307/2531248 · Cited by 7,730 · see citing works
Locally Weighted Regression: An Approach to Regression Analysis by Local Fitting
Cleveland, W. S., & Devlin, S. J. (1988) · Journal of the American Statistical Association · doi:10.1080/01621459.1988.10478639 · Cited by 5,740 · see citing works
Variants of the melanocyte−stimulating hormone receptor gene are associated with red hair and fair skin in humans
Valverde, P., Healy, E., Jackson, I., Rees, J. L., & Thody, A. J. (1995) · Nature Genetics · doi:10.1038/ng1195-328 · Cited by 999 · see citing works
A study of tumor progression: The precursor lesions of superficial spreading and nodular melanoma
Clark, W. H., Elder, D. E., Guerry, D., Epstein, M. N., Greene, M. H., & Horn, M. V. (1984) · Human Pathology · doi:10.1016/s0046-8177(84)80310-x · Cited by 977 · see citing works
Molecular Mechanisms Regulating Hair Follicle Development
Millar, S. E. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01670.x · Cited by 967 · see citing works
Dominant role of the niche in melanocyte stem-cell fate determination
Nishimura, E. K., Jordan, S. A., Oshima, H., Yoshida, H., Osawa, M., Moriyama, M., Jackson, I. J., Barrandon, Y., Miyachi, Y., & Nishikawa, S. (2002) · Nature · doi:10.1038/416854a · Cited by 900 · see citing works
Cyclic AMP a Key Messenger in the Regulation of Skin Pigmentation
Buscà, R., & Ballotti, R. (2000) · Pigment Cell Research · doi:10.1034/j.1600-0749.2000.130203.x · Cited by 809 · see citing works
Microphthalmia Gene Product as a Signal Transducer in cAMP-Induced Differentiation of Melanocytes
Bertolotto, C., Abbe, P., Hemesath, T. J., Bille, K., Fisher, D. E., Ortonne, J. P., & Ballotti, R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.3.827 · Cited by 511 · see citing works
Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype?
Palmer, J. S., 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. (2000) · The American Journal of Human Genetics · doi:10.1086/302711 · Cited by 503 · see citing works
Self-citation
High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Buetow, K. H., Edmonson, M. N., MacDonald, R., Clifford, R., Yip, P., Kelley, J. M., Little, D. P., Strausberg, R. L., KOESTER, H., Cantor, C. R., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.581 · Cited by 459 · see citing works
Melanocortin 1 Receptor (MC1R) Gene Variants are Associated with an Increased Risk for Cutaneous Melanoma Which is Largely Independent of Skin Type and Hair Color
Kennedy, C., ter Huurne, J., Berkhout, M., Gruis, N. A., Bastiaens, M. T., Bergman, W., Willemze, R., & Bavinck, J. N. B. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01421.x · Cited by 407 · see citing works
Evidence for Variable Selective Pressures at MC1R
Harding, R. M., Healy, E., Ray, A. J., Ellis, N. S., Flanagan, N., Todd, C., Dixon, C., Sajantila, A., Jackson, I. J., Birch-Machin, M. A., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/302863 · Cited by 389 · see citing works
Human pigmentation genes: identification, structure and consequences of polymorphic variation
Sturm, R. A., Teasdale, R. D., & Box, N. F. (2001) · Gene · doi:10.1016/s0378-1119(01)00694-1 · Cited by 388 · see citing works
The genetics of pigmentation: from fancy genes to complex traits
Barsh, G. S. (1996) · Trends in Genetics · doi:10.1016/0168-9525(96)10031-7 · Cited by 364 · see citing works
The pigmentary system : physiology and pathophysiology
Nordlund, J. J. (1998) · Cited by 357 · see citing works
Characterization of Melanocyte Stimulating Hormone Receptor Variant Alleles in Twins with Red Hair
Box, N. F., Wyeth, J. R., O'Gorman, L. E., Martin, N. G., & Sturm, R. A. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.11.1891 · Cited by 340 · see citing works
Pheomelanin as well as Eumelanin Is Present in Human Epidermis
Thody, A. J., Higgins, E. M., Wakamatsu, K., Ito, S., Burchill, S. A., & Marks, J. M. (1991) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12480680 · Cited by 311 · see citing works
MC1R Genotype Modifies Risk of Melanoma in Families Segregating CDKN2A Mutations
Box, N. F., Duffy, D. L., Chen, W., Stark, M. S., Martin, N. G., Sturm, R. A., & Hayward, N. K. (2001) · The American Journal of Human Genetics · doi:10.1086/323412 · Cited by 309 · see citing works
Self-citation
Broad-Spectrum Sunscreen Use and the Development of New Nevi in White Children
Gallagher, R. P., Rivers, J. K., Lee, T. K., Bajdik, C. D., McLean, D. I., & Coldman, A. J. (2000) · JAMA · doi:10.1001/jama.283.22.2955 · Cited by 294 · see citing works
High Polymorphism at the Human Melanocortin 1 Receptor Locus
Rana, B. K., Hewett‐Emmett, D., Li, J., Chang, B. H.-J., Sambuughin, N., Lin, M., Watkins, W. S., Bamshad, M. J., Jorde, L. B., Ramsay, M., et al. (1999) · Genetics · doi:10.1093/genetics/151.4.1547 · Cited by 286 · see citing works
Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation
Flanagan, N. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.17.2531 · Cited by 279 · see citing works
Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: Systematic overview of 10 case‐control studies
Bliss, J. M., Ford, D., Swerdlow, A. J., Armstrong, B. K., Cristofolini, M., Elwood, J. M., Green, A. C., Holly, E. A., Mack, T. M., MacKie, R. M., et al. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910620402 · Cited by 262 · see citing works
Melanocortin 1 Receptor Variants in an Irish Population
Smith, R., Healy, E., Siddiqui, S., Flanagan, N., Steijlen, P. M., Rosdahl, I. K., Jacques, J. P., Rogers, S., Turner, R., Jackson, I. J., et al. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00252.x · Cited by 249 · see citing works
Melanocortin-1 Receptor Gene Variants Determine the Risk of Nonmelanoma Skin Cancer Independently of Fair Skin and Red Hair
Bastiaens, M. T., ter Huurne, J. A. C., Kielich, C. J., Gruis, N. A., Westendorp, R. G. J., Vermeer, B. J., & Bavinck, J. N. B. (2001) · The American Journal of Human Genetics · doi:10.1086/319500 · Cited by 248 · see citing works
Loss of Function Mutations of the Human Melanocortin 1 Receptor Are Common and Are Associated with Red Hair
Schiöth, H. B., Phillips, S. R., Rudzish, R., Birch‐Machin, M. A., Wikberg, J. E. S., & Rees, J. L. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0935 · Cited by 238 · see citing works
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
Zhu, G., Duffy, D. L., Eldridge, A., Grace, M., Mayne, C., O'Gorman, L. E., Aitken, J. F., Neale, M. C., Hayward, N. K., Green, A. C., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302494 · Cited by 237 · see citing works
Self-citation
The melanocortin-1-receptor gene is the major freckle gene
Bastiaens, M. T. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.16.1701 · Cited by 234 · see citing works
α-Melanocyte-stimulating Hormone Signaling Regulates Expression of microphthalmia, a Gene Deficient in Waardenburg Syndrome
Price, E. R., Horstmann, M. A., Wells, A. G., Weilbaecher, K. N., Takemoto, C. M., Landis, M. W., & Fisher, D. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.33042 · Cited by 225 · see citing works
Skin colour and skin cancer –MC1R, the genetic link
Sturm, R. A. (2002) · Melanoma Research · doi:10.1097/00008390-200209000-00001 · Cited by 224 · see citing works
Sunlight: A major factor associated with the development of melanocytic nevi in Australian schoolchildren
Kelly, J. W., Rivers, J. K., MacLennan, R., Harrison, S. L., Lewis, A., & Tate, B. J. (1994) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(94)70005-2 · Cited by 222 · see citing works
Suntan, sunburn, and pigmentation factors and the frequency of acquired melanocytic nevi in children. Similarities to melanoma: the Vancouver Mole Study
Gallagher, R. P. (1990) · Archives of Dermatology · doi:10.1001/archderm.126.6.770 · Cited by 220 · see citing works
Human TROP-2 is a tumor-associated calcium signal transducer
Rapani, E., Sacchetti, A., Corda, D., & Alberti, S. (1998) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19980529)76:5 · Cited by 215 · see citing works
Organization and sequence of the human P gene and identification of a new family of transport proteins.
Lee, S.-T., Nicholls, R., Jong, M. T. C., Fukai, K., & Spritz, R. (1995) · Genomics · doi:10.1016/0888-7543(95)80220-g · Cited by 210 · see citing works
Humanmelanocortin 1 receptorvariants, receptor function and melanocyte response to UV radiation
Scott, M., Wakamatsu, K., Ito, S., Kadekaro, A. L., Kobayashi, N., Groden, J. L., Kavanagh, R. J., Takakuwa, T., Virador, V. M., Hearing, V. J., et al. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.11.2349 · Cited by 203 · see citing works
Identification and Analysis of Error Types in High-Throughput Genotyping
Ewen, K. R., Bahlo, M., Treloar, S. A., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/303048 · Cited by 198 · see citing works
Melanocortin-1 Receptor Genotype is a Risk Factor for Basal and Squamous Cell Carcinoma
Box, N. F., Chen, W., Sturm, R. A., Duffy, D. L., Irving, R. E., Russell, A., Griffyths, L. R., Parsons, P. G., & Green, A. C. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2001.01224.x · Cited by 182 · see citing works
Self-citation
Modulation of melanogenic protein expression during the switch from eu-to pheomelanogenesis
Kobayashi, T., Vieira, W. D., Potterf, B., Sakai, C., Imokawa, G., & Hearing, V. J. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.6.2301 · Cited by 174 · see citing works
Iris color, skin sun sensitivity, and age-related maculopathy
Mitchell, P., Smith, W. H., & Wang, J. J. (1998) · Ophthalmology · doi:10.1016/s0161-6420(98)98013-7 · Cited by 162 · see citing works
TYRP1 and MC1R genotypes and their effects on coat color in dogs
Schmutz, S. M., Berryere, T. G., & Goldfinch, A. D. (2002) · Mammalian Genome · doi:10.1007/s00335-001-2147-2 · Cited by 162 · see citing works
Influence of α‐melanocyte‐stimulating hormone and of ultraviolet radiation on the transfer of melanosomes to keratinocytes
Virador, V. M., Müller, J., Wu, X., ABDEL‐MALEK, Z. A., Yu, Z., Ferrans, V. J., Kobayashi, N., Wakamatsu, K., Ito, S., Hammer, J. A., et al. (2001) · The FASEB Journal · doi:10.1096/fj.01-0518fje · Cited by 146 · see citing works
Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation.
Tada, A., Suzuki, I., Im, S., Davis, M. B., Cornelius, J. R., Babcock, G. F., Nordlund, J. J., & ABDEL‐MALEK, Z. A. (1998) · PubMed · Cited by 144 · see citing works
Melanocortin-1-receptor gene and sun sensitivity in individuals without red hair
Healy, E., Flannagan, N., Ray, A. J., Todd, C., Jackson, I. J., Matthews, J. N. S., Birch‐Machin, M. A., & Rees, J. L. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02042-0 · Cited by 143 · see citing works
Genetics of Risk Factors for Melanoma: an Adult Twin Study of Nevi and Freckles
Bataille, V. A., Snieder, H., MacGregor, A. J., Sasieni, P. D., & Spector, T. D. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.6.457 · Cited by 142 · see citing works
Activation of the cyclic AMP pathway by alpha-melanotropin mediates the response of human melanocytes to ultraviolet B radiation.
Im, S., Moro, O., Peng, F., Medrano, E. E., Cornelius, J., Babcock, G. F., Nordlund, J. J., & ABDEL‐MALEK, Z. A. (1998) · PubMed · Cited by 141 · see citing works
Functional variation of MC1R alleles from red-haired individuals
Healy, E. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.21.2397 · Cited by 138 · see citing works
Melanocytic Nevi in Children
English, D. R., & Armstrong, B. K. (1994) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a117011 · Cited by 137 · see citing works
A Genome Scan for Eye Color in 502 Twin Families: Most Variation is due to a QTL on Chromosome 15q
Zhu, G., Evans, D. M., Duffy, D. L., Montgomery, G. W., Medland, S. E., Gillespie, N. A., Ewen, K. R., Jewell, M., Liew, Y., Hayward, N. K., et al. (2004) · Twin Research · doi:10.1375/twin.7.2.197 · Cited by 119 · see citing works
Self-citation
Human Pigmentation Phenotype: A Point Mutation Generates Nonfunctional MSH Receptor
Frändberg, P., Doufexis, M., Kapas, S., & Chhajlani, V. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8459 · Cited by 116 · see citing works
Chromatin remodeling: a marriage between two families?
Pollard, K. J., & Peterson, C. L. (1998) · BioEssays · doi:10.1002/(sici)1521-1878(199809)20:9 · Cited by 109 · see citing works
Weight gain with breast cancer adjuvant treatment
Levine, E. G., Raczynski, J. M., & Carpenter, J. T. (1991) · Cancer · doi:10.1002/1097-0142(19910401)67:7 · Cited by 99 · see citing works
Benign pigmented nevi in children. Prevalence and associated factors: the West Midlands, United Kingdom Mole Study
Pope, D. J. (1992) · Archives of Dermatology · doi:10.1001/archderm.128.9.1201 · Cited by 98 · see citing works
MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2)
King, R. A., Willaert, R. K., Schmidt, R. M., Pietsch, J., Savage, S., Brott, M. J., Fryer, J. P., Summers, C. G., & Oetting, W. S. (2003) · The American Journal of Human Genetics · doi:10.1086/377569 · Cited by 98 · see citing works
P gene as an inherited biomarker of human eye color.
Rebbeck, T. R., Kanetsky, P. A., Walker, A. H., Holmes, R., Halpern, A. C., Schuchter, L. M., Elder, D. E., & Guerry, D. (2002) · PubMed · Cited by 96 · see citing works
Molecular Regulation of Melanocyte Senescence
Bennett, D. C., & Medrano, E. E. (2002) · Pigment Cell Research · doi:10.1034/j.1600-0749.2002.02036.x · Cited by 95 · see citing works
Mitogen- and Ultraviolet-B-Induced Signaling Pathways in Normal Human Melanocytes
Tada, A., Pereira, E., Beitner‐Johnson, D., Kavanagh, R. J., & ABDEL‐MALEK, Z. A. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01694.x · Cited by 93 · see citing works
Naevi in schoolchildren in Scotland and Australia
Fritschi, L., McHenry, P. M., Green, A. C., et al. (1994) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1994.tb13106.x · Cited by 90 · see citing works
Human DNA Sequence Variation in a 6.6-kb Region Containing the Melanocortin 1 Receptor Promoter
Makova, K. D., Ramsay, M., Jenkins, T., & Li, W. (2001) · Genetics · doi:10.1093/genetics/158.3.1253 · Cited by 87 · see citing works
Comparative analysis of melanins and melanosomes produced by various coat color mutants
PROTA, G., LAMOREUX, M. L., MULLER, J., KOBAYASHI, T., NAPOLITANO, A., VINCENSI, M. R., SAKAI, C., & HEARING, V. J. (1995) · Pigment Cell Research · doi:10.1111/j.1600-0749.1995.tb00657.x · Cited by 71 · see citing works
Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population
Passmore, L. A., Käsmann‐Kellner, B., & Weber, B. H. F. (1999) · Human Genetics · doi:10.1007/s004390051090 · Cited by 71 · see citing works
Assignment of Genes Coding for Brown Eye Colour (BEY2) and Brown Hair Colour (HCL3) on Chromosome 15q
Eiberg, H., & Mohr, J. (1996) · European Journal of Human Genetics · doi:10.1159/000472205 · Cited by 71 · see citing works
The Epidemiology of Acquired Melanocytic Nevi: A Brief Review
Gallagher, R. P., & McLean, D. I. (1995) · Dermatologic Clinics · doi:10.1016/s0733-8635(18)30065-2 · Cited by 68 · see citing works
Interaction between the melanocortin-1 receptor andP genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population
Akey, J. M., Wang, H., Xiong, M., Wu, H., Liu, W., Shriver, M. D., & Jin, L. (2001) · Human Genetics · doi:10.1007/s004390100524 · Cited by 67 · see citing works
Rac1 Mediates Dendrite Formation in Response to Melanocyte Stimulating Hormone and Ultraviolet Light in a Murine Melanoma Model
Scott, G., & Cassidy, L. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00276.x · Cited by 66 · see citing works
The Pinkeyed‐Dilution Protein and the Eumelanin/Pheomelanin Switch: In Support of a Unifying Hypothesis
Lamoreux, M. L., Zhou, B.-K., Rosemblat, S., & Orlow, S. J. (1995) · Pigment Cell Research · doi:10.1111/j.1600-0749.1995.tb00673.x · Cited by 62 · see citing works
Activation of a cAMP Pathway and Induction of Melanogenesis Correlate with Association of p16INK4 and p27KIP1 to CDKs, Loss of E2F-Binding Activity, and Premature Senescence of Human Melanocytes
Haddad, M. M., Xu, W., Schwahn, D. J., Liao, F., & Medrano, E. E. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4688 · Cited by 62 · see citing works
Melanocyte Distribution in Forearm Epidermis of Freckled Human Subjects1
Breathnach, A. S. (1957) · Journal of Investigative Dermatology · doi:10.1038/jid.1957.98 · Cited by 60 · see citing works
Human acquired naevi are clonal
Robinson, W. A., Lemon, M., Elefanty, A. G., Harrison-Smith, M., Markham, N., & Norris, D. A. (1998) · Melanoma Research · doi:10.1097/00008390-199812000-00004 · Cited by 58 · see citing works
Variation and Covariates of the Number of Benign Nevi in Adolescents
Coombs, B. D., Sharpies, K. J., Cooke, K. R., et al. (1992) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a116499 · Cited by 58 · see citing works
Microanalysis of Melanins in Mammalian Hair by Alkaline Hydrogen Peroxide Degradation: Identification of a New Structural Marker of Pheomelanins
Napolitano, A., Vincensi, M. R., Donato, P. D., Prota, G., & Monfrecola, G. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00977.x · Cited by 56 · see citing works
A twin study of skin reflectance
Clark, P., Stark, A. E., Walsh, R. J., Jardine, R., & Martin, N. G. (1981) · Annals of Human Biology · doi:10.1080/03014468100005371 · Cited by 55 · see citing works
Evolution of Melanocytic Nevi on the Faces and Necks of Adolescents: A 4 y Longitudinal Study
Siskind, V., Darlington, S., Green, L., et al. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01685.x · Cited by 54 · see citing works
Redefining the Skin's Pigmentary System with a Novel Tyrosinase Assay
Han, R. X., Baden, H. P., Brissette, J. L., et al. (2002) · Pigment Cell Research · doi:10.1034/j.1600-0749.2002.02027.x · Cited by 53 · see citing works
Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa
Kerr, R. A., Stevens, G., Manga, P., Salm, S. N., John, P. R., Haw, T., & Ramsay, M. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200002)15:2 · Cited by 50 · see citing works
Ephelides are More Related to Pigmentary Constitutional Host Factors than Solar Lentigines
Bastiaens, M. T., Westendorp, R. G. J., Vermeer, B. J., & Bavinck, J. N. B. (1999) · Pigment Cell Research · doi:10.1111/j.1600-0749.1999.tb00765.x · Cited by 48 · see citing works
The incidence of melanocytic naevi in adolescent children in Queensland, Australia
Green, A., Siskind, V., & GREEN, L. (1995) · Melanoma Research · doi:10.1097/00008390-199506000-00003 · Cited by 46 · see citing works
The underwhite (uw) locus acts autonomously and reduces the production of melanin
Lehman, A. L., Silvers, W. K., Puri, N., Wakamatsu, K., Ito, S., & Brilliant, M. H. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00107.x · Cited by 42 · see citing works
An oncornavirus isolated from human cancer cell line
Ilyin, K. V., Bykovsky, A. F., & Zhdanov, V. M. (1973) · Cancer · doi:10.1002/1097-0142(197307)32:1 · Cited by 42 · see citing works
The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution
Smith, A. G., Box, N. F., Marks, L. H., Chen, W., Smit, D. J., Wyeth, J. R., Huttley, G. A., Easteal, S., & Sturm, R. A. (2001) · Gene · doi:10.1016/s0378-1119(01)00791-0 · Cited by 42 · see citing works
The Relation Between Melanocortin 1 Receptor Genotype and Experimentally Assessed Ultraviolet Radiation Sensitivity
Flanagan, N., Ray, A. J., Todd, C., Birch‐Machin, M. A., & Rees, J. L. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01532.x · Cited by 33 · see citing works
HAIR‐COLOUR VARIATION IN THE UNITED KINGDOM*
SUNDERLAND, B. E. (1956) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1955.tb01286.x · Cited by 31 · see citing works
Comparability of naevus counts between and within examiners, and comparison with computer image analysis
Aitken, J. F., Green, A. C., Eldridge, A., et al. (1994) · British Journal of Cancer · doi:10.1038/bjc.1994.88 · Cited by 26 · see citing works
Estimation of genetic model parameters: Variables correlated with a quantitative phenotype exhibiting major locus inheritance
Hasstedt, S. J., Moll, P. P., & Rao, D. C. (1989) · Genetic Epidemiology · doi:10.1002/gepi.1370060203 · Cited by 25 · see citing works
Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online.
Oetting, W. S., Gardner, J. M., Fryer, J. P., Ching, A., Durham‐Pierre, D., King, R. A., & Brilliant, M. H. (1998) · PubMed · doi:10.1002/(sici)1098-1004(1998)12:6 · Cited by 23 · see citing works
Alpha-melanocyte stimulating hormone potentiates p16/CDKN2A expression in human skin after ultraviolet irradiation.
Pavey, S. J., & Gabrielli, B. G. (2002) · PubMed · Cited by 23 · see citing works
Spontaneous de-differentiation correlates with extended lifespan in transformed thyroid epithelial cells: An epigenetic mechanism of tumour progression?
BOND, J. A., Ness, G. O., Rowson, J., Ivan, M., White, D., & Wynford‐Thomas, D. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960807)67:4 · Cited by 21 · see citing works
Melanin density and melanin type predict melanocytic naevi in 19–20 year olds of northern European ancestry
Dwyer, T., Prota, G., Blizzard, L., et al. (2000) · Melanoma Research · doi:10.1097/00008390-200008000-00011 · Cited by 20 · see citing works
Phenotypic assortative mating in segregation analysis
Hasstedt, S. J. (1995) · Genetic Epidemiology · doi:10.1002/gepi.1370120202 · Cited by 19 · see citing works
Impact of demographic distribution and population growth rate on haplotypic diversity linked to a disease gene and their consequences for the estimation of recombination rate: Example of a French Canadian population
Austerlitz, F., & Heyer, É. (1999) · Genetic Epidemiology · doi:10.1002/(sici)1098-2272(1999)16:1 · Cited by 11 · see citing works
Hair colour in the Faroe and Orkney Islands
Suter, D. (1979) · Annals of Human Biology · doi:10.1080/03014467900003401 · Cited by 5 · see citing works
A skin clinic at Long Bay Jail.
MacLennan, R., Kelly, J. W., & Martin, N. G. (1999) · PubMed · Cited by 2 · see citing works

Flagged first, then by citations

Sorted by citations

A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation
Han, J., Kraft, P., Nan, H., Guo, Q., Chen, C., Qureshi, A., Hankinson, S. E., Hu, F. B., Duffy, D. L., Zhao, Z. Z., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000074 · Cited by 499 · see citing works
Self-citation
Molecular genetics of human pigmentation diversity
Sturm, R. A. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp003 · Cited by 379 · see citing works
A Single SNP in an Evolutionary Conserved Region within Intron 86 of the HERC2 Gene Determines Human Blue-Brown Eye Color
Sturm, R. A., Duffy, D. L., Zhao, Z. Z., Leite, F. P. N., Stark, M. S., Hayward, N. K., Martin, N. G., & Montgomery, G. W. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.11.005 · Cited by 378 · see citing works
MC1R variants, melanoma and red hair color phenotype: A meta‐analysis
Raimondi, S., Sera, F., Gandini, S., Iodice, S., Caini, S., Maisonneuve, P., & Fargnoli, M. C. (2008) · International Journal of Cancer · doi:10.1002/ijc.23396 · Cited by 349 · see citing works
<i>MC1R</i> Germline Variants Confer Risk for <i>BRAF</i> -Mutant Melanoma
Landi, M. T., Bauer, J., Pfeiffer, R. M., Elder, D. E., Hulley, B., Minghetti, P., Calista, D., Kanetsky, P. A., Pinkel, D., & Bastian, B. C. (2006) · Science · doi:10.1126/science.1127515 · Cited by 346 · see citing works
Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene
Kayser, M., Liu, F., Janssens, A. C. J. W., Rivadeneira, F., Lao, O., van Duijn, K., Vermeulen, M., Arp, P., Jhamai, M. M., van IJcken, W. F. J., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.10.003 · Cited by 260 · see citing works
α-Melanocortin and Endothelin-1 Activate Antiapoptotic Pathways and Reduce DNA Damage in Human Melanocytes
Kadekaro, A. L., Kavanagh, R., Kanto, H., Terzieva, S., Hauser, J., Kobayashi, N., Schwemberger, S., Cornelius, J., Babcock, G., Shertzer, H. G., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4535 · Cited by 259 · see citing works
A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation
Duffy, D. L., Montgomery, G. W., Chen, W., Zhao, Z. Z., Le, L., James, M. R., Hayward, N. K., Martin, N. G., & Sturm, R. A. (2007) · The American Journal of Human Genetics · doi:10.1086/510885 · Cited by 240 · see citing works
Self-citation
<scp>MC</scp>1R, Eumelanin and Pheomelanin: Their Role in Determining the Susceptibility to Skin Cancer
Nasti, T. H., & Timares, L. (2015) · Photochemistry and Photobiology · doi:10.1111/php.12335 · Cited by 217 · see citing works
Human pigmentation variation: evolution, genetic basis, and implications for public health
Parra, E. J. (2007) · American Journal of Physical Anthropology · doi:10.1002/ajpa.20727 · Cited by 191 · see citing works
<scp>MC</scp>1R, the c<scp>AMP</scp> pathway, and the response to solar <scp>UV</scp>: extending the horizon beyond pigmentation
García‐Borrón, J. C., Abdel‐Malek, Z., & Jiménez‐Cervantes, C. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12257 · Cited by 187 · see citing works
MC1R and the response of melanocytes to ultraviolet radiation
Rouzaud, F., Kadekaro, A. L., Abdel-Malek, Z. A., & Hearing, V. J. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.09.014 · Cited by 173 · see citing works
MC1R Is a Potent Regulator of PTEN after UV Exposure in Melanocytes
Cao, J., Wan, L., Hacker, E., Dai, X., Lenna, S., Jimenez-Cervantes, C., Wang, Y., Leslie, N. R., Xu, G. X., Widlund, H. R., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.010 · Cited by 144 · see citing works
Melanocortin 1 receptor and risk of cutaneous melanoma: A meta‐analysis and estimates of population burden
Williams, P. F., Olsen, C. M., Hayward, N. K., & Whiteman, D. C. (2011) · International Journal of Cancer · doi:10.1002/ijc.25804 · Cited by 143 · see citing works
Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin
Wakamatsu, K., Kavanagh, R., Kadekaro, A. L., Terzieva, S., Sturm, R. A., Leachman, S., Abdel‐Malek, Z., & Ito, S. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2006.00293.x · Cited by 137 · see citing works
Germline MC1R status influences somatic mutation burden in melanoma
Robles-Espinoza, C. D., Roberts, N. D., Chen, S., Leacy, F. P., Alexandrov, L. B., Pornputtapong, N., Halaban, R., Krauthammer, M., Cui, R., Timothy Bishop, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12064 · Cited by 124 · see citing works
Prediction of eye and skin color in diverse populations using seven SNPs
Spichenok, O., Budimlija, Z. M., Mitchell, A. A., Jenny, A., Kovacevic, L., Marjanovic, D., Caragine, T., Prinz, M., & Wurmbach, E. (2011) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2010.10.005 · Cited by 121 · see citing works
Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci
Cook, A. L., Chen, W., Thurber, A. E., Smit, D. J., Smith, A. G., Bladen, T. G., Brown, D. L., Duffy, D. L., Pastorino, L., Bianchi-Scarra, G., et al. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.211 · Cited by 116 · see citing works
Self-citation
Melanocortin 1 receptor variants: Functional role and pigmentary associations
Dessinioti, C., Antoniou, C., Katsambas, A., & Stratigos, A. J. (2011) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2011.00970.x · Cited by 111 · see citing works
Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations
Candille, S. I., Absher, D. M., Beleza, S., Bauchet, M., McEvoy, B., Garrison, N. A., Li, J. Z., Myers, R. M., Barsh, G. S., Tang, H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048294 · Cited by 111 · see citing works
Worldwide polymorphism at the MC1R locus and normal pigmentation variation in humans
Makova, K., & Norton, H. (2005) · Peptides · doi:10.1016/j.peptides.2004.12.032 · Cited by 101 · see citing works
Estimating the attributable fraction for melanoma: A meta-analysis of pigmentary characteristics and freckling
Olsen, C. M., Carroll, H. J., & Whiteman, D. C. (2010) · International Journal of Cancer · doi:10.1002/ijc.25243 · Cited by 89 · see citing works
Melanocortin MC1 receptor in human genetics and model systems
Beaumont, K. A., Wong, S. S., Ainger, S. A., Liu, Y. Y., Patel, M. P., Millhauser, G. L., Smith, J. J., Alewood, P. F., Leonard, J. H., & Sturm, R. A. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.11.040 · Cited by 47 · see citing works
Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism: GSTP1 rs1695 polymorphism associated with melanoma
Ibarrola-Villava, M., Martin-Gonzalez, M., Lazaro, P., Pizarro, A., Lluch, A., & Ribas, G. (2012) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2012.10831.x · Cited by 44 · see citing works
Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: pigmentation marker, ultrastructural and UV-survival studies
Leonard, J. H., Marks, L. H., Chen, W., Cook, A. L., Boyle, G. M., Smit, D. J., Brown, D. L., Stow, J. L., Parsons, P. G., & Sturm, R. A. (2003) · Pigment Cell Research · doi:10.1034/j.1600-0749.2003.00033.x · Cited by 39 · see citing works
‘Mind your Moles’ study: protocol of a prospective cohort study of melanocytic naevi
Koh, U., Janda, M., Aitken, J. F., Duffy, D. L., Menzies, S., Sturm, R. A., Schaider, H., Betz-Stablein, B., Prow, T., Soyer, H. P., et al. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-025857 · Cited by 36 · see citing works
Self-citation

Penetrance of Fra(X) gene: Influence of grandparental origin of the gene, mental status of the carrier mother, and presence of a normal transmitting male
Smits, A. P. T., van Oost, B. A., de Haan, A. F. J., et al. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320430157 · Cited by 8 · see citing works
The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings
McGurk, K. A., Zhang, X., Theotokis, P. I., Thomson, K. L., Harper, A. R., Buchan, R. J., Mazaika, E., Ormondroyd, E., Wright, W. T., Macaya, D., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.08.003 · Cited by 69 · see citing works
The penetrance of rare variants in cardiomyopathy-associated genes: a cross-sectional approach to estimate penetrance for secondary findingsPreprint
McGurk, K. A., Zhang, X., Theotokis, P. I., et al. (2023) · medRxiv · doi:10.1101/2023.03.15.23287112 · Cited by 3 · see citing works
Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory features
Rosanoff, M., & Ottman, R. (2008) · Neurology · doi:10.1212/01.wnl.0000323926.77565.ee · Cited by 69 · see citing works
Risk estimation in autosomal dominant disorders with reduced penetrance.
Emery, A. E. H. (1986) · Journal of Medical Genetics · doi:10.1136/jmg.23.4.316 · Cited by 9 · see citing works

Authors: Duffy, D. L.
Affiliations: QIMR Berghofer Medical Research Institute (AU)
Corresponding author: Duffy, D. L.
ORCID: Duffy, D. L.
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2003-12-17
Volume: 13
Issue: 4
Pages: 447-461
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddh043
OpenAlex: W2127998528
Cited by: 257
References: 91
Citations by year: 2026: 4 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 14 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 5 · 2014: 15 · 2013: 16 · 2012: 16
FWCI: 4.62
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA088363, CA88363)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords: MC1R, OCA2, melanoma risk, red hair, skin reflectance, freckling, nevus count, eye color, gene-gene interaction, melanin pigmentation
MeSH terms: Adolescent, Alleles, Eye Color, Hair Color, Humans, Mutation, Phenotype, Skin Pigmentation, Twins, Genetic Variation, Genetic Predisposition to Disease, Membrane Transport Proteins, Receptor, Melanocortin, Type 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Interactive effects of MC1R and OCA2 on melanoma risk phenotypes

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks