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MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations.
Am J Hum Genet 2001; 69(4):765-73AJ

Abstract

Mutations in the exons of the cyclin-dependent kinase inhibitor gene CDKN2A are melanoma-predisposition alleles which have high penetrance, although they have low population frequencies. In contrast, variants of the melanocortin-1 receptor gene, MC1R, confer much lower melanoma risk but are common in European populations. Fifteen Australian CDKN2A mutation-carrying melanoma pedigrees were assessed for MC1R genotype, to test for possible modifier effects on melanoma risk. A CDKN2A mutation in the presence of a homozygous consensus MC1R genotype had a raw penetrance of 50%, with a mean age at onset of 58.1 years. When an MC1R variant allele was also present, the raw penetrance of the CDKN2A mutation increased to 84%, with a mean age at onset of 37.8 years (P=.01). The presence of a CDKN2A mutation gave a hazard ratio of 13.35, and the hazard ratio of 3.72 for MC1R variant alleles was also significant. The impact of MC1R variants on risk of melanoma was mediated largely through the action of three common alleles, Arg151Cys, Arg160Trp, and Asp294His, that have previously been associated with red hair, fair skin, and skin sensitivity to ultraviolet light.

Authors+Show Affiliations

Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4029, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11500805

Citation

Box, N F., et al. "MC1R Genotype Modifies Risk of Melanoma in Families Segregating CDKN2A Mutations." American Journal of Human Genetics, vol. 69, no. 4, 2001, pp. 765-73.
Box NF, Duffy DL, Chen W, et al. MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. Am J Hum Genet. 2001;69(4):765-73.
Box, N. F., Duffy, D. L., Chen, W., Stark, M., Martin, N. G., Sturm, R. A., & Hayward, N. K. (2001). MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. American Journal of Human Genetics, 69(4), pp. 765-73.
Box NF, et al. MC1R Genotype Modifies Risk of Melanoma in Families Segregating CDKN2A Mutations. Am J Hum Genet. 2001;69(4):765-73. PubMed PMID: 11500805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. AU - Box,N F, AU - Duffy,D L, AU - Chen,W, AU - Stark,M, AU - Martin,N G, AU - Sturm,R A, AU - Hayward,N K, Y1 - 2001/08/08/ PY - 2001/02/26/received PY - 2001/07/19/accepted PY - 2001/8/14/pubmed PY - 2001/10/19/medline PY - 2001/8/14/entrez SP - 765 EP - 73 JF - American journal of human genetics JO - Am. J. Hum. Genet. VL - 69 IS - 4 N2 - Mutations in the exons of the cyclin-dependent kinase inhibitor gene CDKN2A are melanoma-predisposition alleles which have high penetrance, although they have low population frequencies. In contrast, variants of the melanocortin-1 receptor gene, MC1R, confer much lower melanoma risk but are common in European populations. Fifteen Australian CDKN2A mutation-carrying melanoma pedigrees were assessed for MC1R genotype, to test for possible modifier effects on melanoma risk. A CDKN2A mutation in the presence of a homozygous consensus MC1R genotype had a raw penetrance of 50%, with a mean age at onset of 58.1 years. When an MC1R variant allele was also present, the raw penetrance of the CDKN2A mutation increased to 84%, with a mean age at onset of 37.8 years (P=.01). The presence of a CDKN2A mutation gave a hazard ratio of 13.35, and the hazard ratio of 3.72 for MC1R variant alleles was also significant. The impact of MC1R variants on risk of melanoma was mediated largely through the action of three common alleles, Arg151Cys, Arg160Trp, and Asp294His, that have previously been associated with red hair, fair skin, and skin sensitivity to ultraviolet light. SN - 0002-9297 UR - https://www.unboundmedicine.com/medline/citation/11500805/MC1R_genotype_modifies_risk_of_melanoma_in_families_segregating_CDKN2A_mutations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)61132-X DB - PRIME DP - Unbound Medicine ER -