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Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations.
Cancer Epidemiol Biomarkers Prev 2005; 14(9):2208-12CE

Abstract

Major risk factors for melanoma include many nevi, especially dysplastic nevi, fair pigmentation, freckling, poor tanning ability, and germ line mutations in the CDKN2A, CDK4, or MC1R genes. We evaluated the relationship between MC1R and melanoma risk in CDKN2A melanoma-prone families with extensive clinical and epidemiologic data. We studied 395 subjects from 16 American CDKN2A families. Major melanoma risk factors were assessed by clinical examination or questionnaire; MC1R was sequenced. Odds ratios were estimated by unconditional and conditional logistic regression models. We examined the distribution of MC1R variants and median ages at melanoma diagnosis in multiple primary melanoma (MPM) and single primary melanoma (SPM) patients. Presence of multiple MC1R variants was significantly associated with melanoma, even after adjustment for major melanoma risk factors. All 40 MPM patients had at least one MC1R variant; 65% of MPM patients versus only 17% of SPM patients had at least two MC1R variants (P < 0.0001). For all 69 melanoma patients combined, as well as the 40 MPM patients, there was a statistically significant decrease in median age at diagnosis as numbers of MC1R variants increased (P = 0.010 and P = 0.008, respectively). In contrast, no significant reduction in age at melanoma diagnosis was observed for SPM patients (P = 0.91). The current study suggests that the presence of multiple MC1R variants is associated with the development of multiple melanoma tumors in patients with CDKN2A mutations. Additional studies are needed to confirm these findings and to explore the mechanisms that may contribute to this relationship.

Authors+Show Affiliations

Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7236, USA. goldstea@exchange.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16172233

Citation

Goldstein, Alisa M., et al. "Association of MC1R Variants and Risk of Melanoma in Melanoma-prone Families With CDKN2A Mutations." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 14, no. 9, 2005, pp. 2208-12.
Goldstein AM, Landi MT, Tsang S, et al. Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2208-12.
Goldstein, A. M., Landi, M. T., Tsang, S., Fraser, M. C., Munroe, D. J., & Tucker, M. A. (2005). Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 14(9), pp. 2208-12.
Goldstein AM, et al. Association of MC1R Variants and Risk of Melanoma in Melanoma-prone Families With CDKN2A Mutations. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2208-12. PubMed PMID: 16172233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations. AU - Goldstein,Alisa M, AU - Landi,Maria Teresa, AU - Tsang,Shirley, AU - Fraser,Mary C, AU - Munroe,David J, AU - Tucker,Margaret A, PY - 2005/9/21/pubmed PY - 2005/12/13/medline PY - 2005/9/21/entrez SP - 2208 EP - 12 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 14 IS - 9 N2 - Major risk factors for melanoma include many nevi, especially dysplastic nevi, fair pigmentation, freckling, poor tanning ability, and germ line mutations in the CDKN2A, CDK4, or MC1R genes. We evaluated the relationship between MC1R and melanoma risk in CDKN2A melanoma-prone families with extensive clinical and epidemiologic data. We studied 395 subjects from 16 American CDKN2A families. Major melanoma risk factors were assessed by clinical examination or questionnaire; MC1R was sequenced. Odds ratios were estimated by unconditional and conditional logistic regression models. We examined the distribution of MC1R variants and median ages at melanoma diagnosis in multiple primary melanoma (MPM) and single primary melanoma (SPM) patients. Presence of multiple MC1R variants was significantly associated with melanoma, even after adjustment for major melanoma risk factors. All 40 MPM patients had at least one MC1R variant; 65% of MPM patients versus only 17% of SPM patients had at least two MC1R variants (P < 0.0001). For all 69 melanoma patients combined, as well as the 40 MPM patients, there was a statistically significant decrease in median age at diagnosis as numbers of MC1R variants increased (P = 0.010 and P = 0.008, respectively). In contrast, no significant reduction in age at melanoma diagnosis was observed for SPM patients (P = 0.91). The current study suggests that the presence of multiple MC1R variants is associated with the development of multiple melanoma tumors in patients with CDKN2A mutations. Additional studies are needed to confirm these findings and to explore the mechanisms that may contribute to this relationship. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/16172233/Association_of_MC1R_variants_and_risk_of_melanoma_in_melanoma_prone_families_with_CDKN2A_mutations_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16172233 DB - PRIME DP - Unbound Medicine ER -