Document Detail


Germline variation of the melanocortin-1 receptor does not explain shared risk for melanoma and thyroid cancer.
MedLine Citation:
PMID:  19493000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Recently, germline variants of the melanocortin-1 receptor (MC1R) have been shown to be associated with an increased risk for BRAF mutant but not BRAF wild-type cutaneous melanoma. Similar to melanoma, BRAF mutations are also commonly found in papillary thyroid carcinomas. Furthermore, patients with melanoma have an increased risk for thyroid carcinoma and vice versa.
METHODS: To determine whether MC1R variation also represents a risk factor for BRAF mutant thyroid carcinomas, we sequenced BRAF and MC1R in two separate case-control cohorts.
RESULTS: We demonstrate that MC1R is expressed in normal and neoplastic thyroid epithelial cells, albeit at lower levels than in melanocytes. In the first cohort of 66 follicular and 62 papillary thyroid carcinomas (PTC), and 128 matched controls from the San Francisco Bay Area we found no association between the number of MC1R variant alleles and thyroid cancer. Patients with BRAF-mutated tumors had a higher frequency of MC1R variant alleles than their matched controls (P = 0.039). However, contrary to the findings in melanoma, the odds ratio for having a BRAF mutant cancer decreased from 3.9 for carriers of one MC1R allele to 1.5 for carriers of two or more alleles. As the frequency of MC1R alleles varies highly among different ethnic populations, we analysed a second, ethnically more homogeneous cohort from Spain and Portugal, and found no association with PTC nor with BRAF-mutated PTC.
CONCLUSION: Our data indicate that the strong association between BRAF mutations and MC1R variants previously found in melanoma does not extend to thyroid cancer.
Authors:
Jürgen Bauer; Julie Weng; Electron Kebebew; Paula Soares; Vitor Trovisco; Boris C Bastian
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental dermatology     Volume:  18     ISSN:  1600-0625     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-04     Completed Date:  2009-08-25     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  548-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma, Follicular / epidemiology,  genetics*
Adolescent
Adult
Aged
Aged, 80 and over
Carcinoma, Papillary / epidemiology,  genetics*
Cells, Cultured / metabolism
Cohort Studies
Epithelial Cells / metabolism
Ethnic Groups / genetics
Female
Gene Expression Profiling
Genetic Predisposition to Disease
Germ-Line Mutation*
Hair Color / genetics
Humans
Male
Melanocytes / metabolism
Melanoma / epidemiology,  genetics*
Middle Aged
Polymorphism, Single Nucleotide*
Portugal / epidemiology
Proto-Oncogene Proteins B-raf / genetics*
RNA, Messenger / biosynthesis,  genetics
Receptor, Melanocortin, Type 1 / genetics*,  physiology
Risk
San Francisco / epidemiology
Spain / epidemiology
Thyroid Neoplasms / epidemiology,  genetics*
Young Adult
Grant Support
ID/Acronym/Agency:
P01 CA025874/CA/NCI NIH HHS; P01 CA025874-25A10020/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptor, Melanocortin, Type 1; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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