title: Germline variation of the melanocortin-1 receptor does not explain shared risk for melanoma and thyroid cancer.
abstract: 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.
  
  
  CONCLUSIONS
  Our data indicate that the strong association between BRAF mutations and MC1R variants previously found in melanoma does not extend to thyroid cancer.
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauer
authors.forename: Julie
authors.initials: J
authors.lastname: Weng
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: Vitor
authors.initials: V
authors.lastname: Trovisco
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics*; D002478:Cells, Cultured / Q000378:metabolism; D015331:Cohort Studies; D004847:Epithelial Cells / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011174:Portugal / Q000453:epidemiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000502:physiology; D012306:Risk; D012495:San Francisco / Q000453:epidemiology; D013030:Spain / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf