Germline variation of the melanocortin-1 receptor does not explain shared risk for melanoma and thyroid cancer.
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.
Bauer
Jürgen
J
Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
Weng
Julie
J
Kebebew
Electron
E
Soares
Paula
P
Trovisco
Vitor
V
Bastian
Boris C
BC
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
D012333:RNA, Messenger; D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf