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.
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: Meg R Gerstenblith; Alisa M Goldstein; Maria Concetta Fargnoli; Ketty Peris; Maria Teresa Landi Journal: Hum Mutat Date: 2007-05 Impact factor: 4.878
Authors: Andrew I Su; Tim Wiltshire; Serge Batalov; Hilmar Lapp; Keith A Ching; David Block; Jie Zhang; Richard Soden; Mimi Hayakawa; Gabriel Kreiman; Michael P Cooke; John R Walker; John B Hogenesch Journal: Proc Natl Acad Sci U S A Date: 2004-04-09 Impact factor: 11.205
Authors: Helen Davies; Graham R Bignell; Charles Cox; Philip Stephens; Sarah Edkins; Sheila Clegg; Jon Teague; Hayley Woffendin; Mathew J Garnett; William Bottomley; Neil Davis; Ed Dicks; Rebecca Ewing; Yvonne Floyd; Kristian Gray; Sarah Hall; Rachel Hawes; Jaime Hughes; Vivian Kosmidou; Andrew Menzies; Catherine Mould; Adrian Parker; Claire Stevens; Stephen Watt; Steven Hooper; Rebecca Wilson; Hiran Jayatilake; Barry A Gusterson; Colin Cooper; Janet Shipley; Darren Hargrave; Katherine Pritchard-Jones; Norman Maitland; Georgia Chenevix-Trench; Gregory J Riggins; Darell D Bigner; Giuseppe Palmieri; Antonio Cossu; Adrienne Flanagan; Andrew Nicholson; Judy W C Ho; Suet Y Leung; Siu T Yuen; Barbara L Weber; Hilliard F Seigler; Timothy L Darrow; Hugh Paterson; Richard Marais; Christopher J Marshall; Richard Wooster; Michael R Stratton; P Andrew Futreal Journal: Nature Date: 2002-06-09 Impact factor: 49.962
Authors: Alexander I Kuklin; Randall L Mynatt; Mitchell L Klebig; Laura L Kiefer; William O Wilkison; Richard P Woychik; Edward J Michaud Journal: Mol Cancer Date: 2004-06-02 Impact factor: 27.401