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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. CONCLUSION:Our data indicate that the strong association between BRAF mutations and MC1R variants previously found in melanoma does not extend to thyroid cancer.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Bauer J,Weng J,Kebebew E,Soares P,Trovisco V,Bastian BC

doi

10.1111/j.1600-0625.2008.00827.x

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

548-52

issue

6

eissn

0906-6705

issn

1600-0625

pii

EXD827

journal_volume

18

pub_type

杂志文章

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