1. Association Between Endothelin Receptor B Nonsynonymous Variants and Melanoma Risk.
- Author
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Soufir, Nadem, Meziani, Roubila, Lacapère, Jean-Jacques, Bertrand, Guylene, Fumeron, Frederic, Bourillon, Agnes, Gérard, Bénédicte, Descamps, Vincent, Crickx, Béatrice, Ollivaud, Laurence, Archimbaud, Alain, Lebbe, Céleste, Basset-Seguin, Nicole, Saiag, Philippe, and Grandchamp, Bernard
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ENDOTHELINS , *PEPTIDES , *MELANOMA , *MELANOCYTES , *EPITHELIAL cells , *HIRSCHSPRUNG'S disease , *CANCER - Abstract
The endothelin signaling pathway plays a crucial role in melanocyte differentiation and migration. In this study, we investigated whether germ-line mutations of endothelin receptor B (EDNRB), a gene involved in Hirsch-sprung disease (HSCR), could also predispose for malignant melanoma (MM). The coding region of EDNRB was sequenced in 137 MM patients and in 130 ethnically matched Caucasian control subjects. Six nonsynonymous EDNRB variants were found in 15 patients (11%), but only two were found in four control subjects (3%, odds ratio [OR] = 3.87, 95% confidence interval [CI] = 1.25 to 12; P = .012). Overall, 14 out of 15 MM patients carried EDNRB mutations reported in HSCR, some of which had previously been shown to lead to loss of function. In multivariable logistic regression analysis including skin type, eye and hair color, number of nevi, and dorsal lentigines (freckles), the association between EDNRB mutations and MM risk remained statistically significant (OR = 19.9, 95% CI = 1.34 to 296.2; P = .03). Our data strongly suggest that EDNRB is involved in predisposition for two different multigenic disorders, HSCR and melanoma. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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