title: Association between endothelin receptor B nonsynonymous variants and melanoma risk.
abstract: The endothelin signaling pathway plays a crucial role in melanocyte differentiation and migration. In this study, we investigated whether germline mutations of endothelin receptor B (EDNRB), a gene involved in Hirschsprung 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.
authors.affiliation: Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Faculté de Médecine, Paris VII, Paris, France. nadem.soufir@bch.ap-hop-paris.fr
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
authors.forename: Roubila
authors.initials: R
authors.lastname: Meziani
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lacapère
authors.forename: Guylene
authors.initials: G
authors.lastname: Bertrand
authors.forename: Frederic
authors.initials: F
authors.lastname: Fumeron
authors.forename: Agnes
authors.initials: A
authors.lastname: Bourillon
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gérard
authors.forename: Vincent
authors.initials: V
authors.lastname: Descamps
authors.forename: Béatrice
authors.initials: B
authors.lastname: Crickx
authors.forename: Laurence
authors.initials: L
authors.lastname: Ollivaud
authors.forename: Alain
authors.initials: A
authors.lastname: Archimbaud
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbe
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset-Seguin
authors.forename: Philippe
authors.initials: P
authors.lastname: Saiag
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011446:Prospective Studies; D044023:Receptor, Endothelin B / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D044023:Receptor, Endothelin B