Association between endothelin receptor B nonsynonymous variants and melanoma risk.
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.
Soufir
Nadem
N
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
Meziani
Roubila
R
Lacapère
Jean-Jacques
JJ
Bertrand
Guylene
G
Fumeron
Frederic
F
Bourillon
Agnes
A
Gérard
Bénédicte
B
Descamps
Vincent
V
Crickx
Béatrice
B
Ollivaud
Laurence
L
Archimbaud
Alain
A
Lebbe
Céleste
C
Basset-Seguin
Nicole
N
Saiag
Philippe
P
Grandchamp
Bernard
B
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*
D044023:Receptor, Endothelin B