Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study.
Inherited MC1R variants modulate MITF transcription factor signaling, which in turn affects tumor cell proliferation, apoptosis, and DNA repair. The aim of this BioGenoMEL collaborative study in 10 melanoma cohorts was to test the hypothesis that inherited variants thereby moderate survival expectation. A survival analysis in the largest cohort (Leeds) was carried out adjusting for factors known to impact on survival. The results were then compared with data from nine smaller cohorts. The absence of any consensus MC1R alleles was associated with a significantly lower risk of death in the Leeds set (HR, 0.64; 95% CI, 0.46-0.89) and overall in the 10 data sets (HR, 0.78; 95% CI, 0.65-0.94) with some support from the nine smaller data sets considered together (HR, 0.83; 95% CI, 0.67-1.04). The data are suggestive of a survival benefit for inherited MC1R variants in melanoma patients.
Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. j.r.davies@leeds.ac.uk
John R
JR
Davies
Juliette
J
Randerson-Moor
Kairen
K
Kukalizch
Mark
M
Harland
Rajiv
R
Kumar
Srinivasan
S
Madhusudan
Eduardo
E
Nagore
Johan
J
Hansson
Veronica
V
Höiom
Paola
P
Ghiorzo
Nelleke A
NA
Gruis
Peter A
PA
Kanetsky
Judith
J
Wendt
Dace
D
Pjanova
Susana
S
Puig
Philippe
P
Saiag
Dirk
D
Schadendorf
Nadem
N
Soufir
Ichiro
I
Okamoto
Paul
P
Affleck
Zaida
Z
García-Casado
Zighereda
Z
Ogbah
Aija
A
Ozola
Paola
P
Queirolo
Antje
A
Sucker
Jennifer H
JH
Barrett
Remco
R
van Doorn
D Timothy
DT
Bishop
Julia
J
Newton-Bishop
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006200:Hair Color / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality*; D008875:Middle Aged; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult
D044102:Receptor, Melanocortin, Type 1