An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study.
An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma-specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.
Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
John R
JR
Davies
Sinead
S
Field
Juliette
J
Randerson-Moor
Mark
M
Harland
Rajiv
R
Kumar
Gabriella M
GM
Anic
Eduardo
E
Nagore
Johan
J
Hansson
Veronica
V
Höiom
Göran
G
Jönsson
Nelleke A
NA
Gruis
Jong Y
JY
Park
Jian
J
Guan
P
P
Sivaramakrishna Rachakonda
Judith
J
Wendt
Dace
D
Pjanova
Susana
S
Puig
Dirk
D
Schadendorf
Ichiro
I
Okamoto
Håkan
H
Olsson
Paul
P
Affleck
Zaida
Z
García-Casado
Joan Anton
JA
Puig-Butille
Alexander J
AJ
Stratigos
Elizabeth
E
Kodela
Simona
S
Donina
Antje
A
Sucker
Ismail
I
Hosen
Kathleen M
KM
Egan
Jennifer H
JH
Barrett
Remco
R
van Doorn
D Timothy
DT
Bishop
Julia
J
Newton-Bishop
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000097:blood / Q000235:genetics*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012878:Skin Neoplasms; D059405:Sun Protection Factor; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
D014809:Vitamin D-Binding Protein; D014807:Vitamin D
GC; melanoma; mendelian randomization; survival analysis; vitamin D