No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.
The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD) SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF). We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM) and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF) method in addition to Cox proportional hazards models. The Harrell's C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM), and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83) in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively). The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival.
Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, United States of America.|University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States of America.
Li
http://orcid.org/0000-0003-0728-8628
L
Luo
Department of Epidemiology and Biostatistics, Epidemiology Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Irene
I
Orlow
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.
Peter A
PA
Kanetsky
Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Nancy E
NE
Thomas
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Shenying
S
Fang
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Jeffrey E
JE
Lee
Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, United States of America.|University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States of America.
Marianne
M
Berwick
Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, United States of America.|University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States of America.
Ji-Hyun
JH
Lee
D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000453:epidemiology; D000096142:Cutaneous Malignant Melanoma
D014408:Biomarkers, Tumor; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D