학술논문

Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death.
Document Type
Academic Journal
Author
Gibbs DC; Department of Dermatology, Emory University, Atlanta, GA, USA.; Thomas NE; Department of Dermatology, University of North Carolina, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.; Kanetsky PA; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.; Luo L; Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM, USA.; Busam KJ; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cust AE; Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia.; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.; Anton-Culver H; Department of Epidemiology, University of California, Irvine, CA, USA.; Gallagher RP; Cancer Control Research, British Columbia Cancer and Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.; Zanetti R; Center for Cancer Prevention, Piedmont Cancer Registry, Torino, Italy.; Fondo Elena Moroni for Oncology, Torino, Italy.; Department of Surgery, University of North Carolina, Chapel Hill, NC, USA.; Rosso S; Center for Cancer Prevention, Piedmont Cancer Registry, Torino, Italy.; Fondo Elena Moroni for Oncology, Torino, Italy.; Department of Surgery, University of North Carolina, Chapel Hill, NC, USA.; Sacchetto L; Center for Cancer Prevention, Piedmont Cancer Registry, Torino, Italy.; Fondo Elena Moroni for Oncology, Torino, Italy.; Department of Surgery, University of North Carolina, Chapel Hill, NC, USA.; Edmiston SN; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.; Conway K; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.; Department of Epidemiology, Gillings Global School of Public Health, University of North Carolina, Chapel Hill, NC, USA.; Ollila DW; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.; Department of Surgery, University of North Carolina, Chapel Hill, NC, USA.; Begg CB; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Berwick M; Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM, USA.; Ward SV; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.; Orlow I; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 101721827 Publication Model: Print Cited Medium: Internet ISSN: 2515-5091 (Electronic) Linking ISSN: 25155091 NLM ISO Abbreviation: JNCI Cancer Spectr Subsets: MEDLINE
Subject
Language
English
Abstract
Background: It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear.
Methods: We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression.
Results: In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (Pinteraction = .003).
Conclusions: Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-than individuals without this Gc1f haplotype.
(© The Author(s) 2023. Published by Oxford University Press.)