Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death Journal Article
| Authors: | Gibbs, D. C.; Thomas, N. E.; Kanetsky, P. A.; Luo, L.; Busam, K. J.; Cust, A. E.; Anton-Culver, H.; Gallagher, R. P.; Zanetti, R.; Rosso, S.; Sacchetto, L.; Edmiston, S. N.; Conway, K.; Ollila, D. W.; Begg, C. B.; Berwick, M.; Ward, S. V.; Orlow, I. |
| Article Title: | Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death |
| 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. |
| Keywords: | survival; phenotype; progression; health; precursor; design; cancer-risk; gc; prognosis; macrophage-activating factor |
| Journal Title: | JNCI Cancer Spectrum |
| Volume: | 7 |
| Issue: | 5 |
| ISSN: | 2515-5091 |
| Publisher: | Oxford University Press |
| Date Published: | 2023-10-01 |
| Start Page: | pkad051 |
| Language: | English |
| ACCESSION: | WOS:001064252500001 |
| DOI: | 10.1093/jncics/pkad051 |
| PROVIDER: | wos |
| PMCID: | PMC10496570 |
| PUBMED: | 37494457 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Irene Orlow -- Source: Wos |
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