Association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival in the GEM study Journal Article
| Authors: | Davari, D. R.; Orlow, I.; Kanetsky, P. A.; Luo, L.; Busam, K. J.; Sharma, A.; Kricker, A.; Cust, A. E.; Anton-Culver, H.; Gruber, S. B.; Gallagher, R. P.; Zanetti, R.; Rosso, S.; Sacchetto, L.; Dwyer, T.; Gibbs, D. C.; Ollila, D. W.; Begg, C. B.; Berwick, M.; Thomas, N. E.; on behalf of the GEM Study Group |
| Article Title: | Association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival in the GEM study |
| Abstract: | Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and mel-anoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, re-spectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional haz-ards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p < 0.05) with presence of mitoses and mel-anoma-specific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted. © 2021 by the authors. |
| Keywords: | survival; single nucleotide polymorphism; melanoma; tumor-infiltrating lymphocytes; ulceration; breslow thickness; mitoses |
| Journal Title: | Current Oncology |
| Volume: | 28 |
| Issue: | 6 |
| ISSN: | 1198-0052 |
| Publisher: | Multimed Inc |
| Date Published: | 2021-12-01 |
| Start Page: | 4756 |
| End Page: | 4771 |
| Language: | English |
| DOI: | 10.3390/curroncol28060401 |
| PROVIDER: | scopus |
| PMCID: | PMC8628692 |
| PUBMED: | 34898573 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2021 -- Source: Scopus |
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