Cargando…
Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study
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 melanoma-specific survival. The...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628692/ https://www.ncbi.nlm.nih.gov/pubmed/34898573 http://dx.doi.org/10.3390/curroncol28060401 |
_version_ | 1784607048130887680 |
---|---|
author | Davari, Danielle R. Orlow, Irene Kanetsky, Peter A. Luo, Li Busam, Klaus J. Sharma, Ajay Kricker, Anne Cust, Anne E. Anton-Culver, Hoda Gruber, Stephen B. Gallagher, Richard P. Zanetti, Roberto Rosso, Stefano Sacchetto, Lidia Dwyer, Terence Gibbs, David C. Ollila, David W. Begg, Colin B. Berwick, Marianne Thomas, Nancy E. |
author_facet | Davari, Danielle R. Orlow, Irene Kanetsky, Peter A. Luo, Li Busam, Klaus J. Sharma, Ajay Kricker, Anne Cust, Anne E. Anton-Culver, Hoda Gruber, Stephen B. Gallagher, Richard P. Zanetti, Roberto Rosso, Stefano Sacchetto, Lidia Dwyer, Terence Gibbs, David C. Ollila, David W. Begg, Colin B. Berwick, Marianne Thomas, Nancy E. |
author_sort | Davari, Danielle R. |
collection | PubMed |
description | 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 melanoma-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, respectively, 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 hazards 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 melanoma-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. |
format | Online Article Text |
id | pubmed-8628692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86286922021-11-30 Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study Davari, Danielle R. Orlow, Irene Kanetsky, Peter A. Luo, Li Busam, Klaus J. Sharma, Ajay Kricker, Anne Cust, Anne E. Anton-Culver, Hoda Gruber, Stephen B. Gallagher, Richard P. Zanetti, Roberto Rosso, Stefano Sacchetto, Lidia Dwyer, Terence Gibbs, David C. Ollila, David W. Begg, Colin B. Berwick, Marianne Thomas, Nancy E. Curr Oncol Communication 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 melanoma-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, respectively, 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 hazards 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 melanoma-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. MDPI 2021-11-16 /pmc/articles/PMC8628692/ /pubmed/34898573 http://dx.doi.org/10.3390/curroncol28060401 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Davari, Danielle R. Orlow, Irene Kanetsky, Peter A. Luo, Li Busam, Klaus J. Sharma, Ajay Kricker, Anne Cust, Anne E. Anton-Culver, Hoda Gruber, Stephen B. Gallagher, Richard P. Zanetti, Roberto Rosso, Stefano Sacchetto, Lidia Dwyer, Terence Gibbs, David C. Ollila, David W. Begg, Colin B. Berwick, Marianne Thomas, Nancy E. Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study |
title | Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study |
title_full | Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study |
title_fullStr | Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study |
title_full_unstemmed | Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study |
title_short | Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study |
title_sort | association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival in the gem study |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628692/ https://www.ncbi.nlm.nih.gov/pubmed/34898573 http://dx.doi.org/10.3390/curroncol28060401 |
work_keys_str_mv | AT davaridanieller associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT orlowirene associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT kanetskypetera associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT luoli associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT busamklausj associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT sharmaajay associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT krickeranne associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT custannee associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT antonculverhoda associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT gruberstephenb associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT gallagherrichardp associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT zanettiroberto associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT rossostefano associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT sacchettolidia associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT dwyerterence associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT gibbsdavidc associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT olliladavidw associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT beggcolinb associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT berwickmarianne associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy AT thomasnancye associationofmelanomariskvariantswithprimarymelanomatumorprognosticcharacteristicsandmelanomaspecificsurvivalinthegemstudy |