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Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study

1
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA
2
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
3
Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
4
Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM 87102, USA
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
6
Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia
7
Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, NSW 2006, Australia
8
Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia
9
Department of Medicine, University of California, Irvine, CA 92697, USA
10
City of Hope National Medical Center, Duarte, CA 91010, USA
11
BC Cancer and Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC V5Z 1L3, Canada
12
Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, 10156 Turin, Italy
13
Murdoch Children’s Research Institute, Melbourne, VIC 3052, Australia
14
The Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK
15
Department of Pediatrics, University of Melbourne, Melbourne, VIC 3010, Australia
16
Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK
17
School of Medicine, Emory University, Atlanta, GA 30322, USA
18
Department of Surgery, University of North Carolina, Chapel Hill, NC 27599, USA
19
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
GEM Study Group members are listed in acknowledgments.
Curr. Oncol. 2021, 28(6), 4756-4771; https://doi.org/10.3390/curroncol28060401
Received: 11 August 2021 / Revised: 11 October 2021 / Accepted: 10 November 2021 / Published: 16 November 2021
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. View Full-Text
Keywords: melanoma; single nucleotide polymorphism; Breslow thickness; ulceration; mitoses; tumor-infiltrating lymphocytes; survival melanoma; single nucleotide polymorphism; Breslow thickness; ulceration; mitoses; tumor-infiltrating lymphocytes; survival
MDPI and ACS Style

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 Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study. Curr. Oncol. 2021, 28, 4756-4771. https://doi.org/10.3390/curroncol28060401

AMA Style

Davari DR, Orlow I, Kanetsky PA, Luo L, Busam KJ, Sharma A, Kricker A, Cust AE, Anton-Culver H, Gruber SB, Gallagher RP, Zanetti R, Rosso S, Sacchetto L, Dwyer T, Gibbs DC, Ollila DW, Begg CB, Berwick M, Thomas NE on behalf of the GEM Study Group. Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study. Current Oncology. 2021; 28(6):4756-4771. https://doi.org/10.3390/curroncol28060401

Chicago/Turabian Style

Davari, Danielle R., Irene Orlow, Peter A. Kanetsky, Li Luo, Klaus J. Busam, Ajay Sharma, Anne Kricker, Anne E. Cust, Hoda Anton-Culver, Stephen B. Gruber, Richard P. Gallagher, Roberto Zanetti, Stefano Rosso, Lidia Sacchetto, Terence Dwyer, David C. Gibbs, David W. Ollila, Colin B. Begg, Marianne Berwick, and Nancy E. Thomas on behalf of the GEM Study Group 2021. "Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study" Current Oncology 28, no. 6: 4756-4771. https://doi.org/10.3390/curroncol28060401

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