. 2018 Nov;138(11):2398-2404.

doi: 10.1016/j.jid.2018.04.025. Epub 2018 May 9.

Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Nancy E Thomas¹, Sharon N Edmiston², Irene Orlow³, Peter A Kanetsky⁴, Li Luo⁵, David C Gibbs⁶, Eloise A Parrish², Honglin Hao⁷, Klaus J Busam⁸, Bruce K Armstrong⁹, Anne Kricker¹⁰, Anne E Cust¹¹, Hoda Anton-Culver¹², Stephen B Gruber¹³, Richard P Gallagher¹⁴, Roberto Zanetti¹⁵, Stefano Rosso¹⁵, Lidia Sacchetto¹⁶, Terence Dwyer¹⁷, David W Ollila¹⁸, Colin B Begg³, Marianne Berwick⁵, Kathleen Conway¹⁹; GEM Study Group

Collaborators, Affiliations

Collaborators

Affiliations

¹ Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. Electronic address: nthomas@med.unc.edu.
² Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
³ Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA.
⁴ Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
⁵ Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, New Mexico, USA.
⁶ Department of Epidemiology, Emory University, Atlanta, Georgia, USA.
⁷ Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA.
⁸ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, USA.
⁹ School of Public and Global Health, The University of Western Australia, Perth, Australia.
¹⁰ Sydney School of Public Health, The University of Sydney, Sydney, Australia.
¹¹ Sydney School of Public Health, The University of Sydney, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, North Sydney, Australia.
¹² Department of Epidemiology, University of California, Irvine, California, USA.
¹³ USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
¹⁴ British Columbia Cancer and Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
¹⁶ Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy; Politecnico di Torino, Turin, Italy.
¹⁷ George Institute for Global Health, Nuffield Department of Obstetrics and Gynecology, University of Oxford, Oxford, UK.
¹⁸ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
¹⁹ Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.

PMID: 29753029
PMCID: PMC6200630
DOI: 10.1016/j.jid.2018.04.025

Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Nancy E Thomas et al. J Invest Dermatol. 2018 Nov.

. 2018 Nov;138(11):2398-2404.

doi: 10.1016/j.jid.2018.04.025. Epub 2018 May 9.

Authors

Collaborators

Affiliations

¹ Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. Electronic address: nthomas@med.unc.edu.
² Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
³ Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA.
⁴ Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
⁵ Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, New Mexico, USA.
⁶ Department of Epidemiology, Emory University, Atlanta, Georgia, USA.
⁷ Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA.
⁸ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, USA.
⁹ School of Public and Global Health, The University of Western Australia, Perth, Australia.
¹⁰ Sydney School of Public Health, The University of Sydney, Sydney, Australia.
¹¹ Sydney School of Public Health, The University of Sydney, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, North Sydney, Australia.
¹² Department of Epidemiology, University of California, Irvine, California, USA.
¹³ USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
¹⁴ British Columbia Cancer and Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
¹⁶ Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy; Politecnico di Torino, Turin, Italy.
¹⁷ George Institute for Global Health, Nuffield Department of Obstetrics and Gynecology, University of Oxford, Oxford, UK.
¹⁸ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
¹⁹ Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.

PMID: 29753029
PMCID: PMC6200630
DOI: 10.1016/j.jid.2018.04.025

Abstract

BRAF and NRAS mutations arise early in melanoma development, but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma Study, 1,223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms identified as low-penetrant melanoma-risk variants. We used multinomial logistic regression to simultaneously examine each single-nucleotide polymorphism's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features. IRF4 rs12203592*T was associated with BRAF V600E (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.43-0.79) and V600K (OR = 0.65, 95% CI = 0.41-1.03), but not BRAF other or NRAS+ melanoma. A global test of etiologic heterogeneity (P_global = 0.001) passed false discovery (P_global = 0.0026). PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma. The test for etiologic heterogeneity (P_global) was 0.005. The IRF4 rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6 rs132985 associations were independent of phenotypes. IRF4 and PLA2G6 inherited genotypes may influence melanoma BRAF/NRAS subtype development.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

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Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Collaborators

Affiliations

Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous