Integrated case-control and somatic-germline interaction analyses of melanoma susceptibility genes

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Yao YuChad D Huff

Abstract

While a number of genes have been implicated in melanoma susceptibility, the role of protein-coding variation in melanoma development and progression remains underexplored. To better characterize the role of germline coding variation in melanoma, we conducted a whole-exome case-control and somatic-germline interaction study involving 322 skin cutaneous melanoma cases from The Cancer Genome Atlas and 3607 controls of European ancestry. We controlled for cross-platform technological stratification using XPAT and conducted gene-based association tests using VAAST 2. Four established melanoma susceptibility genes achieved nominal statistical significance, MC1R (p = .0014), MITF (p = .0165) BRCA2 (p = .0206), and MTAP (p = .0393). We also observed a suggestive association for FANCA (p = .002), a gene previously implicated in melanoma survival. The association signal for BRCA2 was driven primarily by likely gene disrupting (LGD) variants, with an Odds Ratio (OR) of 5.62 (95% Confidence Interval (CI) 1.03-30.1). In contrast, the association signals for MC1R and MITF were driven primarily by predicted pathogenic missense variants, with estimated ORs of 1.4 to 3.0 for MC1R and 4.1 for MITF. MTAP exhibited an excess of both LGD and predi...Continue Reading

Citations

May 30, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Melissa RotunnoElizabeth M Gillanders
Nov 19, 2020·Trends in Genetics : TIG·Ajay ChatrathAnindya Dutta
Mar 24, 2021·The FEBS Journal·Kyoichi EbataMariko Okada
May 14, 2021·Italian Journal of Dermatology and Venereology·Sebastian PodlipnikSusana Puig

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