The prognosis of cutaneous melanoma depends on early detection, and good biomarkers for melanoma risk may provide a valuable tool to detect melanoma development at a pre-clinical stage. By studying the epigenetic profile in pre-diagnostic blood samples of melanoma cases and cancer free controls, we aimed to identify DNA methylation sites conferring melanoma risk. DNA methylation was measured at 775,528 CpG sites using the Illumina EPIC array in whole blood in incident melanoma cases (n = 183) and matched cancer-free controls (n = 183) in the Norwegian Women and Cancer cohort. Phenotypic information and ultraviolet radiation exposure were obtained from questionnaires. Epigenome wide association (EWAS) was analyzed in future melanoma cases and controls with conditional logistic regression, with correction for multiple testing using the false discovery rate (FDR). We extended the analysis by including a public data set on melanoma (GSE120878), and combining these different data sets using a version of covariate modulated FDR (AdaPT). The analysis on future melanoma cases and controls did not identify any genome wide significant CpG sites (0.85 ≤ padj ≤ 0.99). In the restricted AdaPT analysis, 7 CpG sites were suggestive at the FDR level of 0.15. These CpG sites may potentially be used as pre-diagnostic biomarkers of melanoma risk.

Pre-diagnostic DNA methylation in blood leucocytes in cutaneous melanoma; a nested case-control study within the Norwegian Women and Cancer cohort

Vera Djordjilovic;
2022

Abstract

The prognosis of cutaneous melanoma depends on early detection, and good biomarkers for melanoma risk may provide a valuable tool to detect melanoma development at a pre-clinical stage. By studying the epigenetic profile in pre-diagnostic blood samples of melanoma cases and cancer free controls, we aimed to identify DNA methylation sites conferring melanoma risk. DNA methylation was measured at 775,528 CpG sites using the Illumina EPIC array in whole blood in incident melanoma cases (n = 183) and matched cancer-free controls (n = 183) in the Norwegian Women and Cancer cohort. Phenotypic information and ultraviolet radiation exposure were obtained from questionnaires. Epigenome wide association (EWAS) was analyzed in future melanoma cases and controls with conditional logistic regression, with correction for multiple testing using the false discovery rate (FDR). We extended the analysis by including a public data set on melanoma (GSE120878), and combining these different data sets using a version of covariate modulated FDR (AdaPT). The analysis on future melanoma cases and controls did not identify any genome wide significant CpG sites (0.85 ≤ padj ≤ 0.99). In the restricted AdaPT analysis, 7 CpG sites were suggestive at the FDR level of 0.15. These CpG sites may potentially be used as pre-diagnostic biomarkers of melanoma risk.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in ARCA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10278/5002155
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact