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Cancer risks associated with the germline MITF(E318K) variant

Samantha M Guhan1, Mykyta Artomov2, Shelley McCormick3

  • 1Wellman Center for Photomedicine at Massachusetts General Hospital, Edwards 211, 50 Blossom Street, Boston, MA, 02114, USA.

Scientific Reports
|October 14, 2020
PubMed

Insights

The MITF(E318K) variant primarily increases cutaneous melanoma risk. This study found minimal evidence for other cancer risks, except for a novel association with uterine carcinosarcoma.

Area of Science:

  • Genetics
  • Oncology
  • Genomic Medicine

Background:

  • The MITF(E318K) variant is a known risk factor for cutaneous melanoma.
  • Limited data exists on its association with other cancer types.
  • Previous studies suggested links to malignancies like renal cell carcinoma, but lacked comprehensive analysis.

Purpose of the Study:

  • To systematically review and meta-analyze existing data on MITF(E318K) and cancer risk.
  • To characterize the risk of MITF(E318K) for various cancers using whole-exome sequencing data.
  • To clarify the role of MITF(E318K) in non-melanoma cancer predisposition.

Main Methods:

  • Systematic review and meta-analysis of published literature.
  • Whole-exome sequencing (WES) analysis of sporadic cancer samples from The Cancer Genome Atlas (TCGA).
  • Analysis of genetically-enriched patient cohorts.

Main Results:

  • Minimal evidence supports MITF(E318K) contribution to non-melanoma cancer risk in low-risk individuals (OR 1.168, p=0.454).
  • An unexpected significant association was found between MITF(E318K) and uterine carcinosarcoma (OR 9.24, p=0.024).
  • Findings suggest prior associations with other malignancies may stem from shared environmental or polygenic factors.

Conclusions:

  • The MITF(E318K) variant's primary role is in melanoma risk, with limited evidence for other cancers.
  • A novel association with uterine carcinosarcoma warrants further investigation.
  • Results may inform updated cancer screening guidelines for individuals carrying the MITF(E318K) variant.

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