Cancer risks associated with the germline MITF(E318K) variant

Sci Rep. 2020 Oct 13;10(1):17051. doi: 10.1038/s41598-020-74237-z.


The MITF(E318K) variant confers moderate risk for cutaneous melanoma. While there are small studies suggesting that this risk is associated with other malignancies (e.g. renal cell carcinoma), little is known about the role of this variant in specifying risk for other cancers. In this study, we perform a systematic review and meta-analysis of the published data as a backdrop to a whole-exome sequence(WES)-based characterization of MITF(E318K) risk for various cancers in sporadic samples from the TCGA and several genetically-enriched patient cohorts. We found minimal evidence of MITF(E318K)'s contribution to non-melanoma cancer risk among individuals with low inherited risks of melanoma (OR 1.168; 95% CI 0.78-1.74; p = 0.454), suggesting that earlier reports of an association between this variant and other malignancies may be related to shared environmental or polygenic risk factors rather than MITF(E318K). Interestingly, an association was observed with uterine carcinosarcoma, (OR 9.24; 95% CI 2.08-37.17; p = 0.024), which was not previously described. While more research needs to be completed, this study will help update cancer screening recommendations for patients with the MITF(E318K) variant.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Carcinoma, Renal Cell / pathology
  • Exome Sequencing / methods
  • Genetic Predisposition to Disease
  • Germ Cells / pathology
  • Germ-Line Mutation / genetics
  • Humans
  • Melanoma / genetics
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Microphthalmia-Associated Transcription Factor / genetics*
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Neoplasms / genetics*
  • Risk Factors
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology


  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor