Genetic Analysis Identifies the Role of HLF in Renal Cell Carcinoma

Cancer Genomics Proteomics. 2020 Nov-Dec;17(6):827-833. doi: 10.21873/cgp.20236.


Background/aim: Circadian rhythm is an internal clock that regulates the cycles of many biological functions. Epidemiological studies have linked aberrant circadian rhythm to an increased susceptibility to cancer and poor patient prognosis. However, there remains a gap in our understanding of genetic variants related to the circadian pathway in renal cell carcinoma (RCC) progression.

Patients and methods: We examined the associations of 150 single nucleotide polymorphisms (SNPs) in 12 core circadian pathway genes with RCC risk and survival in 630 patients with RCC and controls.

Results: After adjusting for multiple comparisons and performing multivariate analyses, we found that the HLF rs6504958 polymorphism was significantly associated with RCC risk (q<0.05), whereas, no SNP association was significant for survival. Furthermore, the rs6504958 G allele was associated with reduced expression of HLF; consequently, a lower HLF expression was correlated with more advanced RCC. Moreover, a meta-analysis of six kidney cancer gene expression datasets demonstrated that an elevated HLF expression was associated with a favorable prognosis in patients with RCC (hazard ratio=0.70, 95% confidence interval=0.65-0.76, p<0.001).

Conclusion: These findings implicate the potential protective role of HLF in the progression of RCC.

Keywords: Renal cell carcinoma; circadian rhythm; metastasis-free survival; overall survival; single nucleotide polymorphism.

MeSH terms

  • Aged
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Survival Rate


  • Basic-Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • HLF protein, human