Polymorphisms in VDR, CYP27B1, CYP2R1, GC and CYP24A1 Genes as Biomarkers of Survival in Non-Small Cell Lung Cancer: A Systematic Review

Nutrients. 2023 Mar 21;15(6):1525. doi: 10.3390/nu15061525.

Abstract

The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in the genes involved in the metabolic pathway of vitamin D and overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). This systematic review was conducted in accordance with the PRISMA guidelines. It included all the literature published up to 1 November 2022 and was carried out in four databases (Medline [PubMed], Scopus, Web of Science, and Embase), using the PICO strategy, with relevant keywords related to the objective. The quality of the studies included was evaluated with an assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Six studies were included in this systematic review. Our findings showed that the BsmI (rs1544410), Cdx-2 (rs11568820), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236), rs4646536, rs6068816, rs7041, and rs10741657 SNPs in the genes that play a part in vitamin D synthesis (CYP2R1, CYP27B1), transport (GC), and metabolism (CYP24A1), as well as in the vitamin D receptor (VDR), are associated with OS and/or PFS in patients with NSCLC. The SNPs in VDR have been the most extensively analyzed. This systematic review summed up the available evidence concerning the association between 13 SNPs in the main genes involved in the vitamin D metabolic pathway and prognosis in NSCLC. It revealed that SNPs in the VDR, CYP27B1, CYP24A1, GC, and CYP2R1 genes could have an impact on survival in this disease. These findings suggest the identification of prognostic biomarkers in NSCLC patients. However, evidence remains sparse for each of the polymorphisms examined, so these findings should be treated with caution.

Keywords: CYP24A1; CYP27B1; CYP2R1; GC; VDR; non-small cell lung cancer; overall survival; progression-free survival; single-nucleotide polymorphisms; vitamin D.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Case-Control Studies
  • Cytochrome P450 Family 2 / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lung Neoplasms* / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics
  • Vitamin D
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamins

Substances

  • Receptors, Calcitriol
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Vitamin D3 24-Hydroxylase
  • Vitamin D
  • Biomarkers
  • Vitamins
  • CYP27B1 protein, human
  • CYP2R1 protein, human
  • Cytochrome P450 Family 2
  • VDR protein, human
  • CYP24A1 protein, human