Prognostic significance of three endothelial nitric oxide synthase (eNOS) polymorphisms and metabolic syndrome (MetS) in patients with colorectal cancer

Genes Genomics. 2022 Jun;44(6):659-670. doi: 10.1007/s13258-022-01246-9. Epub 2022 Apr 4.

Abstract

Background: Polymorphisms of endothelial nitric oxide synthases (eNOS) have been associated with cancer susceptibility. Also, metabolic syndrome is associated with cancer malignancy. However, the effect of eNOS polymorphisms and metabolic syndrome on colorectal cancer (CRC) prognosis remains unclear.

Objective: To investigated whether three genetic polymorphisms (- 786 T > C rs2070744, 4a4b rs869109213, and 894G > T rs1799983) in the eNOS and metabolic syndrome (MetS) were associated with CRC patient survival.

Methods: We genotyped three polymorphisms of eNOS (- 786 T > C, 4a4b, and 894G > T) in 312 CRC cases from the Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: Although the three eNOS polymorphisms were not causative of MetS, the TT genotype of the 894G > T polymorphism was associated with a worse survival rate compared with the GG genotype in the CRC group with MetS than in the CRC group without MetS (5-years survival; adjusted HR = 54.777; 95% CI 5.073-591.487 and RFS; adjusted HR = 14.909; 95% CI 1.571-141.528).

Conclusions: The eNOS polymorphisms were not associated with metabolic syndrome prevalence in CRC patients. However, our findings suggest that the eNOS 894G > T polymorphism with MetS was associated with poor clinical outcomes.

Keywords: Colorectal cancer; Metabolic syndrome; Nitric oxide; Polymorphism; Susceptibility; eNOS.

MeSH terms

  • Colorectal Neoplasms* / complications
  • Colorectal Neoplasms* / genetics
  • Humans
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Polymorphism, Genetic
  • Prognosis

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase Type III