Vitamin D Signaling Pathways Confer the Susceptibility of Esophageal Squamous Cell Carcinoma in a Northern Chinese Population

Nutr Cancer. 2017 May-Jun;69(4):593-600. doi: 10.1080/01635581.2017.1299873. Epub 2017 Mar 31.

Abstract

Experimental studies have determined the chemopreventive effects of vitamin D against the esophageal squamous cell carcinoma (ESCC); however, results from the epidemiological studies are not yet well established. The current study aimed to evaluate the associations between plasma vitamin D levels and variants on vitamin D metabolic-related genes with the risks for ESCC. A hospital-based case-control study was performed. Five hundred eighty-two ESCC patients and 569 controls were recruited in a Northern Chinese population. Common variants on vitamin D metabolism-related genes CYP24A1, DHCR7, GC, CYP27B1, and vitamin D receptor (VDR) and the plasma 25(OH)D level were determined. The unconditional logistic regression method was applied to determine the associations between the variants and vitamin D level and ESCC. Higher plasma 25(OH)D was associated with a reduced risk for ESCC, especially for rs2296241, rs11568820, and rs4646536. The variants rs2296241 on CYP24A1 and rs11568820 on VDR are significantly associated with ESCC cancer. Vitamin D signaling pathways may participate in the ESCC development. Further studies with larger sample size are warranted to confirm the results. Intervention studies are needed to determine whether vitamin D supplementation may reduce the ESCC risk in the Chinese population.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Aged
  • Asian People / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • DNA-Binding Proteins / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood*
  • Vitamin D / genetics
  • Vitamin D / metabolism
  • Vitamin D3 24-Hydroxylase / genetics

Substances

  • DBP protein, human
  • DNA-Binding Proteins
  • Receptors, Calcitriol
  • Transcription Factors
  • VDR protein, human
  • Vitamin D
  • 25-hydroxyvitamin D
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase