Vitamin d receptor polymorphisms and cancer

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Increasing scientific evidence supports the link between vitamin D and cancer risk. The active metabolite 1,25(OH)2D exerts its activity by binding to the vitamin D receptor (VDR), an intracellular receptor that mediates transcriptional activation and repression of target genes. The binding of 1,25(OH)2D to VDR is able to regulate hundreds of different genes. VDR is active in virtually all tissues including the colon, breast, lung, ovary, bone, kidney, parathyroid gland, pancreatic b-cells, monocytes, T lymphocytes, melanocytes, keratinocytes, and also cancer cells. The relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies. We have carried out a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies considering ethnicity as a key factor for heterogeneity. Up to December 2018, we identified 176 independent studies with data to assess the risk of breast, prostate, colorectal, skin (melanoma and non-melanoma skin cancer), lung, ovarian, kidney, bladder, gallbladder, esophageal, thyroid, head and neck, liver and pancreatic cancer, oral squamous cell carcinoma, non-Hodgkin lymphoma, multiple myeloma and sarcoma. Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1, Apa1, Cdx2), breast (Fok1, Bsm1, Taq1, Apa1, CdX2), colorectal (Fok1, Bsm1, Taq1, Apa1), and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites. Conflicting data have been reported for most malignancies, and at present, it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that other factors such as ethnicity, phenotype, 25(OH)D plasma levels, and UV radiation exposure play a role as confounding factors and introduce heterogeneity. To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with assessment of vitamin D status and stratified by ethnicity.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages53-114
Number of pages62
DOIs
Publication statusPublished - 2020

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1268
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • 25-Hydroxyvitamin D
  • Apa1
  • Basal cell carcinoma
  • Breast cancer
  • Bsm1
  • Cancer
  • Cdx2
  • Colon-rectum cancer
  • Esophageal adenocarcinoma
  • Fok1
  • Head and neck cancer
  • Hepatocellular carcinoma
  • Melanoma
  • Meta-analysis
  • Nasopharyngeal carcinoma
  • Non-Hodgkin lymphoma
  • Oral squamous cell carcinoma
  • Prostate cancer
  • Renal cell carcinoma
  • Risk estimates
  • Squamous cell carcinoma
  • Taq1
  • Thyroid carcinoma
  • Ultraviolet
  • VDR polymorphisms
  • Vitamin D

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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