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Vitamin D Receptor Polymorphisms and Cancer

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Sunlight, Vitamin D and Skin Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1268))

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.

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Abbreviations

BCC:

Basal cell carcinoma

BMI:

Body mass index

CI:

Confidence interval

CRC:

Colorectal cancer

EAC:

Esophageal adenocarcinoma

HCC:

Hepatocellular carcinoma

HNC:

Head and neck cancer

H-W:

Hardy-Weinberg

MM:

Malignant melanoma

NHL:

Non-Hodgkin lymphoma

NMSC:

Non-melanoma skin cancer

NPC:

Nasopharyngeal carcinoma

OR:

Odds ratio

OSCC:

Oral squamous cell carcinoma

PCa:

Prostate cancer

RCC:

Renal cell carcinoma

RFLP:

Restriction fragment length polymorphism

RR:

Relative risk

SCC:

Squamous cell carcinoma

SNP:

Single nucleotide polymorphism

SRR:

Summary relative risk

TC:

Thyroid carcinoma

UV:

Ultraviolet

VDR:

Vitamin D receptor

vs:

Versus

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Acknowledgments

We thank the Fondazione Umberto Veronesi (FUV) and Italian Association Against Cancer for the financial support. This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds.

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Authors and Affiliations

  1. Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCSS, Milan, Italy

    Patrizia Gnagnarella

  2. Department of Experimental Oncology, IEO European Institute of Oncology IRCSS, Milan, Italy

    Sara Raimondi, Federica Bellerba, Federica Corso & Sara Gandini

  3. Division of Cancer Prevention and Genetics, IEO European Institute of Oncology IRCSS, Milan, Italy

    Valentina Aristarco & Harriet Ann Johansson

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  1. Patrizia Gnagnarella
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Correspondence to Sara Gandini .

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  1. Center for Clinical and Experimental Photodermatology and Department of Dermatology, Saarland University Medical Center, Homburg, Germany

    Jörg Reichrath

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Gnagnarella, P. et al. (2020). Vitamin D Receptor Polymorphisms and Cancer. In: Reichrath, J. (eds) Sunlight, Vitamin D and Skin Cancer. Advances in Experimental Medicine and Biology, vol 1268. Springer, Cham. https://doi.org/10.1007/978-3-030-46227-7_4

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