TY - CHAP
T1 - Vitamin d receptor polymorphisms and cancer
AU - Gnagnarella, Patrizia
AU - Raimondi, Sara
AU - Aristarco, Valentina
AU - Johansson, Harriet Ann
AU - Bellerba, Federica
AU - Corso, Federica
AU - Gandini, Sara
N1 - Funding Information:
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.
Publisher Copyright:
© Springer Nature Switzerland AG 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - 25-Hydroxyvitamin D
KW - Apa1
KW - Basal cell carcinoma
KW - Breast cancer
KW - Bsm1
KW - Cancer
KW - Cdx2
KW - Colon-rectum cancer
KW - Esophageal adenocarcinoma
KW - Fok1
KW - Head and neck cancer
KW - Hepatocellular carcinoma
KW - Melanoma
KW - Meta-analysis
KW - Nasopharyngeal carcinoma
KW - Non-Hodgkin lymphoma
KW - Oral squamous cell carcinoma
KW - Prostate cancer
KW - Renal cell carcinoma
KW - Risk estimates
KW - Squamous cell carcinoma
KW - Taq1
KW - Thyroid carcinoma
KW - Ultraviolet
KW - VDR polymorphisms
KW - Vitamin D
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U2 - 10.1007/978-3-030-46227-7_4
DO - 10.1007/978-3-030-46227-7_4
M3 - Chapter
C2 - 32918214
AN - SCOPUS:85090922123
T3 - Advances in Experimental Medicine and Biology
SP - 53
EP - 114
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -