Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study

Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the...

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Published in:PLOS ONE
Main Authors: Clendenen, Tess V., Ge, Wenzhen, Koenig, Karen L., Axelsson, Tomas, Liu, Mengling, Afanasyeva, Yelena, Andersson, Anne, Arslan, Alan A., Chen, Yu, Hallmans, Göran, Lenner, Per, Kirchhoff, Tomas, Lundin, Eva, Shore, Roy E., Sund, Malin, Zeleniuch-Jacquotte, Anne
Format: Article in Journal/Newspaper
Language:English
Published: Umeå universitet, Näringsforskning 2015
Subjects:
Online Access:http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111478
https://doi.org/10.1371/journal.pone.0140478
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spelling ftumeauniv:oai:DiVA.org:umu-111478 2023-10-09T21:54:35+02:00 Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study Clendenen, Tess V. Ge, Wenzhen Koenig, Karen L. Axelsson, Tomas Liu, Mengling Afanasyeva, Yelena Andersson, Anne Arslan, Alan A. Chen, Yu Hallmans, Göran Lenner, Per Kirchhoff, Tomas Lundin, Eva Shore, Roy E. Sund, Malin Zeleniuch-Jacquotte, Anne 2015 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111478 https://doi.org/10.1371/journal.pone.0140478 eng eng Umeå universitet, Näringsforskning Umeå universitet, Patologi PLOS one PLOS ONE, 2015, 10:10, orcid:0000-0001-9581-3845 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111478 doi:10.1371/journal.pone.0140478 PMID 26488576 ISI:000363248400054 Scopus 2-s2.0-84949494365 info:eu-repo/semantics/openAccess Cancer and Oncology Cancer och onkologi Cell and Molecular Biology Cell- och molekylärbiologi Article in journal info:eu-repo/semantics/article text 2015 ftumeauniv https://doi.org/10.1371/journal.pone.0140478 2023-09-22T13:58:01Z Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) PLOS ONE 10 10 e0140478
institution Open Polar
collection Umeå University: Publications (DiVA)
op_collection_id ftumeauniv
language English
topic Cancer and Oncology
Cancer och onkologi
Cell and Molecular Biology
Cell- och molekylärbiologi
spellingShingle Cancer and Oncology
Cancer och onkologi
Cell and Molecular Biology
Cell- och molekylärbiologi
Clendenen, Tess V.
Ge, Wenzhen
Koenig, Karen L.
Axelsson, Tomas
Liu, Mengling
Afanasyeva, Yelena
Andersson, Anne
Arslan, Alan A.
Chen, Yu
Hallmans, Göran
Lenner, Per
Kirchhoff, Tomas
Lundin, Eva
Shore, Roy E.
Sund, Malin
Zeleniuch-Jacquotte, Anne
Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
topic_facet Cancer and Oncology
Cancer och onkologi
Cell and Molecular Biology
Cell- och molekylärbiologi
description Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
format Article in Journal/Newspaper
author Clendenen, Tess V.
Ge, Wenzhen
Koenig, Karen L.
Axelsson, Tomas
Liu, Mengling
Afanasyeva, Yelena
Andersson, Anne
Arslan, Alan A.
Chen, Yu
Hallmans, Göran
Lenner, Per
Kirchhoff, Tomas
Lundin, Eva
Shore, Roy E.
Sund, Malin
Zeleniuch-Jacquotte, Anne
author_facet Clendenen, Tess V.
Ge, Wenzhen
Koenig, Karen L.
Axelsson, Tomas
Liu, Mengling
Afanasyeva, Yelena
Andersson, Anne
Arslan, Alan A.
Chen, Yu
Hallmans, Göran
Lenner, Per
Kirchhoff, Tomas
Lundin, Eva
Shore, Roy E.
Sund, Malin
Zeleniuch-Jacquotte, Anne
author_sort Clendenen, Tess V.
title Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
title_short Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
title_full Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
title_fullStr Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
title_full_unstemmed Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
title_sort genetic polymorphisms in vitamin d metabolism and signaling genes and risk of breast cancer : a nested case-control study
publisher Umeå universitet, Näringsforskning
publishDate 2015
url http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111478
https://doi.org/10.1371/journal.pone.0140478
genre Northern Sweden
genre_facet Northern Sweden
op_relation PLOS ONE, 2015, 10:10,
orcid:0000-0001-9581-3845
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111478
doi:10.1371/journal.pone.0140478
PMID 26488576
ISI:000363248400054
Scopus 2-s2.0-84949494365
op_rights info:eu-repo/semantics/openAccess
op_doi https://doi.org/10.1371/journal.pone.0140478
container_title PLOS ONE
container_volume 10
container_issue 10
container_start_page e0140478
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