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Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study.
PLoS One. 2015; 10(10):e0140478.Plos

Abstract

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.

Authors+Show Affiliations

Department of Population Health, New York University School of Medicine, New York, New York, United States of America.Department of Population Health, New York University School of Medicine, New York, New York, United States of America.Department of Population Health, New York University School of Medicine, New York, New York, United States of America; New York University Cancer Institute, New York University School of Medicine, New York, New York, United States of America.Department of Molecular Medicine, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.Department of Population Health, New York University School of Medicine, New York, New York, United States of America.Department of Population Health, New York University School of Medicine, New York, New York, United States of America.Department of Oncology, Umeå University Hospital, Umeå, Sweden.Department of Population Health, New York University School of Medicine, New York, New York, United States of America; New York University Cancer Institute, New York University School of Medicine, New York, New York, United States of America; Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, United States of America.Department of Population Health, New York University School of Medicine, New York, New York, United States of America; New York University Cancer Institute, New York University School of Medicine, New York, New York, United States of America.Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Umeå, Sweden.Department of Oncology, Umeå University Hospital, Umeå, Sweden.Department of Population Health, New York University School of Medicine, New York, New York, United States of America.Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.Department of Population Health, New York University School of Medicine, New York, New York, United States of America; Radiation Effects Research Foundation, Minami-ku, Hiroshima, Japan.Department of Surgery, Umeå University Hospital, Umeå, Sweden.Department of Population Health, New York University School of Medicine, New York, New York, United States of America; New York University Cancer Institute, New York University School of Medicine, New York, New York, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26488576

Citation

Clendenen, Tess V., et al. "Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: a Nested Case-Control Study." PloS One, vol. 10, no. 10, 2015, pp. e0140478.
Clendenen TV, Ge W, Koenig KL, et al. Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study. PLoS ONE. 2015;10(10):e0140478.
Clendenen, T. V., Ge, W., Koenig, K. L., Axelsson, T., Liu, M., Afanasyeva, Y., Andersson, A., Arslan, A. A., Chen, Y., Hallmans, G., Lenner, P., Kirchhoff, T., Lundin, E., Shore, R. E., Sund, M., & Zeleniuch-Jacquotte, A. (2015). Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study. PloS One, 10(10), e0140478. https://doi.org/10.1371/journal.pone.0140478
Clendenen TV, et al. Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: a Nested Case-Control Study. PLoS ONE. 2015;10(10):e0140478. PubMed PMID: 26488576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study. AU - Clendenen,Tess V, AU - Ge,Wenzhen, AU - Koenig,Karen L, AU - Axelsson,Tomas, AU - Liu,Mengling, AU - Afanasyeva,Yelena, AU - Andersson,Anne, AU - Arslan,Alan A, AU - Chen,Yu, AU - Hallmans,Göran, AU - Lenner,Per, AU - Kirchhoff,Tomas, AU - Lundin,Eva, AU - Shore,Roy E, AU - Sund,Malin, AU - Zeleniuch-Jacquotte,Anne, Y1 - 2015/10/21/ PY - 2015/07/14/received PY - 2015/09/23/accepted PY - 2015/10/22/entrez PY - 2015/10/22/pubmed PY - 2016/7/1/medline SP - e0140478 EP - e0140478 JF - PloS one JO - PLoS ONE VL - 10 IS - 10 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26488576/Genetic_Polymorphisms_in_Vitamin_D_Metabolism_and_Signaling_Genes_and_Risk_of_Breast_Cancer:_A_Nested_Case_Control_Study_ L2 - http://dx.plos.org/10.1371/journal.pone.0140478 DB - PRIME DP - Unbound Medicine ER -