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Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study
INTRODUCTION: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD lev...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446393/ https://www.ncbi.nlm.nih.gov/pubmed/22480149 http://dx.doi.org/10.1186/bcr3162 |
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author | Yao, Song Zirpoli, Gary Bovbjerg, Dana H Jandorf, Lina Hong, Chi Chen Zhao, Hua Sucheston, Lara E Tang, Li Roberts, Michelle Ciupak, Gregory Davis, Warren Hwang, Helena Johnson, Candace S Trump, Donald L McCann, Susan E Ademuyiwa, Foluso Pawlish, Karen S Bandera, Elisa V Ambrosone, Christine B |
author_facet | Yao, Song Zirpoli, Gary Bovbjerg, Dana H Jandorf, Lina Hong, Chi Chen Zhao, Hua Sucheston, Lara E Tang, Li Roberts, Michelle Ciupak, Gregory Davis, Warren Hwang, Helena Johnson, Candace S Trump, Donald L McCann, Susan E Ademuyiwa, Foluso Pawlish, Karen S Bandera, Elisa V Ambrosone, Christine B |
author_sort | Yao, Song |
collection | PubMed |
description | INTRODUCTION: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics. METHODS: In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status. RESULTS: More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs. CONCLUSIONS: These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women. |
format | Online Article Text |
id | pubmed-3446393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34463932012-09-20 Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study Yao, Song Zirpoli, Gary Bovbjerg, Dana H Jandorf, Lina Hong, Chi Chen Zhao, Hua Sucheston, Lara E Tang, Li Roberts, Michelle Ciupak, Gregory Davis, Warren Hwang, Helena Johnson, Candace S Trump, Donald L McCann, Susan E Ademuyiwa, Foluso Pawlish, Karen S Bandera, Elisa V Ambrosone, Christine B Breast Cancer Res Research Article INTRODUCTION: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics. METHODS: In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status. RESULTS: More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs. CONCLUSIONS: These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women. BioMed Central 2012 2012-04-04 /pmc/articles/PMC3446393/ /pubmed/22480149 http://dx.doi.org/10.1186/bcr3162 Text en Copyright ©2012 Yao et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yao, Song Zirpoli, Gary Bovbjerg, Dana H Jandorf, Lina Hong, Chi Chen Zhao, Hua Sucheston, Lara E Tang, Li Roberts, Michelle Ciupak, Gregory Davis, Warren Hwang, Helena Johnson, Candace S Trump, Donald L McCann, Susan E Ademuyiwa, Foluso Pawlish, Karen S Bandera, Elisa V Ambrosone, Christine B Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study |
title | Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study |
title_full | Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study |
title_fullStr | Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study |
title_full_unstemmed | Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study |
title_short | Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study |
title_sort | variants in the vitamin d pathway, serum levels of vitamin d, and estrogen receptor negative breast cancer among african-american women: a case-control study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446393/ https://www.ncbi.nlm.nih.gov/pubmed/22480149 http://dx.doi.org/10.1186/bcr3162 |
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