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

Song Yao, Gary Zirpoli, Dana H. Bovbjerg, Lina Jandorf, Chi Chen Hong, Hua Zhao, Lara E. Sucheston, Li Tang, Michelle Roberts, Gregory Ciupak, Warren Davis, Helena Hwang, Candace S. Johnson, Donald L. Trump, Susan E. McCann, Foluso Ademuyiwa, Karen S. Pawlish, Elisa V. Bandera, Christine B. Ambrosone

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numberR58
JournalBreast Cancer Research
Volume14
Issue number2
DOIs
StatePublished - Apr 4 2012

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Calcitriol Receptors
Vitamin D
Estrogen Receptors
African Americans
Case-Control Studies
Breast Neoplasms
Serum
Single Nucleotide Polymorphism
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Vitamin D Deficiency
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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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. / 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.

In: Breast Cancer Research, Vol. 14, No. 2, R58, 04.04.2012.

Research output: Contribution to journalArticle

Yao, S, Zirpoli, G, Bovbjerg, DH, Jandorf, L, Hong, CC, Zhao, H, Sucheston, LE, Tang, L, Roberts, M, Ciupak, G, Davis, W, Hwang, H, Johnson, CS, Trump, DL, McCann, SE, Ademuyiwa, F, Pawlish, KS, Bandera, EV & Ambrosone, CB 2012, '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', Breast Cancer Research, vol. 14, no. 2, R58. https://doi.org/10.1186/bcr3162
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. In: Breast Cancer Research. 2012 ; Vol. 14, No. 2.
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abstract = "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.",
author = "Song Yao and Gary Zirpoli and Bovbjerg, {Dana H.} and Lina Jandorf and Hong, {Chi Chen} and Hua Zhao and Sucheston, {Lara E.} and Li Tang and Michelle Roberts and Gregory Ciupak and Warren Davis and Helena Hwang and Johnson, {Candace S.} and Trump, {Donald L.} and McCann, {Susan E.} and Foluso Ademuyiwa and Pawlish, {Karen S.} and Bandera, {Elisa V.} and Ambrosone, {Christine B.}",
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TY - JOUR

T1 - Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women

T2 - A case-control study

AU - Yao, Song

AU - Zirpoli, Gary

AU - Bovbjerg, Dana H.

AU - Jandorf, Lina

AU - Hong, Chi Chen

AU - Zhao, Hua

AU - Sucheston, Lara E.

AU - Tang, Li

AU - Roberts, Michelle

AU - Ciupak, Gregory

AU - Davis, Warren

AU - Hwang, Helena

AU - Johnson, Candace S.

AU - Trump, Donald L.

AU - McCann, Susan E.

AU - Ademuyiwa, Foluso

AU - Pawlish, Karen S.

AU - Bandera, Elisa V.

AU - Ambrosone, Christine B.

PY - 2012/4/4

Y1 - 2012/4/4

N2 - 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.

AB - 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.

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U2 - 10.1186/bcr3162

DO - 10.1186/bcr3162

M3 - Article

VL - 14

JO - Breast Cancer Research

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