Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias: An Analysis of CCTG MA.27

Polly Niravath, Bingshu Chen, Judy Anne W. Chapman, Sandeep K. Agarwal, Robert L. Welschhans, Tim Bongartz, Krishna R Kalari, Lois E. Shepherd, John Bartlett, Kathleen Pritchard, Karen Gelmon, Susan G. Hilsenbeck, Mothaffar F. Rimawi, C. Kent Osborne, Paul E. Goss, James N. Ingle

Research output: Contribution to journalArticle

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Abstract

Background: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. Patients and Methods: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation. We also examined 9 baseline inflammatory cytokines: interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon (IFN)γ, IL-10, IL-12p70, IL-17, IL-23, and chemokine ligand (CCL)-20. Finally, we analyzed the multivariate effects of baseline factors: vitamin D level, previously identified musculoskeletal single nucleotide polymorphisms, age, body mass index, and vitamin D receptor (VDR) Fok-I variant genotype on AIA development. Results: Changes in vitamin D from baseline to 6 months were not significantly different between cases and controls. Elevated inflammatory cytokine levels were not associated with development of AIA. The multivariate model included no clinical factors associated with AIA. However, women with the VDR Fok-I variant genotype were more likely to have a lower IL-1β level (P = .0091) and less likely to develop AIA after 6 months of AI compared with those with the wild type VDR (P < .0001). Conclusion: In this nested case-control correlative study, vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1β level, and less likely to develop AIA.

Original languageEnglish (US)
JournalClinical Breast Cancer
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Aromatase Inhibitors
Calcitriol Receptors
Arthralgia
Vitamin D
Cytokines
Interleukin-1
exemestane
Genotype
Interleukin-23
Interleukin-17
Genome-Wide Association Study
Interleukins
Chemokines
Interleukin-10
Interferons
Single Nucleotide Polymorphism
Case-Control Studies
Interleukin-6
Body Mass Index
Tumor Necrosis Factor-alpha

Keywords

  • Aromatase inhibitor-induced arthralgias
  • IL-1 beta
  • Inflammatory cytokines
  • Vitamin D
  • Vitamin D receptor polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias : An Analysis of CCTG MA.27. / Niravath, Polly; Chen, Bingshu; Chapman, Judy Anne W.; Agarwal, Sandeep K.; Welschhans, Robert L.; Bongartz, Tim; Kalari, Krishna R; Shepherd, Lois E.; Bartlett, John; Pritchard, Kathleen; Gelmon, Karen; Hilsenbeck, Susan G.; Rimawi, Mothaffar F.; Osborne, C. Kent; Goss, Paul E.; Ingle, James N.

In: Clinical Breast Cancer, 01.01.2017.

Research output: Contribution to journalArticle

Niravath, P, Chen, B, Chapman, JAW, Agarwal, SK, Welschhans, RL, Bongartz, T, Kalari, KR, Shepherd, LE, Bartlett, J, Pritchard, K, Gelmon, K, Hilsenbeck, SG, Rimawi, MF, Osborne, CK, Goss, PE & Ingle, JN 2017, 'Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias: An Analysis of CCTG MA.27', Clinical Breast Cancer. https://doi.org/10.1016/j.clbc.2017.10.009
Niravath, Polly ; Chen, Bingshu ; Chapman, Judy Anne W. ; Agarwal, Sandeep K. ; Welschhans, Robert L. ; Bongartz, Tim ; Kalari, Krishna R ; Shepherd, Lois E. ; Bartlett, John ; Pritchard, Kathleen ; Gelmon, Karen ; Hilsenbeck, Susan G. ; Rimawi, Mothaffar F. ; Osborne, C. Kent ; Goss, Paul E. ; Ingle, James N. / Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias : An Analysis of CCTG MA.27. In: Clinical Breast Cancer. 2017.
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abstract = "Background: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. Patients and Methods: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation. We also examined 9 baseline inflammatory cytokines: interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon (IFN)γ, IL-10, IL-12p70, IL-17, IL-23, and chemokine ligand (CCL)-20. Finally, we analyzed the multivariate effects of baseline factors: vitamin D level, previously identified musculoskeletal single nucleotide polymorphisms, age, body mass index, and vitamin D receptor (VDR) Fok-I variant genotype on AIA development. Results: Changes in vitamin D from baseline to 6 months were not significantly different between cases and controls. Elevated inflammatory cytokine levels were not associated with development of AIA. The multivariate model included no clinical factors associated with AIA. However, women with the VDR Fok-I variant genotype were more likely to have a lower IL-1β level (P = .0091) and less likely to develop AIA after 6 months of AI compared with those with the wild type VDR (P < .0001). Conclusion: In this nested case-control correlative study, vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1β level, and less likely to develop AIA.",
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T1 - Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias

T2 - An Analysis of CCTG MA.27

AU - Niravath, Polly

AU - Chen, Bingshu

AU - Chapman, Judy Anne W.

AU - Agarwal, Sandeep K.

AU - Welschhans, Robert L.

AU - Bongartz, Tim

AU - Kalari, Krishna R

AU - Shepherd, Lois E.

AU - Bartlett, John

AU - Pritchard, Kathleen

AU - Gelmon, Karen

AU - Hilsenbeck, Susan G.

AU - Rimawi, Mothaffar F.

AU - Osborne, C. Kent

AU - Goss, Paul E.

AU - Ingle, James N.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. Patients and Methods: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation. We also examined 9 baseline inflammatory cytokines: interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon (IFN)γ, IL-10, IL-12p70, IL-17, IL-23, and chemokine ligand (CCL)-20. Finally, we analyzed the multivariate effects of baseline factors: vitamin D level, previously identified musculoskeletal single nucleotide polymorphisms, age, body mass index, and vitamin D receptor (VDR) Fok-I variant genotype on AIA development. Results: Changes in vitamin D from baseline to 6 months were not significantly different between cases and controls. Elevated inflammatory cytokine levels were not associated with development of AIA. The multivariate model included no clinical factors associated with AIA. However, women with the VDR Fok-I variant genotype were more likely to have a lower IL-1β level (P = .0091) and less likely to develop AIA after 6 months of AI compared with those with the wild type VDR (P < .0001). Conclusion: In this nested case-control correlative study, vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1β level, and less likely to develop AIA.

AB - Background: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. Patients and Methods: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation. We also examined 9 baseline inflammatory cytokines: interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon (IFN)γ, IL-10, IL-12p70, IL-17, IL-23, and chemokine ligand (CCL)-20. Finally, we analyzed the multivariate effects of baseline factors: vitamin D level, previously identified musculoskeletal single nucleotide polymorphisms, age, body mass index, and vitamin D receptor (VDR) Fok-I variant genotype on AIA development. Results: Changes in vitamin D from baseline to 6 months were not significantly different between cases and controls. Elevated inflammatory cytokine levels were not associated with development of AIA. The multivariate model included no clinical factors associated with AIA. However, women with the VDR Fok-I variant genotype were more likely to have a lower IL-1β level (P = .0091) and less likely to develop AIA after 6 months of AI compared with those with the wild type VDR (P < .0001). Conclusion: In this nested case-control correlative study, vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1β level, and less likely to develop AIA.

KW - Aromatase inhibitor-induced arthralgias

KW - IL-1 beta

KW - Inflammatory cytokines

KW - Vitamin D

KW - Vitamin D receptor polymorphisms

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