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Clin Breast Cancer. 2018 Feb;18(1):78-87. doi: 10.1016/j.clbc.2017.10.009. Epub 2017 Oct 16.

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

Author information

1
Department of Internal Medicine, Baylor College of Medicine, Houston, TX. Electronic address: paniravath@houstonmethodist.org.
2
Department of Internal Medicine, Queens University Cancer Research Institute, Queen's Cancer Research Institute, Kingston, Ontario, Canada.
3
Department of Internal Medicine, Baylor College of Medicine, Houston, TX.
4
Department of Internal Medicine, Vanderbilt University, Nashville, TN.
5
Department of Internal Medicine, Mayo Clinic, Rochester, MN.
6
Department of Internal Medicine, Queens University Cancer Research Institute, Kingston, Ontario, Canada.
7
Department of Internal Medicine, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
8
Department of Internal Medicine, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
9
Department of Internal Medicine, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
10
Department of Internal Medicine, Harvard Medical School, Boston, MA.

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.

KEYWORDS:

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

PMID:
29128193
DOI:
10.1016/j.clbc.2017.10.009
[Indexed for MEDLINE]

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