Dataset Information

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors.

ABSTRACT:

Introduction

Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA.

Methods

We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders.

Results

Among 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001).

Conclusions

Functional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA.

SUBMITTER: Mao JJ

PROVIDER: S-EPMC3109575 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors.

Mao Jun J JJ Su H Irene HI Feng Rui R Donelson Michelle L ML Aplenc Richard R Rebbeck Timothy R TR Stanczyk Frank F DeMichele Angela A

Breast cancer research : BCR 20110120 1

<h4>Introduction</h4>Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA.<h4>Methods</h4>We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving ...[more]

PMID: 21251330

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Project description:In postmenopausal women diagnosed with breast cancer (BC), most BC tumors are hormone receptor positive and guidelines recommend adjuvant endocrine therapy that includes an aromatase inhibitor (AI). This study investigates the impact of a 6-week, home-based, self-directed walking program on the commonly reported side effect of AI-associated arthralgia (AIAA).In this phase II trial, consented BC patients were randomized to walking Intervention (n?=?31) or Wait List Control (WLC; n?=?31). Eligibility criteria included: stage 0-III BC, on AI for at least 4 weeks, ?3 on a 5-point scale inquiring about joint symptom intensity "at its worst," and exercising ?150 minutes per week. Outcomes were self-reported joint symptoms and psychosocial measures. Analyses comparing Intervention and WLC groups were conducted on an intention-to-treat basis to assess intervention impact at 6 weeks (postintervention) and at 6-months follow-up. Adjusted means were calculated to assess differences in two groups.In our final sample (n?=?62), mean age was 64 years, 74% were white, and 63% had a body mass index of 30 or higher. At postintervention, Intervention group participants reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living (ADL), and less perceived helplessness in managing joint symptoms. At 6-months follow-up (postwalking period in both Intervention and WLC), walking minutes per week had decreased significantly; however, improvements in stiffness and difficulty with ADLs were maintained.This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA.Breast cancer survivors whose adjuvant endocrine treatment includes an aromatase inhibitor (AI) often experience the side effect of AI-associated arthralgia (AIAA). This study investigates the impact of a 6-week, home-based, self-directed walking program in the management of AIAA. Compared with Wait List Control, women in the Intervention group reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living, and less perceived helplessness in managing joint symptoms. This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA.

Dataset Information

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors.

Introduction

Methods

Results

Conclusions

Publications

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors.

Similar Datasets

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