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Angiogenesis-associated sequence variants relative to breast cancer recurrence and survival

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Abstract

Introduction

Breast cancer (BrCA) risk stratification using clinico-pathological biomarkers helps improve disease prognosis prediction. However, disease recurrence rates remain unfavorable and individualized clinical management strategies are needed. Consequently, we evaluated the influence of 14 sequence variants detected in IL-10, TGF-β1, VEGF, and their associated receptors as effective predictors of BrCA clinical outcomes.

Methods

Tumor DNA samples collected from 441 BrCA patients were genotyped using TaqMan-PCR. Most selected targets alter cytokine serum/plasma levels or signaling pathways. Relationships between genetic profiles and recurrence as well as disease-related mortality were evaluated using cumulative incidence curves and competing risk regression models.

Results

The VEGF −2578C allele was associated with a 1.3- to 1.6-fold increase in BrCA recurrence (HRtrend = 1.28; 95% CI = 0.96–1.72) and disease-related mortality (HRtrend = 1.56; 95% CI = 0.93–2.56). Although this marker was marginally significant relative to BrCA outcomes, there were substantial gains in the 5- and 8-year predictive accuracy compared to standard prognostic indicators. Among ER+/PR+ status patients, there was a significant impact of the VEGF −2578CC genotype on disease recurrence and predictive accuracy.

Conclusions

Our findings suggest inheritance of the VEGF −2578C allele could serve as an independent prognostic indicator of BrCA prognosis. The VEGF −2578 marker may have clinical implications among a subset of ER+/PR+ patients with an aggressive phenotype. Because the VEGF −2578C allele is linked to high VEGF expression, this cytokine is a potential prognostic and targeted clinical management tool.

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Acknowledgments

Special thanks are extended to Andrew Marsh for editing services. The authors appreciate access to the CGeMM DNA Core Facility at the UofL, directed by Dr. Ron Gregg, for the use of their high-throughput genotyping facilities. Grant Support: This project was supported in part by a JGBCC Pilot Project Initiative Grant, a Prostate Cancer Foundation Award, and the JGBCC Bucks for Brains “Our Highest Potential” in Cancer Research Endowment to LRK and the Phi Beta Psi Charity Trust to JLW. GNB was partially supported by the National Institute of Health grants P30-ES014443 and P20-RR/DE177702, and DOE grant 10EM00542.

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Correspondence to LaCreis R. Kidd.

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LaCreis R. Kidd and Guy N. Brock contributed equally to this work.

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Kidd, L.R., Brock, G.N., VanCleave, T.T. et al. Angiogenesis-associated sequence variants relative to breast cancer recurrence and survival. Cancer Causes Control 21, 1545–1557 (2010). https://doi.org/10.1007/s10552-010-9583-9

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  • DOI: https://doi.org/10.1007/s10552-010-9583-9

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