Joint effect of urinary total arsenic level and VEGF-A genetic polymorphisms on the recurrence of renal cell carcinoma
Journal
PLoS ONE
Journal Volume
10
Journal Issue
12
Pages
e0145410
Date Issued
2015
Author(s)
Abstract
The results of our previous study suggested that high urinary total arsenic levels were associated with an increased risk of renal cell carcinoma (RCC). Germline genetic polymorphisms might also affect cancer risk and clinical outcomes. Vascular endothelial growth factor (VEGF) plays an important role in vasculogenesis and angiogenesis, but the combined effect of these factors on RCC remains unclear. In this study, we explored the association between the VEGFA -2578C>A, -1498T>C, -1154G>A, -634G>C, and +936C>T gene polymorphisms and RCC. We also evaluated the combined effects of the VEGF-A haplotypes and urinary total arsenic levels on the prognosis of RCC. This case-control study was conducted with 191 RCC patients who were diagnosed with renal tumors on the basis of image-guided biopsy or surgical resections. An additional 376 age- And gender-matched controls were recruited. Concentrations of urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotyping was investigated using fluorescent-based TaqMan allelic discrimination. We observed no significant associations between VEGF-A haplotypes and RCC risk. However, the VEGF-A ACGG haplotype from VEGF-A -2578, -1498, -1154, and -634 was significantly associated with an increased recurrence of RCC (OR = 3.34, 95% CI = 1.03-10.91). Urinary total arsenic level was significantly associated with the risk of RCC in a dose-response manner, but it was not related to the recurrence of RCC. The combination of high urinary total arsenic level and VEGF-A risk haplotypes affected the OR of RCC recurrence in a dose-response manner. This is the first study to show that joint effect of high urinary total arsenic and VEGF-A risk haplotypes may influence the risk of RCC recurrence in humans who live in an area without obvious arsenic exposure. ? 2015 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source arecredited.
SDGs
Other Subjects
arsenic; vasculotropin A; arsenic; vasculotropin A; VEGFA protein, human; adult; Article; atomic absorption spectrometry; cancer prognosis; cancer recurrence; case control study; controlled study; disease association; female; fluorescence analysis; gene; genetic polymorphism; genotype; haplotype; high performance liquid chromatography; human; kidney carcinoma; major clinical study; male; risk assessment; urine level; VEGF A gene; genetic association study; genetic predisposition; genetics; image guided biopsy; kidney carcinoma; kidney tumor; pathology; risk factor; tumor recurrence; urine; Arsenic; Carcinoma, Renal Cell; Case-Control Studies; Chromatography, High Pressure Liquid; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Image-Guided Biopsy; Kidney Neoplasms; Male; Neoplasm Recurrence, Local; Polymorphism, Genetic; Risk Factors; Vascular Endothelial Growth Factor A
Publisher
Public Library of Science
Type
journal article