No Association between TGFB1 Polymorphisms and Late Radiotherapy Toxicity: A Meta-Analysis

Mei-Ling Zhu,Pan Xi,Ting-Yan Shi,Mengyun Wang,Leizhen Zheng,Qing-Yi Wei,Kai-Qin Xia,Qiao-Xin Li

doi:10.1371/journal.pone.0076964

Abstract

BackgroundTransforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial.MethodsWe searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue.ResultsWe finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size.ConclusionsThis meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study.

Highlights

Radiotherapy remains a cornerstone of modern cancer management, with curative or palliative potential in roughly half of incident solid tumors, and has the advantage of organ and function preservation in most cases [1]
There is a growing consensus that the risk of normal tissue complication is influenced by single nucleotide polymorphisms (SNPs), the most common genetic variations, which could contribute to patient susceptibility to adverse radiotherapy effects [3]
The -509T>C SNP in the promoter was found to be significantly associated with an increased circulating concentration of TGF-β1 [8], whereas the Arg25Pro SNP in the exon 1 was reported to be associated with inter-individual variation in levels of the TGF-β1 production in vitro and with fibrosis in lung allografts [5]

Summary

Introduction

Radiotherapy remains a cornerstone of modern cancer management, with curative or palliative potential in roughly half of incident solid tumors, and has the advantage of organ and function preservation in most cases [1]. The TGF-β1 protein may contribute to the development of fibrosis, extracellular signaling, inducing apoptosis and inhibiting proliferation in response to radiation-induced DNA damage [1]. Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial. Conclusions: This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study

Methods

Results

Discussion

Conclusion