Genetic variants in PI3K/AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy

Cancer Medicine

Yang Tang¹  Bo Liu¹  Jing Li¹  Huanlei Wu¹  Ju Yang¹  Xiao Zhou¹  Mingxiao Yi¹  Qianxia Li¹  Shiying Yu¹ 

[1] Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

关键词: AKT;    lung cancer;    PI3CA;    PI3K;    radiation pneumonitis;    SNP;   

DOI  :  10.1002/cam4.564

来源: Wiley

【 摘 要 】

Abstract

PI3K/AKT pathway plays important roles in inflammatory and fibrotic diseases while its connection to radiation pneumonitis (RP) is unclear. In this study, we explored the associations of genetic variants in PI3K/AKT pathway with RP in lung cancer patients with radiotherapy. Two hundred and sixty one lung cancer patients with radiotherapy were included in this prospective study (NCT02490319) and genotyped by MassArray and Sanger Sequence methods. By multivariate Cox hazard analysis and multiple testing, GA/GG genotype of AKT2: rs33933140 (HR = 0.272, 95% CI: 0.140–0.530, P = 1.3E–4, P_c = 9.1E–4), and the GT/GG genotype of PI3CA: rs9838117 (HR = 0.132, 95% CI: 0.042–0.416, P = 0.001, P_c = 0.006) were found to be strongly associated with a decreased occurrence of RP ≥ grade 3. And patients with the CT/TT genotype of AKT2: rs11880261 had a notably higher incidence of RP ≥ grade 3 (HR = 2.950, 95% CI: 1.380–6.305, P = 0.005, P_c = 0.025). We concluded that the genetic variants of PI3K/AKT pathway were significantly related to RP of grade ≥ 3 and may thus be predictors of severe RP before radiotherapy, if further validated in larger population.

【 授权许可】

CC BY   
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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