Open AccessGenetic variants in PI 3K/ AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy
Author(s) -
Tang Yang,
Liu Bo,
Li Jing,
Wu Huanlei,
Yang Ju,
Zhou Xiao,
Yi Mingxiao,
Li Qianxia,
Yu Shiying,
Yuan Xianglin
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.564
Subject(s) - lung cancer , genotype , medicine , protein kinase b , radiation therapy , hazard ratio , pneumonitis , gastroenterology , proportional hazards model , oncology , cancer , population , radiation pneumonitis , lung , biology , apoptosis , genetics , gene , confidence interval , environmental health
PI 3K/ 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 PI 3K/ 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 ( NCT 02490319) and genotyped by MassArray and Sanger Sequence methods. By multivariate Cox hazard analysis and multiple testing, GA / GG genotype of AKT 2 : 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 PI 3 CA : 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 AKT 2 : 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 PI 3K/ 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.