Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy
Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy
复制标题
HIPK2基因变异对接受放射治疗的肺癌患者发生严重放射性肺炎风险的影响
DOI：
10.1186/s13014-019-1456-0
复制
发表时间：
2020-01-08
影响因子：
3.6
通讯作者：
Yuan, Xiang'Lin
中科院分区：
文献类型：
--
作者：
Tang, Yang;Yang, Li;Yuan, Xiang'Lin
背景
同源结构域相互作用蛋白激酶2（Homeodomain-interacting protein kinase 2，HIPK 2）在细胞凋亡、细胞增殖和DNA损伤修复等多个重要生理过程中发挥着重要作用，近年来受到越来越多的关注。最重要的是，HIPK 2被证明在炎症中起调节作用，并影响成纤维细胞的表型和活性。本研究旨在评估HIPK 2基因变异对肺部恶性肿瘤患者放射性肺炎风险的影响。
方法
采用桑格序列分析法对169例肺癌放疗患者进行基因分型。采用多因素考克斯风险分析和多重检验方法估计可能与放射性肺炎（RP）发生有关的所有因素的风险比（HR）和95%可信区间（CI）。
结果
平均肺剂量（MLD）≥ 15 Gy、肺V20 ≥ 24%的患者发生RP ≥ 2级的风险高于其他患者（HR = 1.888，95%CI：1.186-3.004，P = 0.007; HR = 2.126，95%CI：1.338-3.378，P = 0.001）。重要的是，HIPK 2：rs 2030712的CC基因型与RP ≥ 2级的发生率增加密切相关（HR = 2.146，95%CI：1.215-3.791，P = 0.009）。
结论
HIPK2：rs 2030712与≥ 2级RP的发生有显著相关性，如果在更大的人群中进一步验证，rs 2030712可能是放射治疗前重度RP的重要预测因子之一。
试验注册
我们的研究是前瞻性和观察性的。该研究在ClinicalTrials.gov数据库中注册为NCT 02490319。
Background
Homeodomain-interacting protein kinase 2 (HIPK2) has increasingly drawn attention as recent researches demonstrated its unique role in the regulation of multiple fundamental processes such as apoptosis, proliferation and DNA damage repair. Most importantly, HIPK2 was shown to play regulatory role in inflammation and influence the phenotype and activity of fibroblasts. In this study, we aimed to evaluate the impact of HIPK2 gene variant on risk of radiation pneumonitis for patients with pulmonary malignancies.
Methods
169 lung cancer patients with radiotherapy were included in our prospective study and genotyped by Sanger Sequence method. Multivariable Cox hazard analysis and multiple testing were applied to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of all factors possibly related to the risk of radiation pneumonitis (RP).
Results
Patients with Mean Lung Dose (MLD) ≥ 15Gy, Lung V20 ≥ 24% had higher risk of RP ≥ grade 2 compared with those counterparts (HR = 1.888, 95% CI: 1.186–3.004, P = 0.007; HR = 2.126, 95% CI: 1.338–3.378, P = 0.001, respectively). Importantly, CC genotype of HIPK2: rs2030712 were strongly related to an increased occurrence of RP ≥ grade 2 (HR = 2.146, 95% CI: 1.215–3.791, P = 0.009).
Conclusion
HIPK2: rs2030712 was found to be significantly related to RP of grade ≥ 2 in our cohort, and may thus be one of the important predictors of severe RP before radiotherapy, if further validated in larger population.
Trial registration
Our study was prospective and observational. The research was registered in ClinicalTrials.gov database as NCT02490319.