Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radi
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RESEARCH
Open Access
Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy Yang Tang1†, Li Yang2†, Wan Qin1, Min’ Xiao Yi1, Bo Liu1 and Xiang’Lin Yuan1*
Abstract 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. Keywords: Radiation pneumonitis, Lung cancer, HIPK2, SNP
Background Globally, lung cancer currently remains as the top one cause of cancer-related mortality. According to the latest statistical report, there are 2.1 million new lung cancer cases and 1.8 million deaths predicted globally in 2018, nearly close to 1 in 5 (18.4%) of all cancer deaths [1]. Among all countries worldwide, China suffered from high rates of male lung cancer (above 40 per 100,000) in 2018. Radiotherapy (RT), with or without chemotherapy, * Correspondence: [email protected] † Yang Tang and Li Yang contributed equally to this work. 1 Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China Full list of author information is available at the end of the article
still acts as the fundamental treatment for lung cancer patients. However, the efficacy of radiotherapy is restrained due to a series of RT-related complications that cause patients intolerance. Radiation pneumonitis (RP) is a type of inflammation and subsequent fibrosis that occurs after irradiation, which is the most common complication and the major dose-limiting toxicity associat
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