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A polymorphism in the DNA repair domain of APEX1 is associated with the radiation-induced pneumonitis risk among lung cancer patients after radiotherapy.

ABSTRACT: OBJECTIVE: To examine the association of tag single nucleotide polymorphisms (tagSNPs) (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 with the risk of severe radiation-induced pneumonitis (RP) after radiotherapy among Han Chinese patients with lung cancer. METHODS: A total of 168 patients with lung cancer who were receiving radiotherapy were prospectively recruited. RP was evaluated according to the Radiation Therapy Oncology Group. A case-control study was performed. The case group included patients with RP grade of ?3, while the control group comprised patients with RP grades <3. Four tagSNPs of APEX1 were genotyped in 126 patients with complete follow-up by multi-SNaPshot® (Genesky Biotechnologies Inc., Shanghai, China) genotyping assays. RESULTS were assessed by a logistic regression model for RP risk and Mantal-Cox log-rank test for the cumulative RP probability by the genotypes. RESULTS: rs1130409 was associated with severe RP. GT genotype of rs1130409 was significantly higher in patients with RP than in those of the control group [68.8% vs 41.8%; p = 0.025; resulting odds ratio (OR), 5.98]. Patients with lung cancer bearing the G allele had a 5.83-fold higher risk of RP than those with the wild TT genotype [OR = 5.83; 95% confidence interval (CI), 1.27-26.90; p = 0.024], and this was further confirmed by the binary regression adjusted by some confounding factors, including Karnofsky performance scale, concurrent chemotherapy-radiotherapy and lung volume receiving >30 Gy (OR = 6.96; 95% CI, 1.36-35.77; p = 0.02). rs1130409 was also associated with the time to occurrence of severe RP (p = 0.04). Three-dimensional model APEX1 protein showed that rs1130409 is located in the random coil structure corresponding to the DNA repair function region. ADVANCES IN KNOWLEDGE: rs1130409 of APEX1 can be a predictor of RP grades ?3 among patients with lung cancer.

SUBMITTER: Li H

PROVIDER: S-EPMC4112388 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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A polymorphism in the DNA repair domain of APEX1 is associated with the radiation-induced pneumonitis risk among lung cancer patients after radiotherapy.

Li H H Liu G G Xia L L Zhou Q Q Xiong J J Xian J J Du M M Zhang L L Liao L L Su X X Li Z Z Luo Q Q Cheng Y Y Zhang T T Wang D D Yang Z-Z ZZ

The British journal of radiology 20140602 1040

<h4>Objective</h4>To examine the association of tag single nucleotide polymorphisms (tagSNPs) (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 with the risk of severe radiation-induced pneumonitis (RP) after radiotherapy among Han Chinese patients with lung cancer.<h4>Methods</h4>A total of 168 patients with lung cancer who were receiving radiotherapy were prospectively recruited. RP was evaluated according to the Radiation Therapy Oncology Group. A case-control study was performed. The ...[more]

PMID: 24884729

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Project description:PurposeWhilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.Methods and materialsFrom January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.ResultsWith a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).ConclusionsTreatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.

Project description:Background:Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). Methods:Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ?6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. Results:Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ? grade 2 and ? grade 3 were significantly lower in CAM-era (grade ?2, 16% vs. 9.6%, P=0.047; grade ?3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ? grade 3 was significantly lower, and that of grade ?2 had a lower tendency (grade ?3, 7.2% vs. 0%, P=0.011; grade ?2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ? grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ? grade 2 and ? grade 3. Conclusions:CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be con?rmed in prospective studies.

Dataset Information

A polymorphism in the DNA repair domain of APEX1 is associated with the radiation-induced pneumonitis risk among lung cancer patients after radiotherapy.

Publications

A polymorphism in the DNA repair domain of APEX1 is associated with the radiation-induced pneumonitis risk among lung cancer patients after radiotherapy.

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