Dataset Information

Single-nucleotide polymorphisms of TGF?1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China.

ABSTRACT: BACKGROUND:We examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-?1 (TGF?1) gene and the rs189037 and rs373759 SNPs of the ataxia telangiectasia mutated (ATM) gene on the risk of radiation-induced pneumonitis (RP) in patients who underwent radiotherapy for various thoracic malignancies. METHODS:We determined the genotype and allele distributions of rs1800469 (C-509T), rs1800470 (C869T), rs189037 (A-111G), and rs373759 (126713 G>A) in 141 Han Chinese patients who underwent definitive thoracic radiotherapy (50 to 77 Gy, 5 days/wk) for lung cancer (small cell or non-small cell tumors, n = 97), esophageal squamous cell carcinoma (ESCC, n = 27), or mediastinal cancer (n = 17). Clinical variables were evaluated using multivariate logistic regression models to calculate the relative risk of RP associated with the clinical variables, and a Pearson correlation analysis was used to evaluate the relationship between the SNP genotypes and alleles and the incidence of RP for the various risk factors. RESULTS:The T alleles of rs1800470 (CT/TT) and rs1800469 (CT/TT) and the G allele of rs189037 (GA/GG) were associated with the risk of ? grade-2 RP in the ESCC patients (P = 0.0006, P = 0.0127, and P = 0.0412, respectively), and that the A alleles of rs189037 (AG/AA) and rs373759 (AG/AA) were associated with the risk of ? grade-2 RP in the patients with mediastinal cancer (P = 0.0063 and P = 0.0003, respectively). None of the SNP genotypes were associated with the risk of RP in lung cancer patients. CONCLUSION:The T alleles of the rs1800470 (CT/TT) and rs1800469 (CT/TT) SNPs of TGF?1 and the G allele of the rs189037 (GA/GG) SNP of ATM are independent risk factors for RP in Chinese ESCC patients, and the A alleles of the rs189037 (AG/AA) and rs373759 (AG/AA) SNPs of ATM are independent risk factors for RP in Chinese patients with mediastinal cancer. These SNPs might represent useful biomarkers for personalizing radiotherapy regimens for Chinese patients with ESCC or mediastinal cancer to reduce the incidence of RP. Large-cohort studies of these SNPs in thoracic cancer patients are warranted.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC4659054 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Single-nucleotide polymorphisms of TGFβ1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China.

Xiao Ying Y Yuan Xianglin X Qiu Hong H Li Qianxia Q

International journal of clinical and experimental medicine 20150915 9

<h4>Background</h4>We examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 (TGFβ1) gene and the rs189037 and rs373759 SNPs of the ataxia telangiectasia mutated (ATM) gene on the risk of radiation-induced pneumonitis (RP) in patients who underwent radiotherapy for various thoracic malignancies.<h4>Methods</h4>We determined the genotype and allele distributions of rs1800469 (C-509T), rs1800470 (C869T), rs189037 (A-111G), an ...[more]

PMID: 26629166

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Project description:Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Impaired DNA repair pathways are associated with high sensitivity to radiation exposure. Hence, ATM gene polymorphisms are thought to influence the risk of cancer and radiation-induced pneumonitis (RP) risk in cancer patients treated with radiotherapy. However, the results of previous studies are inconsistent. We therefore conducted this comprehensive meta-analysis.A systematic literature search was performed in the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between the ATM gene polymorphisms and both lung cancer and RP radiotherapy-treated lung cancer (the last search was conducted on Dec.10, 2015). The odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of these relationships. Funnel plots and Begg's and Egger's tests were conducted to assess the publication bias. All analyses were performed in STATA 13.0 software.Ten eligible case-control studies (4731 cases and 5142 controls) on lung cancer susceptibility and four (192 cases and 772 controls) on RP risk were included. The results of the overall and subgroup analyses indicated that in the ATM gene, the rs189037 (-111G?>?A, -4519G?>?A), rs664677 (44831C?>?T, 49238C?>?T) and rs664143 (131,717 T?>?G) polymorphisms were significantly associated with lung cancer susceptibility (OR?=?1.21, 95% CI?=?1.04-1.39, P?=?0.01; OR?=?1.26, 95% CI?=?1.06-1.49, P?=?0.01; OR?=?1.43, 95% CI?=?1.15-1.78, P?<?0.01). Additionally, the rs189037 variant was significantly associated with RP risk (OR?=?1.74, 95% CI?=?1.02-2.97, P?=?0.04). No publication bias was found in the funnel plots, Begg's tests or Egger's tests.The results indicate that the ATM rs189037, rs664677 and rs664143 gene polymorphisms are risk factors for lung cancer, while the ATM rs189037 variant was significantly associated with RP risk.

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.

Dataset Information

Single-nucleotide polymorphisms of TGF?1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China.

Publications

Single-nucleotide polymorphisms of TGFβ1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China.

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