Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity
Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity
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DOI：
10.1016/j.radonc.2012.10.017
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发表时间：
2012-12-01
影响因子：
5.7
通讯作者：
Bentzen, Soren M.
中科院分区：
文献类型：
--
作者：
Barnett, Gillian C.;Elliott, Rebecca M.;Bentzen, Soren M.
背景和目的：据报道，辐射引起的正常组织损伤风险与编码促纤维化细胞因子转化生长因子-β 1 (TGF-β 1) 的 TGFB1 中的单核苷酸多态性 (SNP) 之间的关联仍存在争议。为了克服发表偏倚，国际放射基因组学联盟收集并分析了已发表和未发表研究中的个体患者水平数据。材料和方法：TGFB1 SNP rs1800469 c.-1347T>C（以前称为 C-509T）基因型、治疗相关数据和临床评估的纤维化（治疗后至少 2 年测量）可在 2782 名参与者中获得 来自 11 个队列。所有患者均接受辅助乳房放疗。评估了 STAT（标准化总平均毒性）评分报告的晚期纤维化或总体毒性与 rs1800469 基因型之间的关联。结果：通过单变量或多变量回归分析，未观察到纤维化或总体毒性与 rs1800469 基因型之间存在统计学上显着的关联。从荟萃分析中获得的多变量比值比 (OR) 表明，每增加一个 rs1800469 罕见等位基因，晚期纤维化等级就会增加，为 0.98（95% 置信区间 (CI) 0.85-1.11）。该置信区间足够窄，足以排除携带者与非携带者之间毒性风险的任何临床相关影响。结论：该荟萃分析尚未证实之前的报告。乳腺癌患者纤维化或总体毒性与 rs1800469 基因型之间的关联。它展示了放射基因组学联盟内部的成功合作。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。放射治疗和肿瘤学105（2012）289-295
Background and purpose: Reported associations between risk of radiation-induced normal tissue injury and single nucleotide polymorphisms (SNPs) in TGFB1, encoding the pro-fibrotic cytokine transforming growth factor-beta 1 (TGF-beta 1), remain controversial. To overcome publication bias, the international Radiogenomics Consortium collected and analysed individual patient level data from both published and unpublished studies.Materials and methods: TGFB1 SNP rs1800469 c.-1347T>C (previously known as C-509T) genotype, treatment-related data, and clinically-assessed fibrosis (measured at least 2 years after therapy) were available in 2782 participants from 11 cohorts. All received adjuvant breast radiotherapy. Associations between late fibrosis or overall toxicity, reported by STAT (Standardised Total Average Toxicity) score, and rs1800469 genotype were assessed.Results: No statistically significant associations between either fibrosis or overall toxicity and rs1800469 genotype were observed with univariate or multivariate regression analysis. The multivariate odds ratio (OR), obtained from meta-analysis, for an increase in late fibrosis grade with each additional rare allele of rs1800469 was 0.98 (95% Confidence Interval (CI) 0.85-1.11). This CI is sufficiently narrow to rule out any clinically relevant effect on toxicity risk in carriers vs. non-carriers with a high probability.Conclusion: This meta-analysis has not confirmed previous reports. of association between fibrosis or overall toxicity and rs1800469 genotype in breast cancer patients. It has demonstrated successful collaboration within the Radiogenomics Consortium. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 289-295