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首页> 外文期刊>Carcinogenesis >The role of microrna-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes
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The role of microrna-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes

机译：DNA修复基因中微小RNA结合位点多态性作为膀胱癌和乳腺癌危险因素的作用及其对放疗结果的影响

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MicroRNAs (miRNAs) are involved in post-transcriptional regulation of gene expression through binding to messenger RNAs (mRNA) thereby promoting mRNA degradation or altered translation. A single-nucleotide polymorphism (SNP) located within a miRNA-binding site could thus alter mRNA translation and influence cancer risk and treatment response. The common SNPs located within the 3'-untranslated regions of 20 DNA repair genes were analysed for putative miRNA-binding sites using bioinformatics algorithms, calculating the difference in Gibbs free binding energy (ΔΔG) for each wild-type versus variant allele. Seven SNPs were selected to be genotyped in germ line DNAs both from a bladder cancer case-control series (752 cases and 704 controls) and 202 muscle-invasive bladder cancer radiotherapy cases. The PARP-1 SNP rs8679 was also genotyped in a breast cancer case-control series (257 cases and 512 controls). Without adjustment for multiple testing, multivariate analysis demonstrated an association with increased bladder cancer risk with PARP1 rs8679 (P trend = 0.05) while variant homozygotes of PARP1 rs8679 were also noted to have an increased breast cancer risk (P = 0.03). In the radiotherapy cases, carriers of the RAD51 rs7180135 minor allele had improved cancer-specific survival (hazard ratio 0.52, 95% confidence interval 0.31-0.87, P = 0.01). This is the first report of associations between DNA repair gene miRNA-binding site SNPs with bladder and breast cancer risk and radiotherapy outcomes. If validated, these findings may give further insight into the biology of bladder carcinogenesis, allow testing of the RAD51 SNP as a potential predictive biomarker and also reveal potential targets for new cancer treatments.
机译：MicroRNA（miRNA）通过与信使RNA（mRNA）结合而参与基因表达的转录后调控，从而促进mRNA降解或改变的翻译。因此，位于miRNA结合位点的单核苷酸多态性（SNP）可能会改变mRNA的翻译并影响癌症的风险和治疗反应。使用生物信息学算法分析位于20个DNA修复基因3'-非翻译区内的常见SNPs的miRNA结合位点，计算每种野生型与变异等位基因的吉布斯自由结合能（ΔΔG）的差异。从膀胱癌病例对照系列（752例和704个对照）和202例肌肉浸润性膀胱癌放疗病例中选择了7个SNP用于生殖系DNA的基因分型。在乳腺癌病例对照系列（257例和512对照）中也对PARP-1 SNP rs8679进行了基因分型。如果不进行多重测试调整，多变量分析表明PARP1 rs8679与膀胱癌风险增加相关（P趋势= 0.05），而PARP1 rs8679的纯合体纯合子也有增加乳腺癌风险（P = 0.03）。在放疗情况下，RAD51 rs7180135次要等位基因的携带者具有改善的癌症特异性生存率（危险比0.52，95％置信区间0.31-0.87，P = 0.01）。这是DNA修复基因miRNA结合位点SNP与膀胱癌和乳腺癌风险以及放疗结果之间相关性的首次报道。如果得到验证，则这些发现可能会提供对膀胱癌发生生物学的进一步了解，可以测试RAD51 SNP作为潜在的预测生物标志物，还可以揭示新的癌症治疗方法的潜在靶标。

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