Schack Line M H, Petersen Stine E, Nielsen Steffen, Lundby Lilly, Høyer Morten, Bentzen Lise, Overgaard Jens, Andreassen Christian N, Alsner Jan
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark.
b Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
Acta Oncol. 2017 Nov;56(11):1514-1521. doi: 10.1080/0284186X.2017.1348626. Epub 2017 Aug 26.
Normal tissue morbidity sets the dose limit for radiotherapy (RT) in cancer treatment and has importance for quality of life for cancer survivors. A previous study of prostate cancer patients treated with RT generated clinical data for radiation-induced morbidity measured by anorectal physiological methods and validated questionnaires. Other studies have identified genetic predictors associated with late radiation-induced morbidity outcome. We have expanded biobank material aiming to validate single nucleotide polymorphisms (SNPs) and a gene expression classifier with endpoints on patient-reported outcomes and biomechanical properties of the anorectum from our cohort matching originally published endpoints.
The present cohort of prostate cancer patients was treated with RT curative intent in 1999-2007. Nine SNPs associated with late radiation-induced morbidity were tested in 96 patients (rs2788612, rs1800629, rs264663, rs2682585, rs2268363, rs1801516, rs13035033, rs7120482 and rs17779457). A validated gene expression profile predictive of resistance to radiation-induced skin fibrosis was tested in 42 patients. An RT-induced anorectal dysfunction score (RT-ARD) served as a fibrosis-surrogate and a measure of overall radiation-induced morbidity.
The lowest p-value found in the genotype analyses was for SNP rs2682585 minor allele (A) in the FSHR gene and the RT-ARD score with odds ratios (OR) = 1.76; 95% CI (0.98-3.17) p = .06, which was out of concordance with original data showing a protective effect of the minor allele. The gene expression profile in patients classified as fibrosis-resistant was associated with high RT-ARD scores OR 4.18; 95% CI (1.1-16.6), p = .04 conflicting with the hypothesis that fibrosis-resistant patients would experience lower RT-ARD scores.
We aimed to validate nine SNPs and a gene expression classifier in a cohort of prostate cancer patients with unique scoring of radiation-induced morbidity. One significant association was found, pointing to the opposite direction of originally published data. We conclude that the material was not able to validate previously published genetic predictors of radiation-induced morbidity.
正常组织的发病率设定了癌症治疗中放射治疗（RT）的剂量限制，并且对癌症幸存者的生活质量具有重要意义。先前一项针对接受RT治疗的前列腺癌患者的研究产生了通过肛肠生理方法和经过验证的问卷测量的放射性发病率的临床数据。其他研究已经确定了与晚期放射性发病率结果相关的基因预测因子。我们扩展了生物样本库材料，旨在验证单核苷酸多态性（SNP）和基因表达分类器，其终点是根据我们队列中患者报告的结果以及与最初发表的终点相匹配的肛肠生物力学特性。
本队列的前列腺癌患者于1999年至2007年接受了根治性RT治疗。在96名患者中测试了9个与晚期放射性发病率相关的SNP（rs2788612、rs1800629、rs264663、rs2682585、rs2268363、rs1801516、rs13035033、rs7120482和rs17779457）。在42名患者中测试了一种经过验证的预测对放射性皮肤纤维化抗性的基因表达谱。RT诱导的肛肠功能障碍评分（RT-ARD）用作纤维化替代指标和总体放射性发病率的衡量指标。
在基因型分析中发现的最低p值是FSHR基因中SNP rs2682585的次要等位基因（A）与RT-ARD评分，优势比（OR）=1.76；95%置信区间（0.98 - 3.17），p = 0.06，这与原始数据显示次要等位基因具有保护作用不一致。被归类为抗纤维化的患者的基因表达谱与高RT-ARD评分相关，OR为4.18；95%置信区间（1.1 - 16.6），p = 0.04，这与抗纤维化患者的RT-ARD评分较低的假设相矛盾。
我们旨在验证一组前列腺癌患者中的9个SNP和一个基因表达分类器，这些患者对放射性发病率有独特的评分。发现了一个显著关联，但指向与最初发表的数据相反的方向。我们得出结论，该材料无法验证先前发表的放射性发病率的基因预测因子。
