Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Radiat Res. 2010 Apr;173(4):505-11. doi: 10.1667/RR1769.1.
Genetic predictive biomarkers of radiosensitivity are being sought to individualize radiation treatment of cancer patients. In this pilot case-control study, we tested the association between TGFB1 T869C codon 10 Leu/Pro (rs1982073), XRCC1 G28152A codon 399 Arg/Gln (rs25487), and XRCC3 C18067T codon 241 Thr/Met (rs861539) single-nucleotide polymorphisms (SNPs) and late reaction to radiotherapy in 60 nasopharyngeal cancer patients. Subcutaneous and deep tissue fibrosis was scored using the RTOG/EORTC grading system. Patients with moderate to severe fibrosis (radiosensitive cases, G2-3, n = 30) were matched and compared to those with little or no reaction (controls, G0-1, n = 30). The three nonsynonymous SNPs were genotyped by direct DNA sequencing. Significant association was observed for TGFB1 T869C and XRCC1 G28152A genotypes (P < or = 0.05). Both variant alleles, TGFB1 869C and XRCC1 28152A, were associated with a lower grade of fibrosis (odds ratios were 0.41, 95% CI: 0.20-0.86, P = 0.02 and 0.30, 95% CI: 0.10-0.89, P = 0.02, respectively), and therefore the wild-types were the risk alleles. Interestingly, there was a significant difference in the median number of risk alleles between the radiosensitive and the control groups (P = 0.006). We conclude that radiotherapy complications are associated with genetic variations in our nasopharynx cancer patients. Our findings support the assumption of the combined effects of multiple SNPs. Large-scale studies are required to confirm these findings before polymorphisms can be used as predictive markers to individualize radiation therapy on genetic bases.
正在寻找放射敏感性的遗传预测生物标志物，以实现癌症患者放射治疗的个体化。在这项初步的病例对照研究中，我们测试了 TGFB1 T869C 密码子 10 亮氨酸/脯氨酸（rs1982073）、XRCC1 G28152A 密码子 399 精氨酸/谷氨酰胺（rs25487）和 XRCC3 C18067T 密码子 241 苏氨酸/蛋氨酸（rs861539）单核苷酸多态性（SNP）与 60 例鼻咽癌患者放射治疗后迟发性反应之间的相关性。采用 RTOG/EORTC 分级系统对皮下组织和深部组织纤维化进行评分。将中重度纤维化患者（放射敏感病例，G2-3，n=30）与反应轻微或无反应患者（对照组，G0-1，n=30）进行匹配和比较。采用直接 DNA 测序法对 3 个非同义 SNP 进行基因分型。TGFB1 T869C 和 XRCC1 G28152A 基因型与纤维化程度较低显著相关（P≤0.05）。两种变异等位基因 TGFB1 869C 和 XRCC1 28152A 均与较低的纤维化程度相关（比值比分别为 0.41，95%CI：0.20-0.86，P=0.02 和 0.30，95%CI：0.10-0.89，P=0.02），因此野生型为风险等位基因。有趣的是，在放射敏感组和对照组之间，风险等位基因的中位数存在显著差异（P=0.006）。我们得出结论，放射治疗并发症与我们鼻咽癌患者的遗传变异有关。我们的发现支持多个 SNP 联合作用的假设。需要进行大规模研究以证实这些发现，然后才能将多态性用作基于遗传的个体化放射治疗的预测标志物。
