评估保乳手术联合全乳放疗（BCS + RT）治疗的乳腺癌患者中 p53 结合蛋白 1（TP53BP1）基因的单核苷酸多态性（SNPs）。
Evaluation of single nucleotide polymorphisms (SNPs) in the p53 binding protein 1 (TP53BP1) gene in breast cancer patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT).
机构信息
Robert Wood Johnson Medical School-Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA.
出版信息
Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):385-91. doi: 10.1016/j.ijrobp.2010.02.005. Epub 2010 Jun 18.
PURPOSE
TP53BP1 is a key component of radiation-induced deoxyribonucleic acid damage repair. The purpose of this study was to evaluate the significance of a known common single nucleotide polymorphism in this gene (rs560191) in patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT).
METHODS AND MATERIALS
The population consisted of 176 premenopausal women treated with BCS + RT (median follow-up, 12 years). Genomic deoxyribonucleic acid was processed by use of TaqMan assays. Each allele for rs560191 was either C or G, so each patient was therefore classified as CC, CG, or GG. Patients were grouped as GG if they were homozygous for the variant G allele or CC-CG if they carried at least one copy of the common C allele (CC or CG).
RESULTS
Of the 176 women, 124 (71%) were CC-CG and 52 (29%) were GG. The mean age was 44 years for GG vs. 38 years for CC-CG (p < 0.001). GG was more common in African-American women than white women (69% vs. 13%, p < 0.001) and more commonly estrogen receptor negative (70% vs. 49%, p = 0.02). There were no significant correlations of rs560191 with other critical variables. Despite the fact that GG patients were older, the 10-year rate of local relapses was higher (22% for GG vs. 12% for CC-CG, p = 0.04).
CONCLUSIONS
This novel avenue of investigation of polymorphisms in radiation repair/response genes in patients treated with BCS + RT suggests a correlation to local relapse. Additional evaluation is needed to assess the biological and functional significance of these single nucleotide polymorphisms, and larger confirmatory validation studies will be required to determine the clinical implications.
目的
TP53BP1 是辐射诱导脱氧核糖核酸损伤修复的关键组成部分。本研究旨在评估该基因（rs560191）中已知常见单核苷酸多态性在接受保乳手术和全乳放疗（BCS + RT）治疗的患者中的意义。
方法和材料
该人群由 176 例接受 BCS + RT 治疗的绝经前妇女组成（中位随访时间为 12 年）。使用 TaqMan 检测法处理基因组脱氧核糖核酸。rs560191 的每个等位基因要么是 C 要么是 G，因此每个患者被分为 CC、CG 或 GG。如果患者携带变异 G 等位基因的纯合子，则将其归为 GG，如果携带至少一个常见 C 等位基因（CC 或 CG）的副本，则将其归为 CC-CG。
结果
在 176 名女性中，124 名（71%）为 CC-CG，52 名（29%）为 GG。GG 的平均年龄为 44 岁，而 CC-CG 的平均年龄为 38 岁（p < 0.001）。GG 在非裔美国女性中比白人女性更为常见（69%比 13%，p < 0.001），并且更常见雌激素受体阴性（70%比 49%，p = 0.02）。rs560191 与其他关键变量之间没有明显的相关性。尽管 GG 患者年龄较大，但 10 年局部复发率较高（22%对 CC-CG，p = 0.04）。
结论
本研究对接受 BCS + RT 治疗的患者中辐射修复/反应基因的多态性进行了新的研究，提示与局部复发相关。需要进一步评估这些单核苷酸多态性的生物学和功能意义，并且需要更大的验证性验证研究来确定其临床意义。
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