Buchholz T A, Wu X
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):533-7. doi: 10.1016/s0360-3016(00)01502-9.
In in vivo models, radiation-induced genomic instability correlates with the risk of breast cancer development. In addition, homozygous mutations in tumor suppressor genes associated with breast cancer development adversely affects the processing and repair of radiation-induced DNA damage. We performed a case-control study to determine whether an assay measuring radiation-induced chromatid breaks correlated with the risk of having bilateral breast cancer.
Patients were prospectively studied on an institutional review board-approved protocol. We included only women with bilateral breast cancer as cases to obtain patients with a presumed genetic susceptibility for breast cancer. Controls were healthy women without a previous cancer history. A mutagen sensitivity assay using gamma-radiation was performed on lymphocytes obtained from 26 cases and 18 controls. One milliliter of whole blood was cultured with 9 mL of blood medium for 91 h and then treated with 125 cGy using a Cs-137 irradiator. Following an additional 4 h in culture, cells were treated with Colcemid for 1 h to arrest cells in metaphase. The number of chromatid breaks per cell was counted using a minimum of 50 metaphase spreads for each sample.
Cases had a statistically higher number of gamma-radiation-induced chromatid breaks per cell than controls, with mean values of 0.61 +/- 0.24 vs. 0.45 +/- 0.14, respectively (p = 0.034, Wilcoxon rank sum test). Using the 75th percentile value in the control group as a definition of radiation sensitivity, the radiation-sensitive individuals had a 2.83-fold increased odds ratio for breast cancer development compared with individuals who were not radiation sensitive (95% confidence intervals of 0.83 and 9.67).
These preliminary data suggest that sensitivity to radiation-induced chromatid breaks in lymphocytes correlates with the risk of bilateral breast cancer. Although the differences between cases and controls were statistically significant, the small sample size necessitates that this finding be validated in a larger study. More data are also needed to determine whether this sensitivity is limited to breast cancer patients with a genetic susceptibility for the disease or also applies to the general breast cancer population.
在体内模型中，辐射诱导的基因组不稳定性与乳腺癌发生风险相关。此外，与乳腺癌发生相关的肿瘤抑制基因的纯合突变会对辐射诱导的DNA损伤的处理和修复产生不利影响。我们进行了一项病例对照研究，以确定一项测量辐射诱导的染色单体断裂的检测方法是否与双侧乳腺癌的发生风险相关。
患者按照机构审查委员会批准的方案进行前瞻性研究。我们仅将双侧乳腺癌女性作为病例纳入，以获得具有假定乳腺癌遗传易感性的患者。对照为无既往癌症病史的健康女性。对从26例病例和18例对照中获取的淋巴细胞进行了使用γ射线的诱变敏感性检测。将1毫升全血与9毫升血液培养基一起培养91小时，然后使用Cs - 137辐照器用125 cGy进行处理。在额外培养4小时后，用秋水仙酰胺处理细胞1小时以使细胞停滞在中期。每个样本使用至少50个中期分裂相来计数每个细胞的染色单体断裂数。
病例组每个细胞中γ射线诱导的染色单体断裂数在统计学上高于对照组，平均值分别为0.61±0.24和0.45±0.14（p = 0.034，Wilcoxon秩和检验）。以对照组的第75百分位数作为辐射敏感性的定义，与非辐射敏感个体相比，辐射敏感个体患乳腺癌的比值比增加了2.83倍（95%置信区间为0.83和9.67）。
这些初步数据表明，淋巴细胞对辐射诱导的染色单体断裂的敏感性与双侧乳腺癌的发生风险相关。尽管病例组和对照组之间的差异具有统计学意义，但样本量较小使得这一发现需要在更大规模的研究中得到验证。还需要更多数据来确定这种敏感性是否仅限于具有该疾病遗传易感性的乳腺癌患者，还是也适用于一般乳腺癌人群。
