Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany.
J Surg Res. 2010 Nov;164(1):e61-6. doi: 10.1016/j.jss.2010.08.002. Epub 2010 Sep 16.
Neoadjuvant treatment strategies have been developed to improve survival of patients with locally advanced rectal cancer. Since mainly patients with major histopathologic response benefit from this therapy, predictive markers are needed. The gene polymorphism of the X-ray-repair-cross complementing (XRCC1-) gene (rs25487) was analyzed to predict response to neoadjuvant radiochemotherapy and prognosis in patients with locally advanced rectal cancer.
81 patients (51 male; 30 female; median age 59 years) with locally advanced rectal cancer were included in this study. All patients received a neoadjuvant radiochemotherapy (50.4 Gy, 5-FU) followed by surgical therapy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% viable tumor cells (n = 28) and minor response when more than 10% viable tumor cells (n = 53) were detected in the surgical specimen. Genomic DNA was extracted from paraffin-embedded tissues of all study patients. Allelic discrimination was performed by real-time polymerase chain reaction. Two allele-specific TaqMan probes in competition were used for amplification of the XRCC1 gene. Allelic genotyping was correlated with therapy response and prognosis.
Single-nucleotide polymorphism XRCC1 A399G (rs25487) was predictive for therapy response (P = 0.039). Within the AG genotype group, 17 (53%) patients showed a minor response and 15 (47%) patients a major response. In contrast, 39 (78%) of the patients with homogeneous AA or GG genotype were minor responders and only 11 (22%) major responders. No prognostic value was revealed for the XRCC1 A399G (rs25487) gene polymorphism in the multimodality therapy.
Our data supports the role of XRCC1 as a predictive marker for therapy response in the multimodality therapy of patients with locally advanced rectal cancer. Single-nucleotide polymorphism XRCC1 A399G (rs25487) could be applied to individualize treatment strategies.
新辅助治疗策略已被开发出来以提高局部晚期直肠癌患者的生存率。由于主要是有重大组织病理学反应的患者受益于这种治疗，因此需要预测标志物。本研究分析了 X 射线修复交叉互补基因（XRCC1-）基因（rs25487）的基因多态性，以预测局部晚期直肠癌患者对新辅助放化疗的反应和预后。
本研究纳入了 81 例局部晚期直肠癌患者（51 例男性；30 例女性；中位年龄 59 岁）。所有患者均接受新辅助放化疗（50.4Gy，5-FU），随后进行手术治疗。当在手术标本中检测到少于 10%的存活肿瘤细胞时，将组织形态学消退定义为主要反应（n=28），当在手术标本中检测到超过 10%的存活肿瘤细胞时，将其定义为次要反应（n=53）。从所有研究患者的石蜡包埋组织中提取基因组 DNA。通过实时聚合酶链反应进行等位基因鉴别。使用两个等位基因特异性 TaqMan 探针进行 XRCC1 基因的扩增。等位基因基因分型与治疗反应和预后相关。
单核苷酸多态性 XRCC1 A399G（rs25487）可预测治疗反应（P=0.039）。在 AG 基因型组中，17 例（53%）患者表现为次要反应，15 例（47%）患者表现为主要反应。相比之下，在均为 AA 或 GG 基因型的患者中，39 例（78%）为次要反应，仅 11 例（22%）为主要反应。XRCC1 A399G（rs25487）基因多态性在多模态治疗中对预后没有价值。
我们的数据支持 XRCC1 作为局部晚期直肠癌患者多模态治疗中治疗反应预测标志物的作用。单核苷酸多态性 XRCC1 A399G（rs25487）可用于个体化治疗策略。
