Zhai Xiao-Ming, Hu Qun-Chao, Gu Ke, Wang Jian-Ping, Zhang Jun-Ning, Wu Yi-Wei
Department of Radiation Oncology, The first Affiliated Hospital of Soochow University, Suzhou, China.
School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
Asia Pac J Clin Oncol. 2016 Mar;12(1):e125-32. doi: 10.1111/ajco.12117. Epub 2013 Aug 5.
Little is known about the relationship between XRCC1 Codon399 polymorphisms and radiotherapy (RT) outcomes in patients with nasopharyngeal carcinoma (NPC). We aimed to investigate whether XRCC1 Codon399 polymorphisms were correlated to treatment efficacy and normal tissue toxicity in Chinese patients with locally advanced NPC after RT.
Sixty eligible patients with NPC stage III-IVa were recruited. Patients received definitive RT, 66-76 Gy. One cycle neoadjuvant chemotherapy with docetaxel and cisplatin regimen was used before RT, two or three cycles for concurrent chemo-RT followed by two to four cycles adjuvant chemotherapy with the same regimen. Before the treatment, XRCC1 Codon399 polymorphisms were determined by polymerase chain reaction based ligase detection reaction methods.
Six of 60 NPC patients were homozygous for XRCC1 Codon399 Gln/Gln and 35% were heterozygous. The expressions of genotypes were unrelated to gender, age, clinical stage, T stage or N stage. Codon399 Gln/Gln allele correlated with a higher medium-term tumor regression ratio after RT for primary nasopharyngeal neoplasm and metastatic lymph nodes (>80% vs 40-60%, P < 0.01). Compared with other two genotypes, patients with XRCC1 Codon399 Gln/Gln allele were more likely to obtain complete remission of tumor (100% vs 76 and 67%, P > 0.05). No correlation between XRCC1 Codon399 polymorphisms and acute or late radiation-induced injury of normal tissues was observed.
The XRCC1 Codon399 Gln/Gln allele may be associated with better tumor regression, and is suggested as a promising predictive factor for outcome for locally advanced NPC. Further study with larger samples and long-time follow-up is needed for accurate assessment.
关于鼻咽癌（NPC）患者XRCC1密码子399多态性与放疗（RT）疗效之间的关系，目前所知甚少。我们旨在研究XRCC1密码子399多态性是否与中国局部晚期NPC患者放疗后的治疗效果及正常组织毒性相关。
招募了60例符合条件的III-IVa期NPC患者。患者接受根治性放疗，剂量为66-76 Gy。放疗前采用多西他赛和顺铂方案进行1周期新辅助化疗，同步放化疗采用2或3周期相同方案，随后进行2至4周期辅助化疗。治疗前，采用基于聚合酶链反应的连接酶检测反应方法确定XRCC1密码子399多态性。
60例NPC患者中，6例为XRCC1密码子399 Gln/Gln纯合子，35%为杂合子。基因型表达与性别、年龄、临床分期、T分期或N分期无关。密码子399 Gln/Gln等位基因与放疗后鼻咽原发肿瘤和转移淋巴结的中期肿瘤退缩率较高相关（>80%对40-60%，P<0.01）。与其他两种基因型相比，携带XRCC1密码子399 Gln/Gln等位基因的患者更有可能获得肿瘤完全缓解（100%对76%和67%，P>0.05）。未观察到XRCC1密码子399多态性与正常组织急性或晚期放射性损伤之间的相关性。
XRCC1密码子399 Gln/Gln等位基因可能与更好的肿瘤退缩相关，被认为是局部晚期NPC预后的一个有前景的预测因素。需要进一步进行大样本和长期随访研究以进行准确评估。
