p53基因codon 72多态性与乳腺癌术后放化疗疗效相关性分析

目的:分析p53基因codon 72多态性与乳腺癌患者术后放化疗的预后相关性。方法:选取北京大学肿瘤医院乳腺癌患者术后接受放化疗427 例，采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）方法分析其p53基因codon 72多态性，比较不同基因型患者间复发及生存的差异。结果:全部患者基因型分布为Pro/Pro 型18.3%（78/427）、Pro/Arg型44.0%（188/427）、Arg/Arg型37.7%（161/427）。3 种基因型间无局部复发生存（LRFS）、无局部区域复发生存（LRRFS ）、无远处转移生存（DDFS）及总生存（OS）均无显著性差异（均P>0.05）。 427 例患者中雌激素受体（ER）阳性为303 例，其中Arg/Arg基因型患者OS明显优于Pro/Pro 基因型患者（χ2=6.330，P=0.042）。 在多因素分析中p53基因codon 72多态性是ER阳性患者LRFS、LRRFS 、DDFS及OS的独立预后因素，Pro/Pro 基因型的患者较Arg/Arg基因型的局部复发风险增加5.9 倍（HR= 5.9，95%CI 1.1～31.1，P=0.036），局部区域复发风险增加3.1 倍（HR= 3.1，95%CI 1.1～9.1，P=0.039），远处转移风险增加2.8 倍（HR= 2.8，95%CI 1.3～6.0，P=0.010），死亡风险增加4 倍（HR= 4.0，95%CI 1.3～12.0，P=0.013）。 结论:在ER阳性的乳腺癌术后接受放化疗患者中，Pro/Pro 基因型的局部及局部区域复发风险、远处转移风险、死亡风险均高于Arg/Arg基因型。 

Association between p53 codon 72 polymorphism and curative ef-fect of postoperative chemo-radiotherapy for breast cancer

Objective:To investigate the association between p53codon 72polymorphism and the prognosis of breast cancer pa-tients receiving chemotherapy and radiotherapy after surgery. Methods:A total of 427 breast cancer patients treated with chemo-radio-therapy after surgery at Beijing Cancer Hospital were selected for this study. Polymerase chain reaction –restriction fragment length polymorphism was adopted to analyze the p 53codon 72polymorphism. Survival analysis was conducted to compare the disparities of recurrence and survival among the patients with different p53codon 72polymorphic variants. Results: The distribution of three geno-types of p53codon 72in our cohort is as follows: Pro/Pro 18.3% (78/427), Pro/Arg 44.0% (188/427), and Arg/Arg 37.7% (161/427). No significant difference was observed among the local recurrence-free survival (LRFS), loco-regional recurrence-free survival (LR-RFS), distant disease-free survival (DDFS), and overall survival (OS) among the three genotypes (all P> 0.05). Among the 303 estro -gen receptor (ER)-positive patients, OS was significantly better in patients with Arg/Arg genotype than those with Pro/Pro genotype ( χ2=6.33, P=0.042). The multivariate analysis showed that the p 53codon 72polymorphism is an independent factor of prognosis for LRFS, LRRFS, DDFS, and OS of ER-positive patients. For the ER positive patients with Pro/Pro genotype, the local recurrence, local-regional recurrence, distant metastasis, and mortality risks were 5.9 (HR=5.9, 95% CI 1.1-31.1, P=0.036), 3.1 (HR = 3.1, 95% CI1.1-9.1, P=0.039), 2.8 (HR=2.8, 95% CI1.3-6.0, P=0.010), and 4.0 (HR=4.0, 95% CI1.3-12.0, P=0.013) times higher than those with Arg/Arg genotype, respectively. Conclusion:For ER-positive breast cancer patients who underwent surgery and chemo-radiotherapy, the local recurrence, loco-regional recurrence, distant metastasis, and mortality risk with Pro/Pro genotype are significantly higher compared to those with Arg/Arg genotype.