Department of Urology, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Urol Oncol. 2013 Oct;31(7):1231-41. doi: 10.1016/j.urolonc.2011.11.031. Epub 2011 Dec 16.
We have reported previously that the TP53 codon72 polymorphism (rs1042522) is associated with the incidence and invasiveness of bladder cancer in a Han Chinese population. Using an enlarged sample, we investigated the role of rs1042522 and of tagSNPs that were predicted to be in linkage disequilibrium with codon72 in relation to the incidence, invasiveness, and prognosis of bladder cancer.
A sample of 201 patients and 311 controls without cancer were genotyped for 5 tagSNPs using tetra-primer ARMS and/or an allele-specific PCR technique.
The genotyped data were analyzed using Haploview 4.2, and a 10,000-permutation test showed that the rs9895829G allele (P = 0.003) and the rs1788227C allele (P = 0.027) were both associated with the incidence of bladder cancer. With respect to haplotype associations, after the data were adjusted for age, the haplotypes GTT (P = 0.001) and GGTC (P < 0.001) were correlated with a low incidence of bladder cancer. In contrast, none of the TP53 haplotypes were associated significantly with high tumor grade or muscle invasiveness. On the basis of Cox regression analysis, haplotype CGCC and invasiveness were associated with cancer-related death. Structural equation modeling showed that haplotypes GGCC and CGCC played opposing roles with respect to bladder cancer-related death; haplotype GGCC was a protective factor, whereas haplotype CGCC was a risk factor.
The TP53 codon72 polymorphism appears to play a crucial role in determining the association between TP53 haplotype and the incidence and prognosis of bladder cancer. Further functional assays to confirm whether these TP53 haplotypic variants interact with the proteins N-Myc and NDRG is necessary.
我们曾报道过 TP53 密码子 72 多态性（rs1042522）与汉族人群膀胱癌的发生率和侵袭性相关。使用一个更大的样本，我们研究了 rs1042522 以及预测与密码子 72 处于连锁不平衡的标记 SNP 与膀胱癌的发生率、侵袭性和预后的关系。
采用四引物 ARMS 和/或等位基因特异性 PCR 技术，对 201 例膀胱癌患者和 311 例无癌症对照者的 5 个标记 SNP 进行了基因分型。
使用 Haploview 4.2 分析了基因分型数据，10000 次置换检验显示，rs9895829G 等位基因（P=0.003）和 rs1788227C 等位基因（P=0.027）均与膀胱癌的发生率相关。关于单倍型相关性，在调整年龄后，GTT（P=0.001）和 GGTC（P<0.001）单倍型与膀胱癌低发生率相关。相反，TP53 单倍型均与高肿瘤分级或肌肉浸润无关。基于 Cox 回归分析，CGCC 单倍型和侵袭性与癌症相关死亡相关。结构方程模型显示，GGCC 和 CGCC 单倍型对膀胱癌相关死亡的作用相反；GGCC 单倍型是保护因素，而 CGCC 单倍型是危险因素。
TP53 密码子 72 多态性似乎在决定 TP53 单倍型与膀胱癌的发生率和预后的关系方面起着关键作用。需要进一步进行功能测定以确认这些 TP53 单倍型变体是否与 N-Myc 和 NDRG 蛋白相互作用。
