Singamsetty Gopi Krishna, Malempati Sravanthi, Bhogadhi Srichandana, Kondreddy Ravinder, Govatati Suresh, Tangudu Naveen Kumar, Govatati Sowdamani, kuraganti Anil Kumar, Bhanoori Manjula, Kassetty Kondaiah
Department of Zoology, Acharya Nagarjuna University, Guntur, India.
Tumour Biol. 2014 Mar;35(3):2303-11. doi: 10.1007/s13277-013-1305-y. Epub 2013 Oct 26.
The objective of the present study was to investigate the association between TP53 gene single nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) predisposition in south Indian population and to evaluate the role of TP53 expression in the pathophysiology of CRC. A genetic association study was conducted in 103 CRC cases and 107 controls of south Indian origin. We genotyped ten selected TP53 SNPs by polymerase chain reaction-sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand the role of TP53 in the pathophysiology of CRC, the expression pattern was evaluated in analogous tumor and normal tissues from 23 CRC patients by Western blot analysis. The frequencies of Pro72Pro (P = 0.0033) genotype and Ser47/Pro72 (P = 0.00171) haplotype were significantly higher in patients as compared to controls. Strong LD was observed between codon 47 and 72 in cases (D' = 0.32) as compared to controls (D' = 0.21). The polymorphism was not observe at the remaining eight SNPs loci analyzed. Furthermore, increased TP53 expression was observed in tumor tissue than in analogous normal tissue of CRC patients. Interestingly, advanced stage tumors showed more elevated TP53 expression compared to early stage tumors. In conclusion, the TP53 Pro72Pro genotype and Ser47/Pro72 haplotype has an increased risk for CRC predisposition in south Indian population. In addition, elevated TP53 expression appears to be useful prognostic marker for CRC.
本研究的目的是调查TP53基因单核苷酸多态性（SNP）与印度南部人群结直肠癌（CRC）易感性之间的关联，并评估TP53表达在CRC病理生理学中的作用。对103例印度南部起源的CRC病例和107例对照进行了基因关联研究。我们通过聚合酶链反应测序分析对十个选定的TP53 SNP进行基因分型。使用Haploview软件评估多个位点的单倍型频率和成对连锁不平衡（LD）的标准化不平衡系数（D'）。此外，为了更好地了解TP53在CRC病理生理学中的作用，通过蛋白质印迹分析评估了23例CRC患者的类似肿瘤组织和正常组织中的表达模式。与对照组相比，患者中Pro72Pro（P = 0.0033）基因型和Ser47/Pro72（P = 0.00171）单倍型的频率显著更高。与对照组（D' = 0.21）相比，病例组中密码子47和72之间观察到强LD（D' = 0.32）。在分析的其余八个SNP位点未观察到多态性。此外，与CRC患者的类似正常组织相比，肿瘤组织中观察到TP53表达增加。有趣的是，与早期肿瘤相比，晚期肿瘤显示出更高的TP53表达。总之，TP53 Pro72Pro基因型和Ser47/Pro72单倍型在印度南部人群中患CRC的易感性风险增加。此外，TP53表达升高似乎是CRC的有用预后标志物。
