Tandle A T, Sanghvi V, Saranath D
Laboratory of Cancer Genes, Cancer Research Institute, Parel, Mumbai, India.
Br J Cancer. 2001 Mar 23;84(6):739-42. doi: 10.1054/bjoc.2000.1674.
The p53 tumour suppressor gene is inactivated in various types of human cancers, and has been implicated as an early event in several cancers. A p53 Pro/Arg polymorphism at exon 4 codon 72, has been suggested to be involved in susceptibility to cancers as well. Hence, in the current study, we investigated p53 exon 4 codon 72 polymorphism using Proline or Arginine specific primers from the peripheral blood cells (PBC) representing constitutional DNA from 72 oral cancer patients. PBC from 153 normal healthy individuals were used to determine the frequency of the p53 genotypes, Pro/Pro, Arg/Arg and Pro/Arg, in the Indian population. The frequency of distribution of genotypes in the normal healthy individuals was, Pro/Pro - 0.20 (31/153), Arg/Arg -- 0.14 (22/153) and Pro/Arg -- 0.65 (100/153); and in the oral cancer patients was, Pro/Pro -- 0.19 (14/72), Arg/Arg -- 0.08 (6/72) and Pro/Arg -- 0.72 (52/72). Thus, we observed an equidistribution of the genotypes in normal control and oral cancer patients (chi(2)= 1.77, df = 2, 0.3 <P< 0.5). Further, DNA from corresponding tumours from the 72 oral cancer patients were examined for loss of heterozygosity in the p53 gene. Allelic loss was observed in 8 of 52 (15%) heterozygous informative oral cancer patients. Our data indicates an equidistribution of the genotypes and absence of over-representation of either Pro/Pro or Arg/Arg genotypes in the oral cancer patients as compared to the normal healthy controls. Hence, association of the p53 genotypes with susceptibility to oral cancer, was not observed.
p53肿瘤抑制基因在多种人类癌症中失活,并且被认为是几种癌症的早期事件。第4外显子72密码子处的p53脯氨酸/精氨酸多态性也被认为与癌症易感性有关。因此,在本研究中,我们使用脯氨酸或精氨酸特异性引物,从72例口腔癌患者代表其体质DNA的外周血细胞(PBC)中研究了p53第4外显子72密码子多态性。使用153名正常健康个体的PBC来确定印度人群中p53基因型(脯氨酸/脯氨酸、精氨酸/精氨酸和脯氨酸/精氨酸)的频率。正常健康个体中基因型的分布频率为:脯氨酸/脯氨酸-0.20(31/153),精氨酸/精氨酸-0.14(22/153),脯氨酸/精氨酸-0.65(100/153);口腔癌患者中为:脯氨酸/脯氨酸-0.19(14/72),精氨酸/精氨酸-0.08(6/72),脯氨酸/精氨酸-0.72(52/72)。因此,我们观察到正常对照和口腔癌患者中基因型分布均衡(χ2 = 1.77,自由度= 2,0.3 <P< 0.5)。此外,对72例口腔癌患者相应肿瘤的DNA进行了p53基因杂合性缺失检测。在52例(15%)杂合信息性口腔癌患者中有8例观察到等位基因缺失。我们的数据表明,与正常健康对照相比,口腔癌患者中基因型分布均衡,且脯氨酸/脯氨酸或精氨酸/精氨酸基因型均未过度表现。因此,未观察到p53基因型与口腔癌易感性之间的关联。