Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Texas, USA.
Indian J Med Res. 2012 Oct;136(4):664-70.
BACKGROUND & OBJECTIVES: Mutations in the oncogene and tumour suppressor genes play an important role in carcinogenesis. We investigated the association of p53 and K-ras gene mutation and Helicobacter pylori infection in patients with gastric cancer (GC) and peptic ulcer disease (PUD) attending a tertiary care hospital in north India.
In total, 348 adult patients [62 GC, 45 PUD and 241 non-ulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Mutation in the exon 5-8 of p53 gene was analyzed by PCR-single stranded conformational polymorphism (SSCP) and confirmed by sequence analysis. K-ras gene codon 12 mutation was analyzed by PCR-based restriction fragment length polymorphism.
Overall p53 gene mutation was found in 4.6 per cent of the study population, and its distribution in GC, PUD and NUD was 21, 4.4 and 0.4 per cent, respectively. p53 gene mutation was significantly higher in patients with GC than PUD (P<0.05) and NUD (P<0.001). No difference in p53 gene mutation was observed between H. pylori infected and non-infected individuals. K-ras gene mutation was absent in all the patients.
INTERPRETATION & CONCLUSIONS: Our results show that p53 gene mutation may be associated with gastric carcinogenesis independent to H. pylori infection and absence of K-ras gene mutation questions its role in the pathogenesis of GC and PUD in Indian patients.
癌基因和肿瘤抑制基因的突变在肿瘤发生中起着重要作用。我们研究了在印度北部一家三级保健医院就诊的胃癌(GC)和消化性溃疡病(PUD)患者中,p53 和 K-ras 基因突变与幽门螺杆菌(H. pylori)感染的关系。
共纳入 348 例接受上消化道内镜检查的成年患者[62 例 GC、45 例 PUD 和 241 例非溃疡性消化不良(NUD)]。通过快速尿素酶试验、培养、组织病理学和 PCR 诊断 H. pylori 感染。通过 PCR-单链构象多态性(SSCP)分析 p53 基因外显子 5-8 的突变,并通过序列分析进行确认。通过基于 PCR 的限制性片段长度多态性分析 K-ras 基因密码子 12 的突变。
研究人群中总体 p53 基因突变发生率为 4.6%,GC、PUD 和 NUD 中的分布分别为 21%、4.4%和 0.4%。GC 患者的 p53 基因突变发生率明显高于 PUD(P<0.05)和 NUD(P<0.001)。H. pylori 感染和未感染个体之间的 p53 基因突变无差异。所有患者均未发现 K-ras 基因突变。
我们的结果表明,p53 基因突变可能与 H. pylori 感染无关的胃癌发生有关,而 K-ras 基因突变的缺失质疑其在印度患者 GC 和 PUD 发病机制中的作用。