Lo Su-Shun, Lin Shu-Chun, Wu Chew-Wun, Chen Jen-Hao, Yeh Wen-I, Chung Ming-Yi, Lui Win-Yiu
Division of General Surgery, Taipei Veterans General Hospital and National Yang Ming University, No 201, Sec 2, Shih-Pai Rd, Taipei, Taiwan.
Ann Surg Oncol. 2007 Aug;14(8):2250-6. doi: 10.1245/s10434-006-9290-7. Epub 2007 May 23.
Heme oxygenase-1 (HO-1) gene, which encodes an oxidative response protein, plays a role in cytoprotection. A (GT)n dinucleotide repeat in HO-1 promoter is polymorphic and modulates the transcriptional activity of the gene. A HO-1 gene promoter polymorphism was reported to be associated with the risks of lung adenocarcinoma and oral squamous cancer. In this study, the correlation between the HO-1 gene promoter polymorphism and the clinicopathological characteristics, along with the risk of gastric cancer, was analyzed.
We examined the genotypic frequencies of (GT)n repeats in 183 gastric cancer patients and 250 control subjects by PCR-based genotyping and DNA sequencing. The length polymorphisms of (GT)n repeats were classified into short (S) component (n <or= 25), medium (M) component (26 <or= n <or= 30) and long (L) component (n >or= 31). The distribution of S, M and L components in patient and control groups were evaluated to determine the correlation with susceptibility and clinicopathological characteristics of gastric adenocarcinoma.
Higher frequencies of L-allele, L-allele carrier (S/L, M/L, L/L) and S/L genotype were found in gastric cancer patients. The frequencies of M-allele, M-allele carrier (M/M, M/L, M/S) and M/M genotype were significantly lower in patients with gastric cancer than controls. Furthermore, the frequency of lymphovascular tumor invasion was significantly lower in M-allele carriers compared to non-M-allele carriers (S/S, S/L, L/L) (p = 0.009).
These findings suggest that the long (GT)n repeat of HO-1 gene promoter was associated with a higher frequency of gastric adenocarcinoma, and the medium (GT)n repeat might possess protective effect against gastric adenocarcinoma with a lower frequency of lymphovascular invasion in tumors.
血红素加氧酶-1（HO-1）基因编码一种氧化应激反应蛋白，在细胞保护中发挥作用。HO-1启动子中的（GT）n二核苷酸重复序列具有多态性，可调节该基因的转录活性。据报道，HO-1基因启动子多态性与肺腺癌和口腔鳞状细胞癌的风险相关。在本研究中，分析了HO-1基因启动子多态性与胃癌临床病理特征以及胃癌风险之间的相关性。
我们通过基于PCR的基因分型和DNA测序，检测了183例胃癌患者和250例对照受试者中（GT）n重复序列的基因型频率。（GT）n重复序列的长度多态性分为短（S）组分（n≤25）、中（M）组分（26≤n≤30）和长（L）组分（n≥31）。评估患者组和对照组中S、M和L组分的分布，以确定其与胃腺癌易感性和临床病理特征的相关性。
在胃癌患者中发现L等位基因、L等位基因携带者（S/L、M/L、L/L）和S/L基因型的频率较高。胃癌患者中M等位基因、M等位基因携带者（M/M、M/L、M/S）和M/M基因型的频率显著低于对照组。此外，与非M等位基因携带者（S/S、S/L、L/L）相比，M等位基因携带者的淋巴管肿瘤侵犯频率显著降低（p = 0.009）。
这些发现表明，HO-1基因启动子的长（GT）n重复序列与胃腺癌的较高频率相关，而中（GT）n重复序列可能对胃腺癌具有保护作用，肿瘤中淋巴管侵犯的频率较低。
