Single nucleotide polymorphism at codon 133 of the RASSF1 gene is preferentially associated with human lung adenocarcinoma risk
Single nucleotide polymorphism at codon 133 of the RASSF1 gene is preferentially associated with human lung adenocarcinoma risk
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DOI：
10.1016/j.canlet.2005.07.006
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发表时间：
2006-07-08
期刊：
影响因子：
9.7
通讯作者：
Shimizu, Kenji
中科院分区：
文献类型：
--
作者：
Kanzaki, Hirotaka;Hanafusa, Hiroko;Shimizu, Kenji
RASSF1基因是一种假定的肿瘤抑制基因，位于人类染色体3p21上，由于在多种人类恶性肿瘤中频繁出现的等位基因丢失和启动子高甲基化导致的基因沉默而备受关注。编码丙氨酸 (GCT) 或丝氨酸 (TCT) 的 RASSF1 基因密码子 133 处的单核苷酸多态性 (SNP) 与人类癌症风险之间的关联仍不清楚。因此，我们通过聚合酶链反应和限制性内切酶消化测定法研究了 101 名肺癌患者、63 名头颈癌患者、72 名结直肠癌患者、56 名食道癌患者和 110 名健康对照患者中 Ala133Ser SNP 的分布。肺癌患者中杂合的 Ala/Ser 基因型显着高于健康对照（P = 0.028）。与具有 Ala/Ala 基因型的对照相比，具有杂合 Ala/Ser 基因型的患者的调整优势比 (OR) 为 2.59（95% 置信区间 (CI)；1.11-6.04）。在肺癌患者中发现了 Ala/Ser 基因型的风险增加，但在我们检查的其他癌症患者中没有发现。这种关联在男性肺癌患者（调整后的 OR；3.33，95% CI；1.37-8.12）、与腺癌（调整后的 OR；3.33，95% CI；1.36-8.15）、早期肺癌（调整后的 OR；3.42，95% CI；1.33-8.75）和吸烟习惯（调整后的 OR；3.33，95% CI；1.36-8.15）和吸烟习惯（调整后的 OR；3.42，95% CI；1.33-8.75）之间的相关性特别强。 2.70，95% CI；1.06-6.83）。这些结果表明RASSF1 Ala133Ser SNP与肺癌，特别是肺腺癌的发生有关。杂合基因型的风险增加很有趣，这意味着与 RASSF1 蛋白的二聚化特征密切相关。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
The RASSF1 gene, a putative tumor suppressor gene located on human chromosome 3p21, gamers much attention for the frequent allelic loss and gene silencing via promoter hypermethylation in a variety of human malignancies. An association between a single nucleotide polymorphism (SNP) at codon 133 of the RASSF1 gene, encoding either alanine (GCT) or serine (TCT), and human cancer risk remains undefined. We therefore, investigated the distribution of the Ala133Ser SNP in 101 patients with lung cancer, 63 with head and neck cancer, 72 with colorectal cancer, 56 with esophageal cancer and 110 healthy controls by polymerase chain reaction and restriction enzyme-digestion assay. The heterozygous Ala/Ser genotype was significantly more frequent in lung cancer patients than in healthy controls (P = 0.028). The adjusted odds ratio (OR) for the patients with heterozygous Ala/Ser genotype as compared with the controls with the Ala/Ala genotype was 2.59 (95% confidence interval (CI); 1.11-6.04). The increased risk of the Ala/Ser genotype was found in lung cancer patients but not in other cancer patients we examined. The association was particularly strong in those lung cancer patients of male (adjusted OR; 3.33, 95% CI; 1.37-8.12), with adenocarinoma (adjusted OR; 3.33, 95% CI; 1.36-8.15), early stages (adjusted OR; 3.42, 95% CI; 1.33-8.75) and with smoking habit (adjusted OR; 2.70, 95% CI; 1.06-6.83). These results suggest that the RASSF1 Ala133Ser SNP is associated with development of lung cancer, especially of lung adenocarcinoma. The increased risk of the heterozygous genotype is intriguing, implying a close relation with the dimerization feature of RASSF1 proteins. (c) 2005 Elsevier Ireland Ltd. All rights reserved.