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台湾地区食管鳞状细胞癌中p53基因突变风险与嚼食槟榔习惯

Risk of p53 gene mutation in esophageal squamous cell carcinoma and habit of betel quid chewing in Taiwanese.

作者信息

Goan Yih-Gang, Chang Huang-Chou, Hsu Hon-Ki, Chou Yi-Pin, Cheng Jiin-Tsuey

机构信息

Department of Surgery, Kaohsiung Veterans General Hospital, Taiwan, Republic of China.

出版信息

Cancer Sci. 2005 Nov;96(11):758-65. doi: 10.1111/j.1349-7006.2005.00115.x.

Abstract

A recent report suggested that BQ (BQ) chewing significantly correlated with the occurrence of esophageal squamous cell carcinoma (ESCC) in Taiwanese. BQ chewing was shown to be associated with p53 mutation in oral cancers. However, the relationship between BQ chewing and p53 mutation in ESCC is unclear. Seventy-five primary ESCC patients were enrolled for mutational analysis of the p53 gene using polymerase chain amplification and direct sequencing of amplified product. Thirty-seven mutations of the p53 gene were detected in 45.5% (34/75) of tumor specimens. These mutations significantly clustered in exon 5 (21/37) of the p53 gene. The incidence of p53 mutations did not associate with clinicopathological characteristics or the habits of cigarette smoking or alcohol consumption. However, BQ chewers exhibited significantly higher incidence of p53 gene mutations than non-chewers (67.6% vs 32.4%, P = 0.007). After controlling the confounding factors of cigarette smoking and alcohol intake, BQ chewing still showed significant association with the incidence of p53 mutation in ESCCs (RR = 4.23; 95% CI, 1.317-13.60). The A:T to G:C transition (8/37, 21.6%) and G:C to T:A transversion (5/23, 13.5%) were the prevalent spectrum of p53 gene mutations. All A:T to G:C transitional mutations occurred in patients with the habits of BQ chewing and cigarette smoking. Noticeably, alcohol consumption could enhance this peculiar spectrum of p53 mutation in ESCC. Accordingly, p53 might be an important molecular target of BQ carcinogens in the development of ESCC in Taiwanese.

摘要

最近的一份报告表明,嚼槟榔与台湾地区食管鳞状细胞癌(ESCC)的发生显著相关。嚼槟榔与口腔癌中的p53突变有关。然而,嚼槟榔与ESCC中p53突变之间的关系尚不清楚。招募了75例原发性ESCC患者,采用聚合酶链扩增和扩增产物直接测序法对p53基因进行突变分析。在45.5%(34/75)的肿瘤标本中检测到37个p53基因突变。这些突变主要集中在p53基因的第5外显子(21/37)。p53突变的发生率与临床病理特征或吸烟及饮酒习惯无关。然而,嚼槟榔者的p53基因突变发生率显著高于不嚼槟榔者(67.6%对32.4%,P = 0.007)。在控制了吸烟和饮酒的混杂因素后,嚼槟榔仍与ESCC中p53突变的发生率显著相关(RR = 4.23;95%CI,1.317 - 13.60)。A:T到G:C的转换(8/37,21.6%)和G:C到T:A的颠换(5/23,13.5%)是p53基因突变的主要类型。所有A:T到G:C的转换突变均发生在有嚼槟榔和吸烟习惯的患者中。值得注意的是,饮酒可增强ESCC中这种特殊的p53突变类型。因此,p53可能是台湾地区ESCC发生过程中槟榔致癌物的重要分子靶点。

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