PTEN基因多态性与河北省高发区食管鳞状细胞癌发病风险的关系  

PTEN Polymorphism Association with Esophageal Carcinoma Risk

作　　者：葛晖[1] 曹延延[1] 王益民[1] 张秀凤[1] 李琰[1] 郭炜[1] 王娜[1] 张健慧[1] 

机构地区：[1]河北医科大学第四医院河北省肿瘤研究所分子生物研究室,石家庄市050011

出　　处：《中国肿瘤临床》2007年第22期1261-1265,共5页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30371591);河北省自然科学基金资助(编号:C200400062)

摘　　要：目的:PTEN作为抑癌基因,具有脂质磷酸酶和蛋白磷酸酶的活性,在调节细胞生长、分化和凋亡方面起重要作用。位于PTEN基因第4内含子的一个插入性多态ⅣS4(-/+)可能通过不同剪切来影响其基因表达。本研究旨在探讨河北省食管癌高发区人群中这一常见多态与食管鳞状细胞癌发病风险的关系。方法:采用基于人群的病例-对照研究,以聚合酶链反应-限制性片段长度多态性方法进行基因分型,分析来自食管癌高发区的350例食管癌患者和634例健康对照者的PTEN基因多态性。结果:具有上消化道肿瘤家族史可明显增加食管癌的发病风险,经性别、年龄和吸烟状况校正的OR值为1.73(95%CI=1.29～2.32)。PTENⅣS4基因型在食管癌患者和健康对照中总体分布无显著性差异。与ⅣS4-/-基因型相比携带ⅣS4+/+基因型显著降低食管癌发病风险,校正的OR值为0.64(95%CI=0.44～0.94)。根据吸烟状况和上消化道肿瘤家族史进行分层分析,发现在有上消化道肿瘤家族史个体中携带ⅣS4-/+基因型降低食管癌的发病风险(校正OR=0.55,95%CI=0.34～0.90),而在吸烟个体、非吸烟个体及上消化道肿瘤家族史阴性个体中PTENⅣS4-/+、+/+基因型均不影响食管鳞状细胞癌的发病风险。结论:PTENⅣS4+/+基因型是河北省食管癌高发区食管鳞状细胞癌发生的保护性因素,此外PTENⅣS4-/+基因型仅降低家族集聚性食管癌的发病风险。Objective： PTEN, a tumor suppressor gene with lipid and protein phosphatase activities, plays an important role in regulating cell growth, proliferation, and apoptosis. An insertion poly- morphism in intron 4 of the PTEN gene ⅣS4 （-/＋）, by a different splice variant that influences the expression of PTEN. This study was designed to investigate the association of this common polymorphism with the risk of esophageal squamous cell cancer （ESCC） in a high incidence region of Hebei province. Methods： We conducted a population-based case-control study in 350 ESCC patients and 634 healthy controls. The PTEN genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results： The results showed that a family history of upper gastrointestinal cancer（UGIC） significantly increased the risk of ESCC（age, sex and smoking status were adjusted; OR= 1.73, 95% CI=1.29-2.32）. The overall distribution of the PTEN ⅣS4 genotype was not significantly different between cancer patients and the controls. Compared with the PTEN Ⅳ S4-/- genotype, the PTEN Ⅳ S4＋/＋ genotype significantly decreased the risk of developing ESCC （adjusted OR=0.64, 95% CI=0.44-0.94）. Stratification analysis by smoking status and family history of UGIC revealed that the PTEN ⅣS4-/＋ genotype reduced the risk of ESCC（adjusted OR=0.55, 95% CI=0.34-0.90） among subjects with UGIC family history. Alternatively, the PTEN ⅣS4-/＋ and PTEN ⅣS4＋/＋ genotype did not show a significant effect on the risk of ESCC among smokers, non-smokers and subjects without UGIC family history. Conclusion： Our results suggested that the PTEN ⅣS4＋/＋ homozygous genotype plays a protective role in the development of ESCC in a high incidence region of Hebei province. In addition, the PTEN ⅣS4-/＋ genotype only reduced the risk of familial ESCC.

关 键 词：PTEN基因 食管鳞状细胞癌 基因多态性 

分 类 号：R735.1[医药卫生—肿瘤]