p73基因多态性与食管癌、贲门癌遗传易感性的关系

背景与目的:p73作为一种抑癌基因,其第二外显子非编码区存在两个单核苷酸多态性(G4C14-A4T14),可以形成茎环结构而影响基因表达。本研究旨在探讨河北省食管癌高发区人群中这两个连锁多态性与食管癌、贲门癌易感性的关系。方法:采用病例-对照研究,以聚合酶链反应-限制性片段长度多态性方法,分析348例食管癌患者、259例贲门癌患者和630例健康对照者的p73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和贲门癌的发病风险,经性别、年龄和吸烟状况校正的OR值分别1.68(95%CI=1.28～2.20)和1.68(95%CI=1.24～2.26)。p73G4C14-A4T14基因型及等位基因型在食管癌患者、贲门癌患者和健康对照中总体分布差异无显著性。在根据吸烟状况和上消化道肿瘤家族史进行分层分析,发现在无上消化道肿瘤家族史亚组中,携带GC/AT基因型明显增加贲门癌的发病风险(OR=1.71,95%CI=1.14～2.57),而其他亚组中未见p73G4C14-A4T14多态性增加食管癌、贲门癌的发病风险。结论:p73G4C14-A4T14多态性中,携带GC/AT基因型明显增加河北省食管癌高发区无上消化道肿瘤家族史人群贲门癌的发病风险。

Correlation of p73 polymorphisms to genetic susceptibilities to esophageal carcinoma and gastric cardiac carcinoma

BACKGROUND & OBJECTIVE: p73 is a tumor suppressor gene. The two polymorphisms in the non-coding region of the exon 2 of p73 gene, named G4C14-A4T14, can form a stem-loop structure, and may influence p73 expression. This study was to investigate the correlation of p73 G4C14-A4T14 polymorphisms to susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a high incidence region of Hebei Province. METHODS: We conducted a population-based case-control study in 348 ESCC patients, 259 GCA patients, and 630 healthy controls. p73 genotypes were determined by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). RESULTS: Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA [the age, sex, and smoking status adjusted odds ratio (OR)=1.68, 95% confidence interval (CI)=1.28-2.20; OR=1.68, 95% CI=1.24-2.26, respectively]. The overall distribution of p73 genotype and allelotype in cancer patients and controls were not significantly different. Stratification analysis by smoking status and family history of UGIC found that the GC/AT genotype significantly increased the risk of developing GCA among the subjects without family history of UGIC (OR=1.71, 95% CI=1.14-2.57), while p73 G4C14-A4T14 polymorphisms didn't increase the risk of developing ESCC and GCA in other subgroups. CONCLUSION: In p73 G4C14-A4T14 polymorphisms, the GC/AT genotype increases the risk of developing GCA among the subjects without family history of UGIC.