Variation_91720拷贝数变异与食管鳞癌易感性的关联研究

Correlation of copy number variation of Variation_ 91720 in PIK3CA gene with susceptibility of esophageal squamous cell carcinoma:a report of 149 patients from Southwest China

目的探讨PIK3CA基因中Variation_91720拷贝数变异（copy number variation,CNV）与中国西南地区汉族人群食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）易感性的关联。方法选取149例中国西南地区ESCC患者和205例年龄、性别相匹配的健康人群作为研究对象,采用基于Taq Man实时定量PCR检测外周血中Variation_91720拷贝数;基于SYBR Green实时定量PCR检测34例ESCC患者癌及癌旁组织中PIK3CA基因mRNA表达量。结果Variation_91720拷贝数在ESCC患者和对照人群中分布有显著差异（P〈0.01）,ESCC患者中Variation_91720拷贝数减少频率显著高于对照人群（P〈0.01,OR=5.617,95%CI=2.750-11.470）,是ESCC发生的危险因素;Variation_91720拷贝数增加显著低于对照人群（P=0.028,OR=0.419,95%CI=0.193-0.911）,是ESCC发生的保护因素。34例ESCC患者中癌组织的PIK3CA基因mRNA表达量显著高于癌旁组织（P=0.038）,基因表达差异与相应的外周血基因组Variation_91720拷贝数变异之间无显著统计学差异（P=0.066）。结论 Variation_91720拷贝数变异与中国西南地区汉族人群ESCC的易感性相关联;其拷贝数减少与增加ESCC的易感性相关而其拷贝数增加与降低ESCC的易感性相关,可能成为ESCC的高危人群筛选和早期诊断生物标记物。

Objective To investigate the correlation of the copy number variation（CNV） of Variation91720 in PIK3 CA gene with the susceptibility of esophageal squamous cell carcinoma（ESCC） in Han population at the Southwest region of China.Methods From the Southwest region,149 ESCC patients and205 healthy controls were selected as the research subjects.The copy number of Variation91720 in peripheral blood was detected by Taq Man real-time fluorescence quantitative polymerase chain reaction（qRT-PCR）,while the mRNA expression of PIK3 CA gene in tumor tissue and adjacent tissue was detected by SYBR Green-based qRT-PCR.Results The copy number distribution of Variation91720 in the ESCC patients was significantly different from that in the healthy controls（P 〈 0.001）.The copy number loss of Variation91720 was found to be a risk factor of ESCC（P 〈 0.001,OR = 5.617,95% CI = 2.750-11.470）,whereas the copy number gain of Variation91720 was a protective factor（P = 0.028,OR = 0.419,95% CI = 0.193-0.911）.In 34 ESCC patients,the PIK3 CA mRNA expression was statistically higher in the tumor tissue than in the adjacent tissue（P = 0.038）,but there was no significant statistical difference between the PIK3 CA mRNA expression and the Variation91720 CNV（P = 0.066）.Conclusion The copy number loss of Variation91720 in PIK3 CA gene may increase the susceptibility to ESCC,whereas the copy number gain of Variation91720 may decrease the susceptibility.Variation91720 may be a biomarker for high-risk population screening and early diagnosis of ESCC.