散发性大肠癌多基因突变与肠道内环境因素关系的研究

A STUDY FOR THE RELATIONSHIP BEWEEN COLONIC CONTENTS AND MILITPLE GENE MUTATIONS IN SPORADIC COLORECTAL CANCER

目的 :探讨肠道内环境中因素与散发性大肠癌多基因突变关系。方法 :对 10 6例散发性大肠癌患者进行多基因突变和肠道内环境中有关指标 (以粪便为标本 )的测定 ,并进行流行病学的病例 -病例研究分析。结果 :10 6例散发性大肠癌患者中APC (MCR) ,K -ras(12 / 13 )及P5 3 (5 / 6,7,8)突变率分别为 3 1.19%(3 2 / 10 6) ,3 7.74% (4 0 / 10 6)及 3 9.62 % (4 2 / 10 6)。散发性大肠癌患者p5 3 2 49密码子突变占 p5 3总突变的42 .86% (18/ 42 ) ;肠道内粪胆汁酸 (OR =1.92 80 ,P =0 .0 0 5 2 ) ,Mg2 +(OR =0 .2 871,P =0 .0 12 1)和Ca2 +(OR=0 .0 65 9,P =0 .0 3 0 7)进入多因素logistic模型 ;吸烟指数和肠道内胆汁酸与 p5 3 2 49密码子突变相关。结论 :散发性大肠癌确实普遍存在有多种基因的突变 ,肠道内高胆汁酸可能是散发性大肠癌相关基因突变的重要危险因素 ,肠道内Ca2 +和Mg2 +可能为保护性因素 ;广东地区散发性大肠癌 p5 3基因突变有一定特点 。

Objective:To explore colonic effect factors for multiple gene mutations in sporadic colorectal cancer(SCC). Methods:Mutations of multiple genes from 106 patients with SCC were analyzed by two multiplex PCR-SSCP systems, PCR-RFLP, and DNA sequencing. Meanwhile, Colonic content examination and case-case study analysis were carried out.Result:The mutation rates of APC(MCR), K-ras(12/13), and p53 (5/6?7?8) were 31.19%(32/106), 37.74%(40/106), and 39.62%(42/106) in SCC respectively. The mutated p53 codon 249 was 42.86% of total p53 (5/6? 7?8)mutation in patients with SCC; Feceai bile acid (fBAD) (OR=1.9280, P= 0.0052), Mg 2+(OR=0.2871, P=0.0121), and Ca 2+ (OR=0.0659, P= 0.0307) could enter multiple logistic regression model;Smoking index and fBAD were showed to related to the mutation of p53 codon 249.Conclusion:The mutation of associated genes was indeed ubiquitous in SCC. Higher colonic fBAD might be an important risk factor for the gene mutations in SCC and colonic fca 2+ and Mg 2+ might be protective factors; The distinguishing mutation profile of p53 was showed in SCC of Guangdong region, so the possible pathogenic role of AFB1 in SCC of Guangdong should be studied.