本科生筛得癌症易感基因 文章登国际权威期刊

　　

生物通报道，华中科技大学生命学院苏莉教授带领的研究小组近日在乳腺癌易感基因的筛选方面获得新的成果，相关文章Three common TP53 polymorphisms in susceptibility to breast cancer, evidence from meta-analysis，发表在《Breast Cancer Research and Treatment》上，该杂志2008年影响因子为5.68，是乳腺癌基础与临床研究的国际权威期刊。

 

文章通讯作者是苏莉教授，原武汉大学生命科学学院教师，后赴日本京都大学医学研究科免疫细胞生物学教室学习、工作多年，获博士学位，日本学术振兴会博士后研究员。主要从事小分子G蛋白Rap1在生物体内信号传导通路及调控癌症发生和恶化转移的研究。2005年赴美国斯坦福研究所国际健康科学中心将研究兴趣扩展至人类遗传学及基因组学研究。现加盟华中科技大学生命科学与技术学院，继续揭示小分子G蛋白在人类疾病中的功用。

 

文章的第一作者是华中科技大学创新基地06级本科生胡政、07级本科生李想同学。除这篇文章外，胡政、李想等同学已有多篇学术论文被核心期刊录用：1.   胡政，李想，冯茂辉，储君君，谢伟. 乳腺癌风险评估预测的模型及应用. 中华流行病学杂志,2009;30(10):85-89.  2.   赵春风，胡政. 用于构建人工大脑的神经网络模型的分析与评估. 计算机应用, 2009; 29:326-328. (并列第一作者)

 

筛查肿瘤易感性单核苷酸多态性（SNP）位点一直是肿瘤基础研究的一个热点，它为确定高危人群、寻找预警标志物及个体化医疗提供理论依据。胡政等同学利用课余时间从文献中大规模筛查乳腺癌病例-对照样本（总病例23,567例，正常对照25,995例），通过meta-analysis，对三个TP53基因多态性位点与乳腺癌患病风险进行关联研究。首次发现其中一个多态位点，即72号密码子精氨酸到脯氨酸的变化，与乳腺癌患病风险的关联受地域和人种影响，该变异在地中海人群中可以显著降低患病风险。此外，大规模数据的关联分析显示，另外一个多态位点，即3号内含子内一段16个碱基的插入，可以显著增加患乳腺癌风险，该多态位点可能是乳腺癌的一个新的预警标记物。

 

胡政、李想等同学自加入创新基地“乳腺癌易感性基因的筛查”项目小组的研究工作以来，一直在苏莉教授的指导下开展科研工作，通过样本对照实验和关联分析，筛查乳腺癌易感性SNP位点，并结合流行病学的风险因子进行乳腺癌的风险评估与预测。已完成几十个候选SNP的筛选，250余例乳腺癌及正常对照血液样本的收集和DNA提取鉴定，候选SNP的基因分型和关联分析，已鉴别出多个关联性多态位点。

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生物通推荐原文检索

Three common TP53 polymorphisms in susceptibility to breast cancer, evidence from meta-analysis

Zheng Hu1, Xiang Li1, Rong Yuan2, Brian Z. Ring3 and Li Su1

 

(1)  Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, 430074 Wuhan, China

(2)  Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

(3)  Department of Research and Development, Applied Genomics Inc, Burlingame, CA, USA

 

Received: 7 June 2009  Accepted: 18 July 2009  Published online: 6 August 2009

 

Abstract  The association of polymorphisms of tumor suppressor gene TP53 with breast cancer has widely been reported; however, the results are inconsistent. Here, we selected three commonly studied TP53 polymorphisms: codon 72 Arg > Pro, IVS3 16 bp Del/Ins, and IVS6 + 62A > G to explore their association with breast cancer risk by meta-analysis of published case–control studies. The results showed that codon 72 was not associated with breast cancer risk among 37 combined case–control studies (23,567 cases and 25,995 controls). However, a significant association with decreased risk of breast cancer was found in the Mediterranean studies (PP + PR vs. RR: OR = 0.32, 95% CI = 0.24−0.44, P < 0.001; PP vs. RR: OR = 0.35, 95% CI = 0.21−0.60, P < 0.001). IVS3 16 bp Del/Ins was significantly associated with an increased risk of developing breast cancer in a pooled 8 study dataset (2,470 cases and 2,825 controls; Ins/Ins + Del/Ins vs. Del/Del: OR = 1.15, 95% CI = 1.01−1.30, P = 0.04; Ins/Ins vs. Del/Del: OR = 1.75, 95% CI = 1.20−2.37, P = 0.003). No significant association was observed between IVS6 + 62A > G and breast cancer risk in a total of 10 studies (8,537 cases and 9,586 controls). These results suggest that IVS3 16 bp Del/Ins is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 has a potential role in association with breast cancer risk within certain populations or regions.

Electronic supplementary material  The online version of this article (doi:10.1007/s10549-009-0488-9) contains supplementary material, which is available to authorized users.

Keywords   TP53  - Breast cancer - Polymorphism - Susceptibility - Meta-analysis