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Cancer Research:TGFBR1单倍型与非小细胞肺癌遗传易感性

来源:生物通 2009-09-02 09:34

苏州大学医学部张洪涛教授指导的硕士生雷哲、刘仍允的研究论文“TGFBR1 haplotypes and risk of non-small cell lung cancer”于2009年9月1日发表在Cancer Research上。

张洪涛教授领导的肺癌分子遗传学研究课题组在既往一系列有关TGFBR1基因与肺癌关系研究的基础上,创新性地假设TGFBR1单倍型可能与非小细胞肺癌(NSCLC)的遗传易感性相关,并对此假设进行了验证。课题组在470个队列研究样本中,对TGFBR1基因序列上的7个单倍型标签SNP(htSNP)进行了基因分型,然后根据7个htSNP的基因分型数据和遗传连锁不平衡状况进行了单倍型重构。研究发现:单个htSNP与NSCLC的遗传易感性没有相关性;然而,1个四位点的单倍型(CTGC)却对降低NSCLC的发病风险有着显著的贡献(adjusted  OR,0.11;95% CI,0.03-0.39;P<0.0007)。该研究为预防NSCLC提供了重要的线索。(生物谷Bioon.com)

生物谷推荐原始出处:

Cancer Research, 10.1158/0008-5472.CAN-08-4602

TGFBR1 Haplotypes and Risk of Non–Small-Cell Lung Cancer

Zhe Lei 1, Reng-Yun Liu 1, Jun Zhao 1, 2, Zeyi Liu 1, Xiefang Jiang 1, Weiming You 3, Xiao-Feng Chen 1, 4, Xia Liu 1, Kui Zhang 5, Boris Pasche 6, and Hong-Tao Zhang 1*

1Laboratory of Medical Genetics, School of Basic Medicine and Biological Sciences and 2Department of Surgery, The First Affiliated Hospital, Medical College of Soochow University, Suzhou, P.R. China; 3Division of Clinical Medicine, Wuxi Third People's Hospital, Wuxi, P.R. China; 4Department of Surgery, Shanghai Hospital for Pulmonary Diseases, Shanghai, P.R. China; 5Department of Biostatistics, School of Public Health and 6Division of Hematology/Oncology, Department of Medicine and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama

Transforming growth factor  (TGF-) receptors are centrally involved in TGF-–mediated cell growth and differentiation and are frequently inactivated in non–small-cell lung cancer (NSCLC). Constitutively decreased type I TGF- receptor (TGFBR1) expression is emerging as a novel tumor-predisposing phenotype. The association of TGFBR1 haplotypes with risk for NSCLC has not yet been studied. We tested the hypothesis that single-nucleotide polymorphisms (SNP) and/or TGFBR1 haplotypes are associated with risk of NSCLC. We genotyped six TGFBR1 haplotype-tagging SNPs (htSNP) by PCR-RFLP assays and one htSNP by PCR-single-strand conformation polymorphism assay in two case-control studies. Case-control study 1 included 102 NSCLC patients and 104 healthy controls from Suzhou. Case-control study 2 included 131 patients with NSCLC and 133 healthy controls from Wuxi. Individuals included in both case-control studies were Han Chinese. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of these seven htSNPs. None of the htSNP was associated with NSCLC risk in either study. However, a four-marker CTGC haplotype was significantly more common among controls than among cases in both studies (P = 0.014 and P = 0.010, respectively), indicating that this haplotype is associated with decreased NSCLC risk {adjusted odds ratio [OR], 0.09 [95% confidence interval (95% CI), 0.01–0.61] and 0.11 [95% CI, 0.02–0.59], respectively}. Combined analysis of both studies shows a strong association of this four-marker haplotype with decreased NSCLC risk (adjusted OR, 0.11; 95% CI, 0.03–0.39). This is the first evidence of an association between a TGFBR1 haplotype and risk for NSCLC.

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