蘇州大學醫(yī)學部張洪濤教授指導的碩士生雷哲,、劉仍允的研究論文“TGFBR1 haplotypes and risk of non-small cell lung cancer”于2009年9月1日發(fā)表在Cancer Research上。
張洪濤教授領導的肺癌分子遺傳學研究課題組在既往一系列有關TGFBR1基因與肺癌關系研究的基礎上,，創(chuàng)新性地假設TGFBR1單倍型可能與非小細胞肺癌（NSCLC）的遺傳易感性相關,，并對此假設進行了驗證,。課題組在470個隊列研究樣本中，對TGFBR1基因序列上的7個單倍型標簽SNP（htSNP）進行了基因分型,，然后根據7個htSNP的基因分型數據和遺傳連鎖不平衡狀況進行了單倍型重構,。研究發(fā)現：單個htSNP與NSCLC的遺傳易感性沒有相關性；然而,，1個四位點的單倍型（CTGC）卻對降低NSCLC的發(fā)病風險有著顯著的貢獻（adjusted OR,0.11;95% CI,0.03-0.39;P<0.0007）。該研究為預防NSCLC提供了重要的線索。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
