Lei Zhe, Liu Reng-Yun, Zhao Jun, Liu Zeyi, Jiang Xiefang, You Weiming, Chen Xiao-Feng, Liu Xia, Zhang Kui, Pasche Boris, Zhang Hong-Tao
Laboratory of Medical Genetics, School of Basic Medicine and Biological Sciences, The First Affiliated Hospital, Medical College of Soochow University, Suzhou, PR China.
Cancer Res. 2009 Sep 1;69(17):7046-52. doi: 10.1158/0008-5472.CAN-08-4602. Epub 2009 Aug 18.
Transforming growth factor beta (TGF-beta) receptors are centrally involved in TGF-beta-mediated cell growth and differentiation and are frequently inactivated in non-small-cell lung cancer (NSCLC). Constitutively decreased type I TGF-beta 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.
转化生长因子β（TGF-β）受体在TGF-β介导的细胞生长和分化过程中起核心作用，且在非小细胞肺癌（NSCLC）中常发生功能失活。I型TGF-β受体（TGFBR1）表达的持续性降低正成为一种新的肿瘤易感性表型。TGFBR1单倍型与NSCLC风险之间的关联尚未得到研究。我们检验了单核苷酸多态性（SNP）和/或TGFBR1单倍型与NSCLC风险相关的假设。在两项病例对照研究中，我们通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对6个TGFBR1单倍型标签SNP（htSNP）进行基因分型，并通过聚合酶链反应-单链构象多态性分析对1个htSNP进行基因分型。病例对照研究1纳入了来自苏州的102例NSCLC患者和104名健康对照。病例对照研究2纳入了来自无锡的131例NSCLC患者和133名健康对照。两项病例对照研究中的个体均为汉族。根据这7个htSNP的基因分型数据和连锁不平衡状态重建单倍型。在两项研究中，均没有htSNP与NSCLC风险相关。然而，在两项研究中，一种四标记CTGC单倍型在对照中均显著比病例中更常见（P值分别为0.014和0.010），表明这种单倍型与NSCLC风险降低相关{调整后的优势比[OR]分别为0.09[95%置信区间（95%CI），0.01 - 0.61]和0.11[95%CI，0.02 - 0.59]}。两项研究的联合分析显示，这种四标记单倍型与NSCLC风险降低密切相关（调整后的OR为0.11；95%CI，0.03 - 0.39）。这是TGFBR1单倍型与NSCLC风险之间存在关联的首个证据。
