Polymorphisms in the Transforming Growth Factor Beta 1 Pathway in Relation to Colorectal Cancer Progression
Polymorphisms in the Transforming Growth Factor Beta 1 Pathway in Relation to Colorectal Cancer Progression
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DOI：
10.1002/gcc.20738
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发表时间：
2010-03-01
影响因子：
3.7
通讯作者：
Lenner, Per
中科院分区：
文献类型：
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作者：
Foersti, Asta;Li, Xuchen;Lenner, Per
转化生长因子- 1 （TGFB1）作为正常结肠上皮细胞的生长抑制剂，但作为结直肠癌（CRC）细胞的肿瘤启动子。为了探索TGFB1通路遗传多态性与CRC易感性和临床结局之间的关系，我们对瑞典308例CRC病例和585例年龄和性别匹配的对照组进行了病例对照研究。这些病例是前瞻性取样的，并进行了长达16年的随访，这使得研究材料特别适合于生存分析。根据已报道或预测的功能作用，选择9个单核苷酸多态性（TGFB1: Leu10Pro； TGFBR1: 9A/6A和IVS7G+24A； FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G； LTBP4: T- 893g和Thr750Ala； BAMB1: T- 779a）进行基因分型。我们评估了基因型与结直肠癌和Dukes分期之间的关系。比较不同亚组间的生存概率。观察到的具有统计学意义的关联包括TGFBR1 IVS7G+24A小等位基因携带者的结直肠癌风险降低（优势比（OR）： 0.72, 95%可信区间（CI）： 0.53-0.97）， LTBP4 Thr750Ala和BAMB1 T-779A小等位基因携带者的Dukes a +B期肿瘤的侵略性降低（OR: 0.58, 95%CI: 0.36-0.93和OR: 0.51, 95%CI: 0.29-0.89）， FURIN C-229T杂合子的生存率较差（风险比：1.63,95%CI: 1.08-2.46）。由于这是第一个关于TGFBI通路多态性对CRC进展影响的研究，因此需要在大型独立队列中进行进一步的研究。(C) 2009 Wiley-Liss, Inc。
Transforming growth factor beta 1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMB1: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMB1 T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFBI pathway on CRC progression, further studies in large independent cohorts are warranted. (C) 2009 Wiley-Liss, Inc.