结肠直肠癌是工业化国家最常见的癌症。8月14日在线出版Science杂志刊发了最新研究论文，揭示了TGFBR1基因的变异体是促使某些人易患结肠直肠癌的遗传因子。
以前的研究已知，TGF-beta 信号通路对结肠直肠癌和其他肿瘤细胞的生长具有调控作用。而TGFBR1基因负责编码该信号通路中的一个成员。Laura Valle等在美国俄亥俄州中部地区开展的研究发现，在结肠直肠癌病人中，有10%~20%的人的两个等位（拷贝）TGFBRI 基因中仅有1个被转录；在对照组中，这一数字仅为1%~3%。这种等位基因的不平衡，导致携带者在其一生中TGFBR1基因的表达都会有轻微的降低，从而使得携带者罹患结肠直肠癌的风险增加。Laura Valle估计该地区所有结肠直肠癌病例中，大约有10%与该遗传风险因子有关联。（生物谷Bioon.com）
生物谷推荐原始出处：
Science，DOI: 10.1126/science.1159397，Laura Valle, Boris Pasche, Stephan M. Tanner, Albert de la Chapelle
Germline Allele-specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer
Laura Valle 1, Tarsicio Serena-Acedo 1, Sandya Liyanarachchi 1, Heather Hampel 1, Ilene Comeras 1, Zhongyuan Li 1, Qinghua Zeng 2, Hong-Tao Zhang 2, Michael J. Pennison 2, Maureen Sadim 2, Boris Pasche 2*, Stephan M. Tanner 1*, Albert de la Chapelle 1*
1 Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
2 Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Much of the genetic predisposition to colorectal cancer (CRC) in humans is unexplained. Studying a Caucasian-dominated population in the United States, we show that germline allele-specific expression (ASE) of the gene encoding transforming growth factor– type I receptor, TGFBR1, is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls. ASE results in reduced expression of the gene, is dominantly inherited, segregates in families, and occurs in sporadic CRC cases. Although subtle, the reduction in constitutive TGFBR1 expression alters SMAD-mediated transforming growth factor– signaling. Two major TGFBR1 haplotypes are predominant among ASE cases, which suggests ancestral mutations, but causative germline changes have not been identified. Conservative estimates suggest that ASE confers a substantially increased risk of CRC (odds ratio 8.7; 95% confidence interval: 2.6 to 29.1), but these estimates require confirmation and likely will show ethnic differences.
