結(jié)腸直腸癌是工業(yè)化國(guó)家最常見(jiàn)的癌癥,。8月14日在線出版Science雜志刊發(fā)了最新研究論文，揭示了TGFBR1基因的變異體是促使某些人易患結(jié)腸直腸癌的遺傳因子,。
以前的研究已知，TGF-beta 信號(hào)通路對(duì)結(jié)腸直腸癌和其他腫瘤細(xì)胞的生長(zhǎng)具有調(diào)控作用,。而TGFBR1基因負(fù)責(zé)編碼該信號(hào)通路中的一個(gè)成員,。Laura Valle等在美國(guó)俄亥俄州中部地區(qū)開(kāi)展的研究發(fā)現(xiàn)，在結(jié)腸直腸癌病人中,，有10%~20%的人的兩個(gè)等位（拷貝）TGFBRI 基因中僅有1個(gè)被轉(zhuǎn)錄,；在對(duì)照組中，這一數(shù)字僅為1%~3%,。這種等位基因的不平衡,，導(dǎo)致攜帶者在其一生中TGFBR1基因的表達(dá)都會(huì)有輕微的降低，從而使得攜帶者罹患結(jié)腸直腸癌的風(fēng)險(xiǎn)增加,。Laura Valle估計(jì)該地區(qū)所有結(jié)腸直腸癌病例中，大約有10%與該遺傳風(fēng)險(xiǎn)因子有關(guān)聯(lián),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
