Germline Allele-Specific Expression of <i>TGFBR1</i> Confers an Increased Risk of Colorectal Cancer

DOI Web Site 被引用文献3件
  • Laura Valle
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Tarsicio Serena-Acedo
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Sandya Liyanarachchi
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Heather Hampel
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Ilene Comeras
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Zhongyuan Li
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Qinghua Zeng
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Hong-Tao Zhang
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Michael J. Pennison
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Maureen Sadim
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Boris Pasche
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Stephan M. Tanner
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  • Albert de la Chapelle
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.

抄録

<jats:p> Much of the genetic predisposition to colorectal cancer (CRC) in humans is unexplained. Studying a Caucasian-dominated population in the United States, we showed that germline allele-specific expression (ASE) of the gene encoding transforming growth factor–β (TGF-β) type I receptor, <jats:italic>TGFBR1</jats:italic> , 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 <jats:italic>TGFBR1</jats:italic> expression alters SMAD-mediated TGF-β signaling. Two major <jats:italic>TGFBR1</jats:italic> 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 will probably show ethnic differences. </jats:p>

収録刊行物

  • Science

    Science 321 (5894), 1361-1365, 2008-09-05

    American Association for the Advancement of Science (AAAS)

被引用文献 (3)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ