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Sci. Signal., 9 September 2008
Vol. 1, Issue 36, p. ec320
[DOI: 10.1126/scisignal.136ec320]

EDITORS' CHOICE

Medicine Quantity, Not Just Quality, Matters

Paula A. Kiberstis

Science, AAAS, Washington, DC 20005, USA

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Because 20 to 30% of cases occur in individuals with a family history of the disease, genetic factors are thought to be a substantial contributor to risk. Valle et al. now report that one of these factors is inherited variation in the expression level of a gene encoding a key signaling protein previously implicated in colorectal cancer pathogenesis. Within a Caucasian population in the United States, individuals with colorectal cancer are 5 to 10 times more likely than controls to show germline allele-specific expression of the TGFBR1 gene, which encodes the type I receptor for transforming growth factor–β. Allele-specific expression appears to result in a modest, but biologically meaningful, lifelong reduction in the expression of TGFBR1, which in turn confers an increased risk of colorectal cancer. Thus, it seems that the genetic contribution to disease risk includes not only mutations that abolish or modify the function of genes but also more subtle alterations that change the baseline expression levels of genes.

L. Valle, T. Serena-Acedo, S. Liyanarachchi, H. Hampel, I. Comeras, Z. Li, Q. Zeng, H.-T. Zhang, M. J. Pennison, M. Sadim, B. Pasche, S. M. Tanner, A. de la Chapelle, Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science 321, 1361-1365 (2008). [Abstract] [Full Text]

Citation: P. A. Kiberstis, Quantity, Not Just Quality, Matters. Sci. Signal. 1, ec320 (2008).


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