Publication Date:
2008-08-16
Description:
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-beta (TGF-beta) 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 TGF-beta 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 will probably show ethnic differences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672914/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valle, Laura -- Serena-Acedo, Tarsicio -- Liyanarachchi, Sandya -- Hampel, Heather -- Comeras, Ilene -- Li, Zhongyuan -- Zeng, Qinghua -- Zhang, Hong-Tao -- Pennison, Michael J -- Sadim, Maureen -- Pasche, Boris -- Tanner, Stephan M -- de la Chapelle, Albert -- CA108741/CA/NCI NIH HHS/ -- CA112520/CA/NCI NIH HHS/ -- CA16058/CA/NCI NIH HHS/ -- CA67941/CA/NCI NIH HHS/ -- R01 CA108741/CA/NCI NIH HHS/ -- R01 CA108741-01A2/CA/NCI NIH HHS/ -- R01 CA112520/CA/NCI NIH HHS/ -- R01 CA112520-01A1/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1361-5. doi: 10.1126/science.1159397. Epub 2008 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18703712" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions
;
Adult
;
Aged
;
Aged, 80 and over
;
Alleles
;
Cell Line
;
Colorectal Neoplasms/*genetics
;
Female
;
*Gene Expression
;
*Genetic Predisposition to Disease
;
Haplotypes
;
Heterozygote
;
Humans
;
Linkage Disequilibrium
;
Male
;
Middle Aged
;
Polymorphism, Single Nucleotide
;
Protein-Serine-Threonine Kinases/*genetics
;
Quantitative Trait, Heritable
;
Receptors, Transforming Growth Factor beta/*genetics
;
Risk Factors
;
Signal Transduction
;
Smad3 Protein/metabolism
;
Transforming Growth Factor beta/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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