Abstract 4853: Constitutively decreased TGF-β signaling and risk for colorectal cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.4853-4853
• Main Authors: Pennison, Michael J., Bellam, Naresh, Zimmerman, Jacquelyn, Zeng, Qinghua, Sadim, Maureen, Kaklamani, Virginia, Li, Nengjun, Zhang, Kui, Stram, Daniel O., Pasche, Boris
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-4853

Background: Approximately one third of all colorectal cancers (CRC) are inherited, but less than 7% are attributable to known gene mutations. Germline variants within the TGF-β signaling pathway may account for colorectal cancer risk since TGF-β inhibits early tumor development through the activation of SMAD proteins. We have previously shown that Tgfbr1 haploinsufficiency is a potent modifier of colorectal cancer development in mice and humans. We have recently shown a significant association between a 3 SNP TGFBR1 haplotype and constitutively decreased TGFBR1 allelic expression, a phenotype found to occur frequently in patients with CRC. In this family-based study, we aimed at determining the association of TGFBR1 and SMAD7 with colorectal cancer risk. Methods: We studied 1,558 colorectal cancer cases and 2,640 healthy controls recruited by the Colorectal Cancer Family Registry (CCFR). We genotyped 14 TGFBR1 haplotype tagging SNPs as well as a SMAD7 SNP associated with CRC in prior GWA studies. SNPs were genotyped in all cases and controls using ABI's TaqMan platform, and associations were determined using logistical regression analysis (significance set at p