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Abstract 1153: TGFβR1 germline variant Int7G24A but not TGFβR1*6 increases risk for colon cancer

Transforming growth factor beta (TGF-β) regulates many processes associated with tumor initiation and progression including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. The TGF-β signal is transduced by a membrane-bound serine-threonine kinase receptor complex including TGF-β type I and type II receptors. Germline variations in the gene for transforming growth factor beta receptor 1(TGFβR1), a G-to-A single nucleotide polymorphism within intron 7 of the TGFβR1 gene called Int7G24A, and TGFβR1*6A, a nine base pair deletion that occurs in the coding region in exon 1 of the TGFβR1 gene, have been associated with progression and/or initiation of cancers of the kidney and bladder, lung, and breast; however, the association of TGFβR1*6A and Int7G24A with colon cancer is controversial. Approximately 141,000 new cases of colorectal cancer (CRC) will be diagnosed in the US during 2012 and there will be more than 69,000 CRC related deaths. Detection of CRC at early stages is the key to survival, hence we sought to determine a possible association of TGFβR1*6A and Int7G24A with CRC risk. These two germline variants in TGFβR1 were analyzed by capillary electrophoresis in DNA extracted from FFPE archived specimens of normal tissues from 253 patients with colorectal neoplasms and 219 patients who never developed any form of cancer. We found that 46.5% of patients with CIS (stage 0), 46.7% of patients with invasive CRC (Stages I & II) and 46.7% of patients with metastatic CRC (Stages III & IV) were carriers of Int7G24A, compared to 24.7% of patients without any cancer, and this difference was highly significant (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1153. doi:1538-7445.AM2012-1153