study The average age at diagnosis of the patients with sporadic

study. The average age at diagnosis of the patients with sporadic colorectal cancer in that study was 69 while the median age at diagnosis in our study was 60. Also, the proportion of Caucasians was more than 10% lower in the Guda study (71%) than in our study (83%). However, the main difference between these two studies is the tissue from which DNA and RNA were extracted. In both our original report[14]

and in this study we used lymphoblastoid cell lines and peripheral blood lymphocytes whereas Guda et al. extracted DNA and RNA from the normal-appearing mucosa layer of the colon from patients with sporadic colorectal cancer[15]. The authors assumed that if TGFBR1 ASE were a driver of colorectal cancer, the lower expression of one TGFBR1 allele should likely also be evidenced in colon SN-38 ic50 epithelial cells from affected individuals. While we agree with this reasoning, it possible that the TGFBR1 allelic expression ratio in lymphoblastoid cell lines is not the same as in normal appearing colonic epithelium. We have previously shown that TGFBR1*6A, one of the SNPs previously associated with the TGFBR1 ASE phenotype[14], is somatically acquired in this website the normal appearing colonic epithelium of a small proportion of patients with colorectal cancer[17]. This provides support for

the notion that either somatically-acquired mutations or epigenetic changes may affect the TGFBR1 gene in the normal appearing colonic epithelium and may GW2580 mouse therefore affect determination of the TGFBR1 ASE phenotype. Several Miconazole recent studies have demonstrated that genetic alterations within the stroma may have a potent effect on cancer progression[18]. Hence, another potential explanation for these differences is altered stromal TGF-β signaling, which is emerging as a potent modifier of cancer susceptibility[19]. Identification of the TGFBR1 ASE phenotype in African American patients suggests that this phenotype may not be exclusively

found in Caucasians. Additional studies in various ethnic groups are warranted. In summary our results confirm the high frequency of the TGFBR1 ASE phenotype among patients with colorectal cancer and suggest a central role of the TGFBR1 locus in the etiology of this disease. Funding Supported by grants from the UAB startup funds and grants CA112520, CA108741, CA137000 and 5P60AR048098 from the NIH. Presented in part Abstract # 95, American Association for Cancer Research 100th Annual Meeting 2009 in Denver, CO References 1. Kemp Z, Thirlwell C, Sieber O, Silver A, Tomlinson I: An update on the genetics of colorectal cancer. Human Molecular Genetics 2004, 13:R177-R185.PubMedCrossRef 2. de la Chapelle A: Genetic predisposition to colorectal cancer. Nat Rev Cancer 2004, 4:769–780.PubMedCrossRef 3. Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, et al.: Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.

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