The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors.
In summary, the marginal association of the TCF7L2 SNP with CRC might be due to chance, but warrants further laboratory and epidemiological investigation.
The results indicated that the TCF7L2rs11196172 polymorphism increases the risk of CRC independently, with no evidence of an interaction with diabetes or obesity.
A further analysis revealed gender-specific effects: the TCF7L2_rs7903146_T allele was associated with an increased risk of CRC in women (P(trend) = 0.003) but not in men (P(interaction) = 0.06); the LTA_rs1041981_A allele was associated with a decreased risk for CRC in women (P(trend) = 0.02), with an opposite effect in men (P(trend) = 0.05; P(interaction) = 0.002); the CDKAL1_rs7754840_C allele was associated with a decreased risk for CRC in men (P(trend) = 0.03), with no effect in women (P(interaction) = 0.03).
Of interest, we described a frequent TCF-4 frameshift mutation in mismatch-repair deficient colorectal cancers (MSI-H cancers) that leads to the selective loss of TCF-4 isoforms with CtBP binding abilities.
Mutations of BAX (G8) and TCF-4 (A9), which are common in MSI-positive colorectal cancer, occurred at rates of 22.7 and 0%, respectively, which suggests that the MSI target gene may differ between endometrial and colorectal cancers.
The single nucleotide polymorphism (SNP) rs6983267 on chromosome 8q24 is a CRC susceptibility locus that affects binding activity of transcription factor 7 like-2 (TCF7L2) to CTNNB1, thereby altering expression of target oncogenes, including MYC.
The results demonstrate that patients with the T/T genotype for the rs12255372 polymorphism of the TCF7L2 gene present an increased colorectal cancer risk (OR=2.64, P=0.0236).
T-cell factor-4 frameshift mutations occur frequently in human microsatellite instability-high colorectal carcinomas but do not contribute to carcinogenesis.
The results showed that TCF7L2 polymorphism was associated with breast cancer (Homogeneous model: OR=1.17, 95%CI=1.02-1.35, I (2) =21.8%, p for heterogeneity=0.276; Heterogeneous model: OR=1.11, 95%CI=1.03-1.20, I (2) =0.0%, p for heterogeneity=0.543), prostate cancer (Homogeneous model: OR=0.89, 95%CI=0.84-0.96, I (2) =0.0%, p for heterogeneity=0.640; Heterogeneous model: OR=0.89, 95%CI=0.84-0.95, I (2) =0.0%, p for heterogeneity=0.871), and colon cancer (Heterogeneous model: OR=1.15, 95%CI=1.01-1.31, I (2) =0.0%, p for heterogeneity=0.658), but not with colorectal cancer, lung cancer, and ovarian cancer.
Using HT-29 CRC cell lines having inducible wild-type APC (wt-APC) or transfected dominant-negative TCF-4, we show that wt-APC down-regulates survivin expression via APC/beta-catenin/TCF-4 signaling.
We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown.
The overexpression of some proproliferative and antiapoptotic genes, such as survivin, telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK), and regulatory factors c-MYB and Tcf-4, has been implicated in the development and progression of several human malignancies including CRC.