Evaluation of a variant in the transcription factor 7‐like 2 (TCF7L2) gene and prostate cancer risk in a population‐based study

Abstract

Transcription factor 7-like 2 (TCF7L2) is a high mobility group -box containing protein that is a critical member of the Wnt/β-catenin signaling pathway. In addition to its recently recognized role in diabetes, aberrant TCF7L2 expression has been implicated in cancer through regulation of cell proliferation and apoptosis by c-MYC and cyclin D. It has been hypothesized that germline variants within the TCF7L2 gene previously associated with diabetes may affect cancer risk through the Wnt/ β-catenin signaling pathway. Specifically, the same risk allele of single nucleotide polymorphism (SNP) rs12255372 that is associated with diabetes (T allele) has recently been associated with an increased risk of breast cancer.Here, we investigated associations between rs12255372 and prostate cancer risk among 597 cases and 548 controls from a population-based study. We also evaluated prostate cancer progression/ recurrence and prostate-specific mortality among these cases under long-term surveillance. The risk allele was associated with cancer progression/recurrence after primary treatment [hazard ratio (HR) =1.48, 95% confidence interval (CI) =1.01-2.19), but this association was attenuated when the model was further adjusted for Gleason score and tumor stage. There were no associations between this SNP and the risk of developing disease or prostate cancer-specific mortality. Our findings suggest that this variant in the TCF7L2 gene may enhance tumor progression or metastasis, but it does not contribute significantly to tumor initiation. These findings are of clinical importance for identification of patients that may develop more aggressive/recurrent disease after primary treatment.

Association between TCF7L2 Gene Polymorphism and Cancer Risk: A Meta-Analysis

“…The finding was consistent with those from the individual studies by Folsom et al [5] and Machiela et al [12]. However, the other three included studies did not suggest any association [9]–[11]. In addition, we found positive association between rs7903146 polymorphism and breast cancer risk.…”

“…To date, many studies have been published investigating the association between TCF7L2 rs7903146 or rs12255372 (it is in high linkage disequilibrium with rs7903146) and several types of cancer, including breast cancer [4]–[8], prostate cancer [5], [9]–[12], colorectal cancer [5], [13]–[15], colon cancer [5], [16], lung cancer [5] and ovarian cancer [6]. However, the conclusions have been conflicting.…”

Genetic Susceptibility to Type 2 Diabetes Is Associated with Reduced Prostate Cancer Risk

“…Several small case-control studies of Caucasian men have shown modest (non-statistically significant) associations between the PPARG T2D risk allele and reduced PCa risk [37,38] . Candidate gene studies of TCF7L2 have shown either a modest (non-statistically significant) association between the T2D risk allele and decreased PCa risk [39] or associations close to the null [40] . Variation in JAZF has been implicated in both PCa and T2D [16] ; however, these associations do not appear to be due to a common causal SNP (i.e., the T2D-and PCa-associated SNPs are uncorrelated), suggesting that variation in JAZF may influence PCa and T2D through independent genetic mechanisms [17] .…”

Ausência de associação entre o genótipo CC do polimorfismo rs7903146 no gene TCF7L2 e artrite reumatoide

“…7,15 This same correlation has been verifi ed in other populations, including those of East Asia, Europe, West Africa and Scandinavia. [16][17][18][19] This genetic variant has also been associated with the risk of malignant neoplasms of prostate, 20 colon, 8 and breast. 9 There are still data that suggest involvement of the Wnt pathway in the infl ammatory response and in the physiopathology of chronic infl ammatory disease, which is the case for RA.…”