Genetic Interaction Analysis of TCF7L2 for Biochemical Recurrence after Radical Prostatectomy in Localized Prostate Cancer

Backgroud: Accumulated evidence has demonstrated a significant role of the Wnt pathway in human prostate cancer. We hypothesize that genetic variants in the Wnt pathway effector, Transcription factor 7-like 2 (TCF7L2), may influence clinical outcomes in prostate cancer. Methods: We comprehensively selected 12 tagged single-nucleotide polymorphisms (SNPs) to capture majority of common variants across TCF7L2, and genotyped in 458 localized prostate cancer patients treated with radical prostatectomy (RP). Kaplan-Meier analysis, Cox proportional hazard model, and survival tree analyses were performed to identify significant SNPs that correlated with biochemical recurrence (BCR) after surgery. Results: A higher-order SNP-SNP interaction profile consisting of TCF7L2 rs7094463, rs10749127, and rs11196224 was significantly associated with BCR (P(trend) = 0.001). After adjusting for possible confounders, the genetic profile remained significant (P(trend) = 0.007). None of the studied SNPs were individually associated with BCR. Conclusions: Our results support a genetic interaction in the TCF7L2 SNPs as a predictor of disease recurrence after curative RP in localized prostate cancer patients.