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. 2015 Feb 5;12(3):243-7.
doi: 10.7150/ijms.10953. eCollection 2015.

Genetic interaction analysis of TCF7L2 for biochemical recurrence after radical prostatectomy in localized prostate cancer

Chien-Shu Chen  1 , Chao-Yuan Huang  2 , Shu-Pin Huang  3 , Victor C Lin  4 , Chia-Cheng Yu  5 , Ta-Yuan Chang  6 , Bo-Ying Bao  7
Affiliations

Genetic interaction analysis of TCF7L2 for biochemical recurrence after radical prostatectomy in localized prostate cancer

Chien-Shu Chen et al. Int J Med Sci. .

Abstract

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.

Keywords: TCF7L2; Wnt pathway; biochemical recurrence; prostate cancer; radical prostatectomy; single-nucleotide polymorphism.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Higher order SNP-SNP interactions among TCF7L2 polymorphisms for BCR in localized prostate cancer patients. (A) Survival tree analysis identifies the interactions among the three polymorphisms. (B) Kaplan-Meier curves of BCR-free survival based on the survival tree analysis. Numbers in parentheses indicate the number of patients.
Figure 2
Figure 2
Expanded view of the ENCODE data for the LD blocks containing the three interacting SNPs. ENCODE data showed evidence of promoter/enhancer elements coinciding with the variants linked with the three interacting SNPs, rs7094463, rs10749127, and rs11196224. The H3K4Me1, H3K4Me3, and H3K27Ac tracks show the genome-wide levels of enrichment of the mono-methylation of lysine 4, tri-methylation of lysine 4, and acetylation of lysine 27 of the H3 histone protein, as determined by the ChIP-seq assays. These levels are thought to be associated with enhancer and promoter regions. Chromatin State Segmentation track displays chromatin state segmentations by integrating ChIP-seq data using a Hidden Markov Model for eight different cell types. The chromatin state regions predicted for promoters and enhancers are highlighted. DNase clusters track shows DNase hypersensitivity areas. Tnx Factor track shows regions of transcription factor binding of DNA, as assayed by ChIP-seq experiments.
See this image and copyright information in PMC

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