title: Genetic variants of the Wnt signaling pathway as predictors of aggressive disease and reclassification in men with early stage prostate cancer on active surveillance.
abstract: Little is known about the genetic predictors of prostate cancer aggressiveness and reclassification in men with localized prostate cancer undergoing active surveillance. The Wnt signaling pathway is important for prostate cancer development and progression. Identifying genetic variants associated with prostate cancer aggressiveness and reclassification may have a potential role in the management of localized patients. In this study, we used a three-phase design. In phases I and II prostate cancer patient cohort, 578 single nucleotide polymorphisms (SNPs) from 45 genes of the Wnt signaling pathway were analyzed in 1762 localized prostate cancer patients. Twelve SNPs from four regions were significantly associated with aggressive disease, among which, three linked SNPs in CSNK1A1 at 5q32 (represented by rs752822) may differentiate GS 4+3 from GS 3+4 patients (OR = 1.44, 95% CI = 1.12-1.87, P = 4.76×10(-3)). In phase III active surveillance (AS) cohort, genotyping of rs752822 (candidate from phases I and II) and previously identified rs2735839 were determined in 494 GS ≤7 patients. We found a significant association between rs2735839 and prostate cancer reclassification in the AS cohort (AG + AA versus GG, HR = 1.59, 95% CI = 1.11-2.28, P = 0.012) and a suggestive association of rs752822. Jointly, rs752822 and rs2735839 showed good potentials in risk-stratifying GS 7 patients and predicting disease reclassification (OR = 2.71, 95% CI = 1.62-4.51, P = 1×10(-4) in phase II; HR = 1.89, 95% CI = 1.13-3.18, P = 0.016 in phase III). In summary, rs752822 and rs2735839 may assist in risk-stratifying GS 7 patients and predict prostate cancer reclassification. The significant associations were independent from GS, T stage and PSA levels at baseline.
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Xiang
authors: X
authors: Shu
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yuanqing
authors: Y
authors: Ye
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Jian
authors: J
authors: Gu
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Yonggang
authors: Y
authors: He
authors: Department of Urology and.
authors: John W
authors: JW
authors: Davis
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Timothy C
authors: TC
authors: Thompson
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Christopher J
authors: CJ
authors: Logothetis
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Jeri
authors: J
authors: Kim
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Xifeng
authors: X
authors: Wu
mesh_terms: D000368:Aged; D047390:Casein Kinase II / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II