Independent Replication of Published Germline Polymorphisms Associated with Urinary Bladder Cancer Prognosis and Treatment Response

Abstract

Background:Many studies investigated the prognostic or predictive relevance of single nucleotide polymorphisms (SNPs) in biologically plausible genes in urinary bladder cancer (UBC) patients. Most published SNP associations have never been replicated in independent patient series.Objective:To independently replicate all previously reported associations between germline SNPs and disease prognosis or treatment response in UBC.Methods:A Pubmed search was performed to identify studies published by July 1, 2014 reporting on germline SNP associations with UBC prognosis or treatment response. For the replication series, consisting of 1,284 non-muscle-invasive bladder cancer (NMIBC) and 275 muscle-invasive or metastatic bladder cancer (MIBC) patients recruited through the Netherlands Cancer Registry, detailed clinical data were retrieved from medical charts. Patients were genotyped using a genome-wide SNP array. SNP association with recurrence-free, progression-free, and overall survival (OS) within specific patient and treatment strata was tested using Cox regression analyses.Results:For only six of the 114 evaluated SNPs, the association with either UBC prognosis or treatment response was replicated at the p < 0.05 level: rs1799793 (ERCC2) and rs187238 (IL18) for BCG recurrence; rs6678136 (RGS4) and rs11585883 (RGS5) for NMIBC progression; rs12035879 (RGS5) and rs2075786 (TERT) for MIBC OS.Conclusions:Non-replicated genetic associations in the literature require cautious interpretation. This single replication does not provide definitive proof of association for the six SNPs, and non-replication of other SNPs may result from population-specific effects or the retrospective patient enrollment.

A systematic review and meta-analysis of the association between HOTAIR polymorphisms and susceptibility to breast cancer

“…The development of breast cancer is very complicated, and includes environmental and genetic elements. As one of the genetic variants, single nucleotide polymorphisms (SNPs) are widely used to predict the disease risk, prognosis, and 2 Arch Med Sci clinical outcome [2,3]. Accumulative investigations have found that SNPs in tumor oncogenes or suppressor genes could play a vital role in breast cancer genetic susceptibility [4][5][6][7][8][9][10][11][12][13].…”

HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children

“…As an oncogene, HOTAIR lncRNA is involved in the initiation and progression of cancer and also plays a key role in promoting malignancy, suggesting it might be a novel prognostic biomarker and a potential target in cancer therapy . As a type of genetic variant, SNP is widely used in the prediction of disease risk, clinical outcome, and prognosis . It is interesting to note that multiple SNPs across the entire HOTAIR gene have been demonstrated to influence the cancer risk .…”

“…29,30 As a type of genetic variant, SNP is widely used in the prediction of disease risk, 31 clinical outcome, 32 and prognosis. 33 It is interesting to note that multiple SNPs across the entire HOTAIR gene have been demonstrated to influence the cancer risk. [34][35][36][37] To our knowledge to date, the association between HOTAIR gene polymorphisms and neuroblastoma susceptibility has not been reported.…”

The role of molecular genetic alterations in sensitivity of the adjuvant intravesical therapy for non-muscle invasive bladder cancer

“…Генотип TT -чувствительность к БЦЖ TT genotype -sensitivity to BCG [34] обнаружена ассоциация генотипа СС полиморфизма 844T / C в промоторе FASL с гиперэкспрессией этого гена и уменьшением безрецидивного периода после ТУР и БЦЖ-терапии [31]. В различных популяциях показана ассоциация генотипа GG полиморфизма rs187 238 в гене IL18 с эффективностью БЦЖ-терапии [30]. По данным метаанализа, включающего 113 оригинальных работ, показана ассоциация с эффективностью БЦЖ-терапии гомозиготных генотипов полиморфизмов в генах IL6, IL8, IL2RA, IL17RA, TRAILR1, TNFA, NFKB, IFNG, TGFB (см.…”

“…Обзоры БЦЖ-терапии [32]. В метаанализе с рецидивом после БЦЖ-терапии также был ассоциирован генотип ТТ полиморфизма rs1 799 793 в гене ERCC2, участвующего в эксцизионной репарации [30]. Результаты исследования эпигенетического репрограммирования моноцитов в ответ на инстилляцию вакцины БЦЖ показали, что с рецидивом ассоциирован аллель С полиморфизма rs3 759 601 в гене ATG2B, участвующего в аутофагии [28].…”