H2AX phosphorylation level in peripheral blood mononuclear cells as an event-free survival predictor for bladder cancer
Corresponding Author
Valentina Turinetto
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
Correspondence to: Department of Clinical Biological Sciences, University of Turin, Orbassano, Turin, Italy.
Correspondence to: Human Genetics Foundation (HuGeF), Turin, Italy.
Search for more papers by this authorCorresponding Author
Barbara Pardini
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Correspondence to: Department of Clinical Biological Sciences, University of Turin, Orbassano, Turin, Italy.
Correspondence to: Human Genetics Foundation (HuGeF), Turin, Italy.
Search for more papers by this authorAlessandra Allione
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorGiovanni Fiorito
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorClara Viberti
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorSimonetta Guarrera
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorAlessia Russo
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorSilvia Anglesio
Department of Oncology, Radiation Oncology Unit, S. Luigi Hospital, University of Turin, Orbassano, Italy
Search for more papers by this authorMaria Grazia Ruo Redda
Department of Oncology, Radiation Oncology Unit, S. Luigi Hospital, University of Turin, Orbassano, Italy
Search for more papers by this authorGiovanni Casetta
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorGiuseppina Cucchiarale
Department of Urology, Clinica Cellini, Turin, Italy
Search for more papers by this authorPaolo Destefanis
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorMarco Oderda
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorPaolo Gontero
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorLuigi Rolle
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorBruno Frea
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorPaolo Vineis
Human Genetics Foundation (HuGeF), Turin, Italy
MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom
Search for more papers by this authorCarlotta Sacerdote
Center for Cancer Prevention (CPO-Piemonte), Turin, Italy
Search for more papers by this authorClaudia Giachino
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
Search for more papers by this authorGiuseppe Matullo
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorCorresponding Author
Valentina Turinetto
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
Correspondence to: Department of Clinical Biological Sciences, University of Turin, Orbassano, Turin, Italy.
Correspondence to: Human Genetics Foundation (HuGeF), Turin, Italy.
Search for more papers by this authorCorresponding Author
Barbara Pardini
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Correspondence to: Department of Clinical Biological Sciences, University of Turin, Orbassano, Turin, Italy.
Correspondence to: Human Genetics Foundation (HuGeF), Turin, Italy.
Search for more papers by this authorAlessandra Allione
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorGiovanni Fiorito
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorClara Viberti
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorSimonetta Guarrera
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorAlessia Russo
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorSilvia Anglesio
Department of Oncology, Radiation Oncology Unit, S. Luigi Hospital, University of Turin, Orbassano, Italy
Search for more papers by this authorMaria Grazia Ruo Redda
Department of Oncology, Radiation Oncology Unit, S. Luigi Hospital, University of Turin, Orbassano, Italy
Search for more papers by this authorGiovanni Casetta
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorGiuseppina Cucchiarale
Department of Urology, Clinica Cellini, Turin, Italy
Search for more papers by this authorPaolo Destefanis
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorMarco Oderda
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorPaolo Gontero
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorLuigi Rolle
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorBruno Frea
Department of Urology, Città della Salute e della Scienza, Turin, Italy
Search for more papers by this authorPaolo Vineis
Human Genetics Foundation (HuGeF), Turin, Italy
MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom
Search for more papers by this authorCarlotta Sacerdote
Center for Cancer Prevention (CPO-Piemonte), Turin, Italy
Search for more papers by this authorClaudia Giachino
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
Search for more papers by this authorGiuseppe Matullo
Human Genetics Foundation (HuGeF), Turin, Italy
Department of Medical Sciences, University of Turin, Turin, Italy
Search for more papers by this authorAbstract
Bladder cancer (BC) has a typical aetiology characterized by a multistep carcinogenesis due to environmental exposures, genetic susceptibility, and their interaction. Several lines of evidence suggest that DNA repair plays a role in the development and progression of BC. In particular, the study of individual susceptibility to DNA double strand breaks (DSBs) may provide valuable information on BC risk, and help to identify those patients at high-risk of either recurrence or progression of the disease, possibly personalizing both surveillance and treatment. Among the different DSB markers, the most well characterized is phosphorylation of the histone H2AX (γ-H2AX). We assessed any potential role of γ-H2AX as a molecular biomarker in a case-control study (146 cases and 146 controls) to identify individuals with increased BC risk and at high-risk of disease recurrence or progression. We investigated γ-H2AX levels in peripheral blood mononuclear cells before and after their exposure to ionizing radiation (IR). We did not find any significant difference among cases and controls. However, we observed a significant association between γ-H2AX basal levels and risk of disease recurrence or progression. In particular, both BC patients as a whole and the subgroup of non-muscle invasive BC (NMIBC) with high basal H2AX phosphorylation levels had a decreased risk of recurrence or progression (for all BC HR 0.70, 95%CI 0.52–0.94, P = 0.02; for NMIBC HR 0.68, 95%CI 0.50–0.92, P = 0.01), suggesting a protective effect of basal DSB signaling. Our data suggest that γ-H2AX can be considered as a potential molecular biomarker to identify patients with a higher risk of BC recurrence. © 2015 Wiley Periodicals, Inc.
Supporting Information
Additional supporting information may be found in the online version of this article at the publisher's web-site.
| Filename | Description |
|---|---|
| mc22431-sup-0001-SuppTable-S1.doc37.5 KB | Supplementary Table I. H2AX phosphorylation and dephosphorylation in PBMCs from BC cases and healthy controls stratified for smoking habit (Wilcoxon test) (median values). |
| mc22431-sup-0002-Supptable-S2.docx17.7 KB | Supplementary Table II. H2AX phosphorylation H2AX phosphorylation assay affecting Event Free Survival (EFS) in BC cases and NMIBC stratified according to the optimal cut-off value based on the AUC. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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