Dataset Information

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

ABSTRACT: TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR?=?0.25 [0.18-0.37], p?=?0.0001) or for pT1 tumours alone (OR?=?0.47 [0.28-0.79], p?=?0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR?=?0.56 [0.23-1.36] (p?=?0.12) and OR?=?0.99 [0.37-2.7] (p?=?0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.

SUBMITTER: Neuzillet Y

PROVIDER: S-EPMC3521761 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

Neuzillet Yann Y Paoletti Xavier X Ouerhani Slah S Mongiat-Artus Pierre P Soliman Hany H de The Hugues H Sibony Mathilde M Denoux Yves Y Molinie Vincent V Herault Aurélie A Lepage May-Linda ML Maille Pascale P Renou Audrey A Vordos Dimitri D Abbou Claude-Clément CC Bakkar Ashraf A Asselain Bernard B Kourda Nadia N El Gaaied Amel A Leroy Karen K Laplanche Agnès A Benhamou Simone S Lebret Thierry T Allory Yves Y Radvanyi François F

PloS one 20121213 12

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additiona ...[more]

PMID: 23272046

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Project description:BACKGROUND: Physical activity may protect against bladder cancer through several biologic pathways, such as enhanced immune function and decreased chronic inflammation. Physical activity may also indirectly prevent bladder cancer by reducing obesity. A sizeable number of epidemiologic studies have examined the association between physical activity and bladder cancer, but the available evidence has not yet been formally summarised using meta-analysis. METHODS: We performed a systematic literature review and meta-analysis of English-language studies published from January 1975 through November 2013. We followed the PRISMA guidelines and used a random effects model to estimate the summary risk estimates for the association between physical activity and bladder cancer. RESULTS: A total of 15 studies with 5,402,369 subjects and 27,784 bladder cancer cases were included. High vs low levels of physical activity were related to decreased bladder cancer risk (summary relative risk (RR)=0.85, 95% confidence interval (CI)=0.74-0.98; I(2)=83%; P-value for heterogeneity across all studies<0.001). Results were similar for cohort studies (RR=0.89, 95% CI=0.80-1.00; I(2)=64%) and case-control studies (RR=0.71, 95% CI=0.43-1.16; I(2)=87%; P-value for difference=0.108) and they were comparable for women (RR=0.83, 95% CI=0.73-0.94; I(2)=0%) and men (RR=0.92, 95% CI=0.82-1.05; I(2)=67; P-value for difference=0.657). Findings were also comparable for recreational (RR=0.81, 95% CI=0.66-0.99; I(2)=77%) and occupational physical activity (RR=0.90, 95% CI=0.76-1.0; I(2)=76%; P-value for difference=0.374), and they were largely consistent for moderate (RR=0.85, 95% CI=0.75-0.98; I(2)=76%) and vigorous activity (RR=0.80, 95% CI=0.64-1.00;I(2)=87%; P-value for difference=0.535). CONCLUSIONS: Physical activity is associated with decreased risk of bladder cancer. Further studies are required to assess the relations of intensity, frequency, duration, and timing in life of physical activity to bladder cancer risk.

Project description:Fifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic procedure than cystoscopy.To address these issues, we developed a mutation assay for the simultaneous detection of 19 possible mutations in the HRAS, KRAS, and NRAS genes. With this assay and mutation assays for the FGFR3 and PIK3CA oncogenes, we screened primary bladder tumors of 257 patients and 184 recurrences from 54 patients. Additionally, in primary tumors p53 expression was obtained by immunohistochemistry. Of primary tumors 64% were mutant for FGFR3, 11% for RAS, 24% for PIK3CA, and 26% for p53. FGFR3 mutations were mutually exclusive with RAS mutations (p?=?0.001) and co-occurred with PIK3CA mutations (p?=?0.016). P53 overexpression was mutually exclusive with PIK3CA and FGFR3 mutations (p?0.029). Mutations in the RAS and PIK3CA genes were not predictors for recurrence-free, progression-free and disease-specific survival. In patients presenting with NMI-BC grade 3 and MI-BC, 33 and 36% of the primary tumors were mutant. In patients with low-grade NMI-BC, 88% of the primary tumors carried a mutation and 88% of the recurrences were mutant.The mutation assays present a companion diagnostic to define patients for targeted therapies. In addition, the assays are a potential biomarker to detect recurrences during surveillance. We showed that 88% of patients presenting with low-grade NMI-BC are eligible for such a follow-up. This may contribute to a reduction in the number of cystoscopical examinations.

Dataset Information

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

Publications

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

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