RESUMEN
BACKGROUND: Patients with non-muscle invasive bladder cancer (NMIBC) are at a high risk of tumor recurrence. It has not been previously investigated if adherence to cancer prevention recommendations lowers the risk of recurrence. OBJECTIVES: We examined whether the standardized lifestyle score measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with the risk of recurrence and progression among patients with NMIBC. METHODS: The study population included patients diagnosed with primary NMIBC between 2014 and 2017 from the prospective cohort UroLife. Lifestyle was assessed at baseline (n = 979; reflecting the prediagnosis period) and 3-mo postdiagnosis (n = 885). The standardized 2018 WCRF/AICR score was constructed based on recommendations for body weight, physical activity, diet, and alcohol intake. We computed multivariable-adjusted HRs and 95% CIs using Cox proportional hazard regression models. RESULTS: During a median follow-up time of 3.7 y, 320 patients developed ≥1 recurrence(s) and 49 experienced progression. Patients in the highest compared with the lowest tertile of postdiagnosis WCRF/AICR scores had a lower risk of first bladder cancer recurrence (HR: 0.74; 95% CI: 0.56, 0.98). No associations were observed for multiple recurrences (HR: 0.90; 95% CI: 0.70, 1.15) or for the baseline score with either first (HR: 1.07; 95% CI: 0.82, 1.40) or multiple recurrences (HR: 1.04; 95% CI: 0.82, 1.31). Improving lifestyle after diagnosis (per 1-point increase) was not significantly associated with the risk of first or multiple recurrence(s) (HR: 0.87; 95% CI: 0.74, 1.02; HR: 0.93; 95% CI: 0.80, 1.08, respectively). No associations were observed for bladder cancer progression, but the power was limited. CONCLUSIONS: Better adherence to the WCRF/AICR cancer prevention recommendations 3 mo after NMIBC diagnosis, but not before diagnosis, is associated with a decreased risk of first bladder cancer recurrence. More studies evaluating postdiagnosis lifestyles are needed to provide solid support for lifestyle recommendations for cancer survivors.
Asunto(s)
Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Estados Unidos , Estudios Prospectivos , Estudios de Cohortes , Recurrencia Local de Neoplasia , Estilo de Vida , Factores de RiesgoRESUMEN
Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 × 10-7). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.
Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/genética , Cromosomas Humanos Par 16/genética , Labio Leporino/genética , Fisura del Paladar/genética , Animales , Bélgica , Cromosomas Humanos Par 10/genética , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Ratones , Ratones Noqueados , Países Bajos , Factores de Riesgo , Pez CebraRESUMEN
INTRODUCTION: Patients with non-muscle-invasive bladder cancer (NMIBC) have a good survival but are at high risk for tumour recurrence and disease progression. It is important to identify lifestyle habits that may reduce the risk of recurrence and progression and improve health-related quality of life (HRQOL). This paper describes the rationale and design of the UroLife study. The main aim of this study is to evaluate whether lifestyle habits are related to prognosis and HRQOL in patients with NMIBC. METHODS AND ANALYSIS: The UroLife study is a multicentre prospective cohort study among more than 1100 newly diagnosed patients with NMIBC recruited from 22 hospitals in the Netherlands. At 6 weeks and 3, 15 and 51 months after diagnosis, participants fill out a general questionnaire, and questionnaires about their lifestyle habits and HRQOL. At 3, 15 and 51 months after diagnosis, information about fluid intake and micturition is collected with a 4-day diary. At 3 and 15 months after diagnosis, patients donate blood samples for DNA extraction and (dietary) biomarker analysis. Tumour samples are collected from all patients with T1 disease to assess molecular subtypes. Information about disease characteristics and therapy for the primary tumour and subsequent recurrences is collected from the medical records by the Netherlands Cancer Registry. Statistical analyses will be adjusted for age, gender, tumour characteristics and other known confounders. ETHICS AND DISSEMINATION: The study protocol has been approved by the Committee for Human Research region Arnhem-Nijmegen (CMO 2013-494). Patients who agree to participate in the study provide written informed consent. The findings from our study will be disseminated through peer-reviewed scientific journals and presentations at (inter)national scientific meetings. Patients will be informed about the progress and results of this study through biannual newsletters and through the website of the study and of the bladder cancer patient association.
Asunto(s)
Estilo de Vida Saludable , Recurrencia Local de Neoplasia , Calidad de Vida , Neoplasias de la Vejiga Urinaria/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carotenoides/sangre , Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Países Bajos , Pronóstico , Estudios Prospectivos , Proyectos de Investigación , Encuestas y Cuestionarios , Tocoferoles/sangre , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Adulto JovenRESUMEN
Epidemiological studies show that type 2 diabetes (T2D) is inversely associated with intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA). Although adiposity has not been considered a risk factor for IA, there have been inconsistent reports relating adiposity to AAA risk. We assessed whether these observations have a genetic, causal basis. To this end, we extracted genotypes of validated single-nucleotide polymorphisms associated with T2D (n=65), body mass index (BMI) (n=97) and waist-hip ratio adjusted for BMI (WHRadjBMI) (n=47) from genotype data collected in 717 IA cases and 1988 controls, and in 818 AAA cases and 3004 controls, all of Dutch descent. For each of these three traits, we computed genetic risk scores (GRS) for each individual in these case-control data sets by summing the number of risk alleles weighted by their published effect size, and tested whether these GRS were associated with risk of aneurysm. We divided the cohorts into GRS quartiles, and compared IA and AAA risk in the highest with the lowest GRS quartile using logistic regression. We found no evidence for association in IA or AAA risk between top and bottom quartiles for the genetic risk scores for T2D, BMI and WHRadjBMI. However, additional Mendelian randomization analyses suggested a trend to potentially causal associations between BMI and WHRadjBMI and risk of AAA. Overall, our results do not support epidemiological observations relating T2D to aneurysm risk, but may indicate a potential role of adiposity in AAA that requires further investigation.