Título:
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LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk
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Autor/a:
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Salas, Lucas A.; Villanueva Belmonte, Cristina; Tajuddin, Salman Muhammad; Amaral, André F.S.; Fernández, Agustín F.; Moore, Lee E.; Carrato, Alfredo; Tardón, Adonina; Serra, Consol; García Closas, Reina; Basagaña Flores, Xavier; Rothman, Nathaniel; Silverman, Debra T.; Cantor, Kenneth P; Kogevinas, Manolis; Real, Francisco X.; Fraga, Mario F.; Malats i Riera, Núria
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Abstract:
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DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with β regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75(th) and 25(th) of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 μg/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects' high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted. |
Abstract:
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This study was partially supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (Contract NCI NO2-CP-11015); the Spanish Health Ministry (Fondo de Investigaciones Sanitarias–FIS, Instituto de Salud Carlos III, Spain 00/0745, ISIII-GO3/174, PI080533, PI051436, PI061614, PI09–02102, and PI11/00226) and the European Union (BMH4–98–3243); Red Temática de Investigación Cooperativa en Cáncer- RD12/0036/0050-RTICC; USA-NIH-RO1-CA089715; a postdoctoral fellowship awarded to AFSA from the Fundación Científica de la AECC; Fundació Marató TV3. The work was partially supported by the Association for International Cancer Research (AICR, #09–0780, including a PhD scholarship awarded to S.M.T.). The current analyses were supported by a Colciencias PhD Scholarship, Colombia (Grant: 529/2011 to L.A.S.). This work was also supported by grants from the Instituto de Salud Carlos III FEDER, (PI11/00226) |
Materia(s):
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-Granulòcits -ADN -- Metilació -Bufeta -- Càncer |
Derechos:
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© Taylor & Francis. This is an electronic version of an article published in Salas LA, Villanueva CM, Tajuddin SM, Amaral AF, Fernandez AF, Moore LE et al. LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk. Epigenetics. 2014 Nov; 9(11): 1532-9. Epigenetics is available online at: www.tandfonline.com (http://dx.doi.org/10.4161/15592294.2014.983377)
http://creativecommons.org/licenses/by-nc/3.0/ |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Taylor & Francis (Routledge)
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