Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study

a case-control study

Lee E. Moore, Ruth M. Pfeiffer, Cristina Poscablo, Francisco X. Real, Manolis Kogevinas, Debra Silverman, Reina García-Closas, Stephen Chanock, Adonina Tardón, Consol Serra, Alfredo Carrato, Mustafa Dosemeci, Montserrat García-Closas, Manel Esteller, Mario Fraga, Nathaniel Rothman, Núria Malats

Research output: Contribution to journalArticle

Abstract

Background: DNA hypomethylation has been suggested to cause genomic instability and increase cancer risk. We aimed to test the hypothesis that DNA hypomethylation is associated with increased risk of bladder cancer. Methods: We measured cytosine methylation (5-mC) content in genomic DNA from blood cells from patients with bladder cancer enrolled in a large case-control study in Spain between Jan 1, 1998, and Dec 31, 2001. Cases were men and women with newly diagnosed and histologically confirmed urothelial carcinoma of the bladder. Controls were selected from patients admitted to the same hospital for diseases or conditions unrelated to smoking or other known risk factors for bladder cancer. Controls were individually matched to cases on age (within 5 years), sex, race, and area of hospital referral. 5-mC content was measured in leucocyte DNA by use of a combination of high-performance capillary electrophoresis, Hpa II digestion, and densitometry. Data on demographics, 34 polymorphisms in nine folate metabolism genes, and nutritional intake of six B vitamins (including folate), alcohol, and smoking were assessed as potential confounders. Relative 5-mC content was expressed as a percentage (%5-mC) with respect to the total cytosine content (the sum of methylated and non-methylated cytosines). The primary endpoint was median %5-mC DNA content. Findings: %5-mC was measured in leucocyte DNA from 775 cases and 397 controls. Median %5-mC DNA was significantly lower in cases (3·03% [IQR 2·17-3·56]) than in controls (3·19% [2·46-3·68], p=0·0002). All participants were subsequently categorised into quartiles by %5-mC content in controls. When the highest quartile of %5-mC content was used as the reference category (Q4), the following adjusted odds ratios (OR) and 95% CI were recorded for decreasing methylation quartiles: OR(Q3) 2·05 (95% CI 1·37-3·06); OR(Q2) 1·62 (1·07-2·44); and OR(Q1) 2·67 (1·77-4·03), p for trend

Original languageEnglish (US)
Pages (from-to)359-366
Number of pages8
JournalThe Lancet Oncology
Volume9
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

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Urinary Bladder Neoplasms
Case-Control Studies
Biomarkers
DNA
Cytosine
Odds Ratio
Folic Acid
Methylation
Leukocytes
Smoking
Vitamin B Complex
Densitometry
Genomic Instability
Capillary Electrophoresis
Spain
Digestion
Blood Cells
Urinary Bladder
Referral and Consultation
Alcohols

ASJC Scopus subject areas

  • Oncology

Cite this

Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study : a case-control study. / Moore, Lee E.; Pfeiffer, Ruth M.; Poscablo, Cristina; Real, Francisco X.; Kogevinas, Manolis; Silverman, Debra; García-Closas, Reina; Chanock, Stephen; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; Dosemeci, Mustafa; García-Closas, Montserrat; Esteller, Manel; Fraga, Mario; Rothman, Nathaniel; Malats, Núria.

In: The Lancet Oncology, Vol. 9, No. 4, 04.2008, p. 359-366.

Research output: Contribution to journalArticle

Moore, LE, Pfeiffer, RM, Poscablo, C, Real, FX, Kogevinas, M, Silverman, D, García-Closas, R, Chanock, S, Tardón, A, Serra, C, Carrato, A, Dosemeci, M, García-Closas, M, Esteller, M, Fraga, M, Rothman, N & Malats, N 2008, 'Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case-control study', The Lancet Oncology, vol. 9, no. 4, pp. 359-366. https://doi.org/10.1016/S1470-2045(08)70038-X
Moore, Lee E. ; Pfeiffer, Ruth M. ; Poscablo, Cristina ; Real, Francisco X. ; Kogevinas, Manolis ; Silverman, Debra ; García-Closas, Reina ; Chanock, Stephen ; Tardón, Adonina ; Serra, Consol ; Carrato, Alfredo ; Dosemeci, Mustafa ; García-Closas, Montserrat ; Esteller, Manel ; Fraga, Mario ; Rothman, Nathaniel ; Malats, Núria. / Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study : a case-control study. In: The Lancet Oncology. 2008 ; Vol. 9, No. 4. pp. 359-366.
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AU - Real, Francisco X.

AU - Kogevinas, Manolis

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AU - García-Closas, Reina

AU - Chanock, Stephen

AU - Tardón, Adonina

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AU - Dosemeci, Mustafa

AU - García-Closas, Montserrat

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