Implications of LINE1 Methylation for Bladder Cancer Risk in Women

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2010 Feb 25

PMID 20179218

Citations 97

Authors

Charlotte S Wilhelm

Karl T Kelsey

Rondi Butler

Silvia Plaza

Luc Gagne

M Scot Zens

Angeline S Andrew

Steven Morris

Heather H Nelson

Alan R Schned

Margaret R Karagas

Carmen J Marsit

Affiliations

Soon will be listed here.

Abstract

Purpose: Epigenetic alterations including changes to cellular DNA methylation levels contribute to carcinogenesis and may serve as powerful biomarkers of the disease. This investigation sought to determine whether hypomethylation at the long interspersed nuclear elements (LINE1), reflective of the level of global DNA methylation, in peripheral blood-derived DNA is associated with increased risk of bladder cancer.

Experimental Design: LINE1 methylation was measured from blood-derived DNA obtained from participants of a population-based incident case-control study of bladder cancer in New Hampshire. Bisulfite-modified DNA was pyrosequenced to determine LINE1 methylation status; a total of 285 cases and 465 controls were evaluated for methylation.

Results: Being in the lowest LINE1 methylation decile was associated with a 1.8-fold increased risk of bladder cancer [95% confidence interval (95% CI), 1.12-2.90] in models controlling for gender, age, and smoking, and the association was stronger in women than in men (odds ratio, 2.48; 95% CI, 1.19-5.17 in women; and odds ratio, 1.47; 95% CI, 0.79-2.74 in men). Among controls, women were more likely to have lower LINE1 methylation than men (P = 0.04), and levels of arsenic in the 90th percentile were associated with reduced LINE1 methylation (P = 0.04).

Conclusions: LINE1 hypomethylation may be an important biomarker of bladder cancer risk, especially among women.

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