Implications of LINE1 Methylation for Bladder Cancer Risk in Women.
By: Wilhelm CS, Kelsey KT, Butler R, Plaza S, Gagne L, Zens MS, Andrew AS, Morris S, Nelson HH, Schned AR, Karagas MR, Marsit CJ.

Authors' Affiliations: Departments of Community Health Center for Environmental Health and Technology and Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island; Departments of Community and Family Medicine, and Pathology, Dartmouth Medical School, Lebanon, New Hampshire; Research Reactor Center, University of Missouri, Columbia, Missouri, and Masonic Cancer Center, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota.
Clin Cancer Res. 2010 Mar 1; 16(5):1682−9. Epub 2010 Feb 23.

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. Clin Cancer Res; 16(5); 1682−9.

PMID: 20179218 [PubMed − in process] Source: National Library of Medicine.






* Albert Einstein College of Medicine has been
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