Implications of LINE1 Methylation for Bladder Cancer Risk in Women

• Published in: Clinical cancer research Vol. 16; no. 5; pp. 1682 - 1689
• Main Authors: WILHELM, Charlotte S, KELSEY, Karl T, KARAGAS, Margaret R, MARSIT, Carmen J, BUTLER, Rondi, PLAZA, Silvia, GAGNE, Luc, ZENS, M. Scot, ANDREW, Angeline S, MORRIS, Steven, NELSON, Heather H, SCHNED, Alan R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.2010
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - genetics; DNA Methylation; Female; Genetic Predisposition to Disease - genetics; Humans; Long Interspersed Nucleotide Elements - genetics; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Risk Factors; Tumors of the urinary system; Urinary Bladder Neoplasms - genetics; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Human; Urinary system disease; Risk factor; Adult; Female; Bladder disease; Urinary tract disease; Malignant tumor; Woman; Methylation; Bladder cancer; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-09-2983

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