Implications of LINE1 methylation for bladder cancer risk in women.
OBJECTIVE
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.


METHODS
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.
Wilhelm
Charlotte S
CS
Department of Community Health Center for Environmental Health, Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
Kelsey
Karl T
KT
Butler
Rondi
R
Plaza
Silvia
S
Gagne
Luc
L
Zens
M Scot
MS
Andrew
Angeline S
AS
Morris
Steven
S
Nelson
Heather H
HH
Schned
Alan R
AR
Karagas
Margaret R
MR
Marsit
Carmen J
CJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D014408:Biomarkers, Tumor