LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants.

Abstract

Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2-Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2-Q4 vs. Q1 OR = 1.48, 95% CI: 1.00-2.20) and statistically significant among male smokers (Q2-Q4 vs. Q1 OR = 1.83, 95% CI: 1.14-2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2-Q4 vs. Q1: OR = 2.31, 95% CI: 1.62-3.30) and a highly significant trend was observed (P = 8.7 × 10(-7)). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52-2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers.

• Authors: Gabriella Andreotti, Sara Karami, Ruth M Pfeiffer, Lauren Hurwitz, Linda M Liao, Stephanie J Weinstein, Demetrius Albanes, Jarmo Virtamo, Debra T Silverman, Nathaniel Rothman, Lee E Moore
• Journal: Epigenetics (Epigenetics) Vol. 9 Issue 3 Pg. 404-15 (Mar 2014) ISSN: 1559-2308 [Electronic] United States
• PMID: 24316677 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• DNA

Topics

• Aged
• Cohort Studies
• DNA (blood)
• DNA Methylation
• Europe
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Long Interspersed Nucleotide Elements
• Male
• Middle Aged
• Prognosis
• Risk Factors
• Smoking (adverse effects)
• United States
• Urinary Bladder Neoplasms (blood, diagnosis, genetics)