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Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case-control study

Citation

Dugue, PA and Brinkman, MT and Milne, RL and Wong, EM and Fitzgerald, LM and Bassett, JK and Joo, JE and Jung, CH and Makalic, E and Schmidt, DF and Park, DJ and Chung, J and Ta, AD and Bolton, DM and Lonie, A and Longano, A and Hopper, JL and Severi, G and Saffery, R and English, DR and Southey, MC and Giles, GG, Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case-control study, British Journal of Cancer, 115, (6) pp. 664-673. ISSN 0007-0920 (2016) [Refereed Article]


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Copyright Statement

Copyright 2016 Cancer Research UK.

DOI: doi:10.1038/bjc.2016.237

Abstract

BACKGROUND: Global DNA methylation has been reported to be associated with urothelial cell carcinoma (UCC) by studies using blood samples collected at diagnosis. Using the Illumina HumanMethylation450 assay, we derived genome-wide measures of blood DNA methylation and assessed them for their prospective association with UCC risk.

METHODS: We used 439 case-control pairs from the Melbourne Collaborative Cohort Study matched on age, sex, country of birth, DNA sample type, and collection period. Conditional logistic regression was used to compute odds ratios (OR) of UCC risk per s.d. of each genome-wide measure of DNA methylation and 95% confidence intervals (CIs), adjusted for potential confounders. We also investigated associations by disease subtype, sex, smoking, and time since blood collection.

RESULTS: The risk of superficial UCC was decreased for individuals with higher levels of our genome-wide DNA methylation measure (OR=0.71, 95% CI: 0.54-0.94; P=0.02). This association was particularly strong for current smokers at sample collection (OR=0.47, 95% CI: 0.27-0.83). Intermediate levels of our genome-wide measure were associated with decreased risk of invasive UCC. Some variation was observed between UCC subtypes and the location and regulatory function of the CpGs included in the genome-wide measures of methylation.

CONCLUSIONS: Higher levels of our genome-wide DNA methylation measure were associated with decreased risk of superficial UCC and intermediate levels were associated with reduced risk of invasive disease. These findings require replication by other prospective studies.

Item Details

Item Type:Refereed Article
Keywords:urothelial cell carcinoma, bladder cancer, DNA methylation, peripheral blood, biomarker, EWAS
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. Genome Methylation and Epigenomics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:110855
Year Published:2016
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-18
Last Modified:2017-11-02
Downloads:2 View Download Statistics

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