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Clin Cancer Res. 2016 Apr 15;22(8):2074-82. doi: 10.1158/1078-0432.CCR-15-0977. Epub 2015 Dec 11.

Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case-Control Study.

Author information

1
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México.
2
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México.
4
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. xwu@mdanderson.org.

Abstract

PURPOSE:

Genomic DNA hypomethylation is a hallmark of most cancer genomes, promoting genomic instability and cell transformation. In the present study, we sought to determine whether global DNA methylation in peripheral blood is associated with risk of renal cell carcinoma (RCC).

EXPERIMENTAL DESIGN:

A retrospective case-control study consisting of 889 RCC cases and an equal number of age, gender, and ethnicity-matched controls was applied. Global DNA methylation was measured as 5-mC% content. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between DNA methylation level and the risk of RCC.

RESULTS:

The median 5-mC% was significantly lower in cases than in healthy controls (P< 0.001). In multivariate logistic regression analysis, individuals in the lowest tertile (T1) of 5-mC% had higher risk of RCC with OR of 1.40 (95% CI, 1.06-1.84), compared with individuals in the highest tertile (T3;Pfor trend= 0.02). When stratified by RCC risk factors, associations between hypomethylation and increased RCC risk appeared to be stronger among males (OR, 1.61;Pfor trend= 0.01), younger age (OR, 1.47;Pfor trend= 0.03), never smokers (OR, 1.55;Pfor trend= 0.02), family history of other cancer (OR, 1.64;Pfor trend= 1.22E-03), and late stage (OR, 2.06,Pfor trend= 4.98E-04). Additionally, we observed significant interaction between gender and 5-mC% in elevating RCC risk (Pfor interaction= 0.03).

CONCLUSIONS:

Our findings suggest an association between global DNA hypomethylation and RCC risk. To establish global DNA hypomethylation as a risk factor for RCC, future prospective studies are warranted. This study may provide further understanding of the etiology of RCC tumorigenesis.

PMID:
26655847
PMCID:
PMC4834236
DOI:
10.1158/1078-0432.CCR-15-0977
[Indexed for MEDLINE]
Free PMC Article

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