title: Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case-Control Study.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Julia
authors.initials: J
authors.lastname: Mendoza-Pérez
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Herrera
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Surena F
authors.initials: SF
authors.lastname: Matin
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David W
authors.initials: DW
authors.lastname: Chang
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. xwu@mdanderson.org.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015897:Comorbidity; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors