title: Prospective changes in global DNA methylation and cancer incidence and mortality.
abstract: Methylation of repetitive elements Alu and LINE-1 in humans is considered a surrogate for global DNA methylation. Previous studies of blood-measured Alu/LINE-1 and cancer risk are inconsistent.
  
  
  
  We studied 1259 prospective methylation measurements from blood drawn 1-4 times from 583 participants from 1999 to 2012. We used Cox regression to evaluate time-dependent methylation as a biomarker for cancer risk and mortality, and linear regression to compare mean differences in methylation over time by cancer status and analyse associations between rate of methylation change and cancer.
  
  
  
  Time-dependent LINE-1 methylation was associated with prostate cancer incidence (HR: 1.38, 95% CI: 1.01-1.88) and all-cancer mortality (HR: 1.41, 95% CI: 1.03-1.92). The first measurement of Alu methylation (HR: 1.39, 95% CI: 1.08-1.79) was associated with all-cancer mortality. Participants who ultimately developed cancer had lower mean LINE-1 methylation than cancer-free participants 10+ years pre-diagnosis (P<0.01). Rate of Alu methylation change was associated with all-cancer incidence (HR: 3.62, 95% CI: 1.09-12.10).
  
  
  
  Our results add longitudinal data on blood Alu and LINE-1 methylation and cancer, and potentially contribute to their use as early-detection biomarkers. Future larger studies are needed and should account for the interval between blood sample collection and cancer diagnosis.
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.|Division of Epidemiology/Biostatistics, School of Public Health, University of Illinois-Chicago, 1603 W. Taylor Street, Chicago, IL 60612, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Joyce
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.|Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Vanderbilt University Medical Center, 2525 West End Avenue, Suite 319, Nashville, TN 37203, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Vanderbilt University Medical Center, 2525 West End Avenue, Suite 319, Nashville, TN 37203, USA.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hibler
authors.affiliation: Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, 676 N. St Clair Street, 8th Floor, Chicago, IL 60611, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Division of Population Science, Sidney Kimmel Cancer Center, Thomas Jefferson University, 834 Chestnut Street, Suite 314, Philadelphia, PA 19107, USA.
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.affiliation: VA Normative Aging Study, VA Boston Healthcare System, 150 South Huntington Avenue, Boston, MA 02130, USA.|Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Molecular Epidemiology and Environmental Epigenetics Laboratory, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, San Barnaba 8, Milan 20122, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.|Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Olson Pavilion 8350, Chicago, IL 60611, USA.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements / Q000235:genetics; D015415:Biomarkers; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans; D015994:Incidence; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers