TY - JOUR
T1 - Prospective changes in global DNA methylation and cancer incidence and mortality
AU - Joyce, Brian T.
AU - Gao, Tao
AU - Zheng, Yinan
AU - Liu, Lei
AU - Zhang, Wei
AU - Dai, Qi
AU - Shrubsole, Martha J.
AU - Hibler, Elizabeth A.
AU - Cristofanilli, Massimo
AU - Zhang, Hu
AU - Yang, Hushan
AU - Vokonas, Pantel
AU - Cantone, Laura
AU - Schwartz, Joel
AU - Baccarelli, Andrea
AU - Hou, Lifang
N1 - Funding Information:
This work was supported by the Ziff Fund at the Harvard University Center for the Environment, NIEHS grants RO1-ES015172, 2RO1-ES015172, and ES014663.
Publisher Copyright:
© 2016 Cancer Research UK.
PY - 2016/8/9
Y1 - 2016/8/9
N2 - Background: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.Methods: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.Results: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).Conclusions: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.
AB - Background: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.Methods: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.Results: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).Conclusions: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.
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U2 - 10.1038/bjc.2016.205
DO - 10.1038/bjc.2016.205
M3 - Article
C2 - 27351216
AN - SCOPUS:84976350871
SN - 0007-0920
VL - 115
SP - 465
EP - 472
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -