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Table 4 Studies of persistent organic pollutants (POPs) and other endocrine disruptors biomarkers and DNA methylation outcomes (6 studies available)

From: Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence

First author, year Design Population Size Men (%) a Age Range (yr) a Exposure assessment Exposure categories DNA methylation Assessment DNA methylation endpoint Chemical(s) (if PCBs, highest, lowest & median association and/or statistically significant) Association 95% Confidence Interval or p-value Adjustment Factors
Persistent Organic Pollutants
Rusiecki, 2008 [100] CS Greenland, Denmark (AMAP) 70 87 1967 Plasma by GC Per log-transformed ng/g lipid increase Peripheral leukocyte Average % methylation   Difference   QC reported. BEE or CH assessment NR. Models adjusted for age and smoking,
PCB 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, p,p’-DDT, p,p’-DDE, β-HCH, Hexachlorobenzene, Chlordane, Cis-chlordane, Oxychlordane, α-Chlordane, Mirex, Toxaphene, ΣPCBs, ΣPOPs Global by quantitative pyrosequencing in:
LINE-1 PCB 118 –0.73 P = 0.12
PCB 128 –0.01 P = 0.99
PCB 156, 170 –0.48 P = 0.26 and 0.15
Alu   PCB 156 –0.66 P < 0.01
PCB 52 –0.12 P = 0.36
PCB 99, 105 –0.51 P < 0.01 both
p,p’-DDT –0.26 P = 0.01
p,p’-DDE –0.38 P = 0.01
β-HCH –0.48 <0.01
Oxychlordane –0.32 <0.01
α-Chlordane –0.75 P = 0.05
Mirex –0.27 P = 0.01
ΣPCBs –0.56 <0.01
ΣPOPs –0.48 <0.01
Kim, 2010 [98] CS Uljin county, South Korea. 86 39.5 56.2 ± 7.0 Serum POPs by GC-HRMS Per ng/g lipid increase Whole blood. Average % methylation   Pearson correlation   QC reported. BEE or CH assessment NR. Models adjusted for age, sex, BMI, cigarette smoking, and alcohol drinking
PCB 74, 99, 105, 118, 138, 146, 153, 156, 157, 164, 167, 172, 177, 178, 180, 183 and 187, β-HCH, HCB, Heptachlor epoxide, Oxychlordane, trans-Nonachlor, p,p’-DDE, p,p’-DDD, p,p’-DDT, Mirex, BDE47, BDE99   Global by quantitative pyrosequencing in:  
LINE-1   PCB 157 –0.14 p ≥ 0.05
PCB 146 –0.02 p ≥ 0.05
PCB 105, 118, 156, 172, 180 –0.07 p ≥ 0.05
Alu   PCB 183 –0.23 p < 0.05
PCB 167 –0.05 p ≥ 0.05
PCB 177, 178 –0.14 p ≥ 0.05
Heptachlor epoxide, –0.23 <0.05
Oxychlordane, –0.28 <0.05
trans-nonachlordane, –0.28 <0.05
p,p’-DDE, –0.29 <0.01
p,p’-DDT, –0.22 <0.05
BDE47 –0.25 <0.05
Lind, 2013 [99] CS Uppsala, Sweden (PIVUS study) 519 52 70 Serumby HRGC-HRMS Per log-transformed ng/g lipid increase Leukocytes LUMA methylation indexb   Difference   QC NR. CH assessment NR. Same age. Models adjusted for sex and smoking status..
Global methylation by LUMA
PCB 74, 99, 105, 118, 126, 138, 153, 156, 157, 169, 170, 180, 189, 194, 206 and 209 Total PCB TEQ −1.67 −3.17, −0.16
Non-ortho PCB TEQ −1.76 −3.26, −0.26
Octachlorodibenzo-p-dioxin, HCB, TNC, p,p′-DDE, BDE47 Mono-ortho PCB TEQ 0.11 −1.37, 1.60
PCB 169 −3.27 −6.92, 0.37
PCB 206 −0.16 −3.71, 3.38
PCB 189 −0.56 −3.10, 1.97
Octachlorodibenzo-p-dioxin, −3.19 −5.98, −0.39
p,p′-DDE −2.87 −4.74, −1.00
Itoh, 2014 [20] CS Japan 399 0 53.9 ±10.2 Serum by GC-HRMS Per increase in 1 quartile categories (as an ordinal variable) Peripheral leukocytes 1 – (LUMA methylation indexb)     QC NR. CH assessment NR. Models adjusted for age, BMI, smoking status and alcohol drinking. Lipid-corrected values.
PCB 17, 28, 52/69, 48/47, 74, 66, 90/101, 99, 118, 114, 105, 146, 153, 164/163, 138, 128/162, 167, 156, 182/187, 183, 177, 180, 170, 189, 202, 198/199, 196, 203, 194, 208, 206 and 209, p,p’-DDE, o,p’-DDT, p,p’-DDT, trans-Nonachlor, cis-Nonachlor, Oxychlordane, β-HCH, HCB, Mirex Global methylation by LUMA PCB196 −0.009 −0.38, 0.36
PCB74 −0.64 −1.08, −0.20
PCB28 and 66 −0.23 −0.59, 0.12
PCB17 −0.43 −0.78, −0.08
PCB52/69 −0.33 −0.67, −0.0007
PCB114 −0.46 −0.88, −0.05
PCB183 −0.45 −0.82, −0.07
p,p’-DDE, −0.77 −1.12, −0.42
o,p’-DDT, −0.75 −1.11, −0.40
p,p’-DDT , −0.83 −1.17, −0.49
trans-Nonachlor, −0.44 −0.84, −0.04
Oxychlordane, −0.53 −0.90, −0.15
β-HCH, −0.73 −0.79, −0.35
HCB, −0.41 −0.79, −0.03
ΣPCBs −0.19 −0.59, 0.20
Perfluorinated compounds
Watkins, 2014 [101] CS Mid-Ohio River Valley, US (C8 Health Project) 671 47 41.8 (20 to 80) Blood by HPLC separation and detection by ITMS. Per IQR increase in mean log ng/mL levels at 2 repeated visits 5 years apart Peripheral leukocyte    Difference   QC and CH assessment NR. Models adjusted for age, gender, BMI, smoking and current drinker status
Global by quantitative pyrosequencing in LINE-1 Average % methylation
PFOA 106 ng/mL −0.041 −0.098, 0.016
PFOS 12 ng/mL 0.204 0.090, 0.318
PFNA 0.8 ng/mL 0.064 −0.030, 0.158
PFHxS 2.6 ng/mL 0.020 −0.051, 0.091
Bisphenol A
Hanna, 2012 [29] CS U.S. (Study of Metals and Assisted Reproductive Technologies [SMART]) 35 0 Mean 36 (28 to 44) Serum Above and below the median Whole blood DNA      Normalization. QC reported. BEE NR. CH partially addressed. Data unadjusted. MCC NR.
Unconjugated BPA by HPLC
Median =2.39 μg/L Site specific Illumina GoldenGate and bisulfite pyrosequencing of significant regionsb 1,505 CpG sites % methylation A trend towards hypomethylation if difference score > |30| (p < 0.05)  
TSP50
26% decrease in mean DNA m P = 0.005
r pearson = -0.51 P = 0.001
Global by bisulfite pyrosequencing of LINE-1 ~0.2% increase in median DNAm P = 0.56
  1. CH: cell heterogeneity; BDE, polybrominated diphenyl ether; BEE: batch effect evaluation; BMI: body mass index; CDT, Comparative Toxicogenomics Database; CC: case-control; CI: confidence interval; CO: cohort; CS: cross-sectional; DNAm: DNA methylation; DDT, dichlorodiphenyl trichloroethane; DDE, dichlorodiphenyldichloroethylene; GC: gas chromatography; HPLC: high-performance liquid chromatography; HRGC-HRMS: high-resolution chromatography coupled to high-resolution mass spectometry; HRMS: high resolution mass spectrometry; IQR: interquartile range; ITMS: isotope-dilution tandem mass spectrometry; LOD: limit of detection; LUMA: Luminometric Methylation Assay; MCC: multiple comparisons correction; NR: not reported; PBDEs, polybrominated diphenyl ether; QC: quality control.
  2. aSociodemographic data available in the article, not necessarily in the subsample without missing values in DNA methylation or exposures.
  3. bSignificance was defined as a difference score > |13| (p < 0.05) and >10% absolute difference between the means for each group. b LUMA methylation index ranges from 1 (fully demethylated DNA) to 0 (fully methylated DNA).