DNA methylation in white blood cells

Figures & data

Figure 1 Epidemiologic studies investigating the association between WBC global DNA methylation and cancer risk (comparing lowest quantile to highest quantile). Tertiles used are from references 14–16 and 19–21. Quartiles used are from reference 18. Deciles used are from reference 17. +, upper 95% confidence limit exceeds 10.

Figure 2 Epidemiologic studies investigating the association between WBC gene-specific DNA methylation and cancer risk. Methylation cutpoints specific to each study, for details see references 22–27.

Table 1 Risk factors investigated in studies of WBC DNA global methylation by assay type

	Some support for lower global methylation	Little to no support of an association with global methylation	Some support for higher global methylation
Demographics
Age	%5-mC 33 [^3H]-methyl35 LINE-1 36 Alu34,36,37,41	%5-mC18 LINE-1 17,21,37–41
Gender (Females versus Males)	%5-mC33 LINE-1 17,21,37–39,46 Alu46	%5-mC18 LINE-1 41 Alu41	LUMA 46 Alu37
Race (Black versus White)	[^3H]-methyl 53 LINE-1 39	CCGG 54	LINE-1 21
Environmental factors
Benzene	LINE-1 55 Alu55
Persistent Organic Pollutants	LINE-1 57 Alu41,57	LINE-1 41
Lead	LINE-1 58,59 Alu58	Alu59
Arsenic			[^3H]-methyl 35
Air Pollution	LINE-1 62–64 Alu62,64	Alu63
Behavioral Risk Factors
Adult Active Cigarette Smoking		%5-mC18,20 CCGG68 LINE-1 17,21,37,41,57,69 Alu37,41,57
Prenatal Cigarette Smoking	LINE-1 73 Sat273	Alu73	[^3H]-methyl53
Alcohol Drinking	Alu37	LINE-1 21,37,41,79 Alu41	CCGG77,78
Higher Body size	LINE-1 80	LINE-1 37,41,79 Alu 37,41
Higher Physical Activity			LINE-1 79
Low Dietary Folate		%5-mc18,81 LINE-1 21,79 Alu79

Table 2 Risk factors investigated in studies of gene-specific DNA methylation

	Some support for gene-specific methylation	Little to no support of an association with gene-specific methylation
Demographics
Age	PKDIP2 34 GUK1 34 CALCA 42 MGMT 42	H19 82 IGF2 82
Gender (Females versus Males)	MAOA 52 CALCA 42 MTHFR 42 MGMT 42 DRD4 52 SERT 52 F8 46	H19 82 IGF2 82
Environmental factors
Benzene	p16 56 p15 55 MAGE-1 55	p15 56
Air pollution	NOS2 62
Arsenic	p1660,61 p5360
Behavioral Risk Factors
Cigarette Smoking	F2RL3 10
Prenatal Cigarette Smoking	IGF2 75 BDNF 74
Alcohol Drinking	HERP 78

Table 3 Folate intervention studies

Author	Subjects	Study	Folate Intake	Duration	Analysis Method	Change from Baseline
Jacob et al.84	8 F (49–63 years)	Controlled feeding study	56–510 µg/d	91 days	[^3H]-methyl	Significant decrease during depletion Significant increase during supplementation
Fenech et al.85	34 M 30 F (18–35 years)	Double-blind, randomized, placebo-controlled	700 µg/d	12 weeks	[^3H]-methyl	No significant change
			2,000 µg/d	12 weeks		No significant change
Rampersaud et al.86	33 F (60–85 years)	Controlled feeding study	118 µg/d	7 weeks	[^3H]-methyl	Significant decrease during depletion
			200 or 415 µg/d	7 weeks		12 weeks
Shelnutt et al.87	41 F (20–30 years)	Controlled feeding study	115 µg/d	7 weeks	[^3H]-methyl	No significant change
					5-mC	No significant change
			400 µg/d	7 weeks	[^3H]-methyl	No significant change
					5-mC	Significant increase during supplementation only in MTHFR 677TT genotype
Basten et al.88	30 M 31 F (20–60 years)	Double-blind, randomized, placebo-controlled	1,200 µg/d	12 weeks	[^3H]-methyl	No significant change
Axume et al.54	28 F (18–45 years)	Controlled feeding study	135 µg/d	7 weeks	CCGG methylation	No significant change
			400 or 800 µg/d	7 weeks		No significant change
Axume89	43 F (18–45 years)	Controlled feeding study	135 µg/d	7 weeks	CCGG methylation	No significant change
			400 or 800 µg/d	7 weeks		Significant decrease during supplementation only in MTHFR 677TT genotype

*p < 0.05.

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