Table 2.

Relative risk of baseline folate intake and colon cancer according to LINE-1 methylation level among 88,691 women from the Nurses’ Health Study (NHS) and 47,363 men from the Health Professionals Follow-up Study (HPFS).

	Energy-adjusted Folate Intake, µg/day				Ptrend
	<200	200–299	300–399	≥400
All cancer cases
No. cases / Person-years	101 / 461357	166 / 756398	132 / 472313	210 / 873018
Age-adjusted RR (95% CI)	1.0	0.84 (0.66–1.08)	0.91 (0.70–1.19)	0.79 (0.62–1.00)	0.07
Multivariate RR (95% CI)*	1.0	0.80 (0.62–1.03)	0.82 (0.62–1.09)	0.76 (0.59–0.99)	0.16
LINE-1 low (<55%) cancer cases†
No. cases / Person-years	31 / 461416	34 / 756511	36 / 472406	47 / 873179
Age-adjusted RR (95% CI)	1.0	0.57 (0.35–0.92)	0.83 (0.51–1.34)	0.58 (0.37–0.92)	0.05
Multivariate RR (95% CI)*	1.0	0.54 (0.33–0.88)	0.75 (0.46–1.23)	0.57 (0.36–0.91)	0.08
LINE-1 medium (55–64%) cancer cases†
No. cases / Person-years	47 / 461399	77 / 756478	46 / 472394	95 / 873124
Age-adjusted RR (95% CI)	1.0	0.84 (0.58–1.21)	0.68 (0.45–1.02)	0.76 (0.53–1.08)	0.21
Multivariate RR (95% CI)*	1.0	0.80 (0.55–1.15)	0.61 (0.40–0.93)	0.74 (0.51–1.06)	0.31
LINE-1 high (≥65%) cancer cases†
No. cases / Person-years	23 / 461420	55 / 756494	50 / 472383	68 / 873145
Age-adjusted RR (95% CI)	1.0	1.23 (0.75–2.00)	1.51 (0.92–2.48)	1.11 (0.69–1.79)	0.92
Multivariate RR (95% CI)*	1.0	1.17 (0.72–1.90)	1.36 (0.82–2.26)	1.08 (0.66–1.75)	0.94

^*Multivariate models are adjusted for age (continuous), gender, energy intake (kcal), screening sigmoidoscopy or colonoscopy (yes/no), family history of colorectal cancer (yes/no), aspirin use (≥2 tablets/week or less), smoking (packyears), physical activity in METs (quintiles), body mass index in five categories (<21, 21–22.9, 23–24.9, 25–29.9, 30+), colon polyps (yes/no), beef intake (quintiles), calcium intake (quintiles), multi-vitamin use (yes/no), alcohol use (none, <5, 5–14.9, ≥15g/day), and intake of vitamin B₆, B₁₂, and methionine (quintiles).

^†LINE-1, long interspersed nucleotide element-1.