Table 3

Risk of colon cancer according to baseline quintiles of one-carbon nutrient intake by tumoral LINE-1 methylation level among 88 691 women and 47 363 men (NHS and HPFS combined)

Energy-adjusted daily one-carbon nutrient intake
RR (95% CI)*Ptrend
Methionine (g)Q1Q2Q3Q4Q5
All cancer cases
Cases/person-years136/511 094140/512 59299/517 670125/512 400109/509 330
Age-adjusted1.01.02 (0.81–1.30)0.71 (0.55–0.92)0.88 (0.69–1.12)0.72 (0.56–0.93)0.22
Multivariate*1.01.03 (0.81–1.30)0.72 (0.55–0.93)0.91 (0.71–1.17)0.77 (0.59–1.00)0.10
LINE-1 low (<55%)
Cases/person-years33/511 19937/512 68529/517 73423/512 49126/509 403
Age-adjusted1.01.12 (0.70–1.78)0.86 (0.52–1.41)0.67 (0.39–1.14)0.71 (0.42–1.18)0.51
Multivariate*1.01.12 (0.70–1.79)0.86 (0.52–1.43)0.69 (0.40–1.18)0.76 (0.45–1.27)0.36
LINE-1 medium (55–64%)
Cases/person-years54/511 17471/512 65336/517 72760/512 45744/509 383
Age-adjusted1.01.31 (0.92–1.86)0.65 (0.42–0.99)1.06 (0.74–1.53)0.73 (0.49–1.09)0.06
Multivariate*1.01.31 (0.92–1.87)0.66 (0.43–1.00)1.10 (0.76–1.60)0.78 (0.52–1.17)0.03
LINE-1 high (≥65%)
Cases/person-years49/511 17132/514 77234/512 68642/517 72739/509 393
Age-adjusted1.00.65 (0.42–1.02)0.67 (0.44–1.04)0.82 (0.54–1.24)0.71 (0.47–1.09)0.57
Multivariate1.00.65 (0.42–1.02)0.68 (0.44–1.06)0.85 (0.56–1.29)0.76 (0.50–1.17)0.81
Vitamin B6 (mg)Q1Q2Q3Q4Q5PTrend
All cancer cases
Cases/person-years135/518 267134/514 617116/513 71198/510 531126/505 964
Age-adjusted1.00.91 (0.71–1.15)0.70 (0.55–0.90)0.60 (0.47–0.78)0.77 (0.60–0.98)0.47
Multivariate*1.00.92 (0.73–1.18)0.75 (0.58–0.97)0.66 (0.51–0.87)0.88 (0.68–1.11)0.40
LINE-1 low (<55%)
Cases/person-years36/518 36031/514 69527/513 79322/510 60632/506 058
Age-adjusted1.00.79 (0.49–1.27)0.61 (0.37–1.01)0.51 (0.30–0.86)0.73 (0.45–1.18)0.88
Multivariate*1.00.80 (0.50–1.30)0.65 (0.40–1.08)0.56 (0.33–0.95)0.84 (0.52–1.36)0.83
LINE-1 medium (55–64%)
Cases/person-years62/518 33359/514 67748/513 77149/510 57347/506 040
Age-adjusted1.00.87 (0.61–1.24)0.63 (0.43–0.92)0.66 (0.45–0.96)0.62 (0.43–0.91)0.91
Multivariate*1.00.89 (0.62–1.27)0.68 (0.46–0.99)0.72 (0.49–1.06)0.71 (0.48–1.05)0.86
LINE-1 high (≥65%)
Cases/person-years37/51835344/51468141/51377527/51059647/506037
Age-adjusted1.01.09 (0.70–1.68)0.91 (0.51–1.42)0.61 (0.37–1.00)1.05 (0.68–1.61)0.29
Multivariate1.01.11 (0.72–1.72)0.97 (0.62–1.52)0.67 (0.41–1.10)1.20 (0.77–1.86)0.25
Vitamin B12 (g)Q1Q2Q3Q4Q5PTrend
All cancer cases
Cases/person-years132/515939120/515415120/514236123/509953114/507543
Age-adjusted1.00.88 (0.69–1.13)0.85 (0.66–1.09)0.83 (0.65–1.06)0.74 (0.58–0.96)0.82
Multivariate*1.00.87 (0.68–1.11)0.84 (0.66–1.08)0.86 (0.67–1.11)0.77 (0.59–0.99)0.86
LINE-1 low (<55%)
Cases/person-years34/516 03737/515 48726/514 31827/510 04024/507 630
Age-adjusted1.01.05 (0.66–1.68)0.71 (0.43–1.19)0.71 (0.43–1.17)0.61 (0.36–1.02)0.88
Multivariate*1.01.04 (0.65–1.65)0.71 (0.43–1.18)0.73 (0.44–1.22)0.62 (0.37–1.06)0.84
LINE-1 medium (55–64%)
Cases/person-years54/516 01149/515 47451/514 30157/510 01254/507 596
Age-adjusted1.00.88 (0.60–1.30)0.88 (0.60–1.29)0.94 (0.65–1.37)0.86 (0.59–1.25)0.62
Multivariate*1.00.87 (0.59–1.28)0.88 (0.60–1.29)0.97 (0.67–1.42)0.89 (0.61–1.30)0.61
LINE-1 high (≥65%)
Cases/person-years44/516 01634/515 48443/514 30039/510 02736/507 614
Age-adjusted1.00.75 (0.48–1.17)0.91 (0.60–1.39)0.79 (0.52–1.22)0.71 (0.45–1.10)0.99
Multivariate1.00.74 (0.47–1.16)0.91 (0.60–1.39)0.82 (0.53–1.27)0.73 (0.47–1.13)0.97
Alcohol (g)No alcohol<5g/day5–14.9g/day≥15g/dayPTrend
All cancer cases
Cases/person-years157/759 573165/800 196145/608 441142/395 877
Age-adjusted1.01.06 (0.85–1.31)1.12 (0.89–1.40)1.51 (1.21–1.90)0.0001
Multivariate*1.01.08 (0.88–1.39)1.10 (0.88–1.39)1.41 (1.11–1.79)0.01
LINE-1 low (<55%)
Cases/person-years35/758 68737/800 30539/608 54137/395 979
Age-adjusted1.01.06 (0.67–1.69)1.35 (0.86–2.13)1.79 (1.12–2.84)0.004
Multivariate*1.01.07 (0.68–1.71)1.34 (0.85–2.12)1.67 (1.04–2.67)0.02
LINE-1 medium (55–64%)
Cases/person-years69/758 65070/800 27357/608 52669/395 945
Age-adjusted1.01.02 (0.73–1.42)1.00 (0.70–1.41)1.67 (1.19–2.33)0.002
Multivariate*1.01.03 (0.74–1.44)0.99 (0.69–1.41)1.55 (1.10–2.18)0.03
LINE-1 high (≥65%)
Cases/person-years53/758 65858/800 28549/608 52836/395 970
Age-adjusted1.01.10 (0.76–1.59)1.11 (0.76–1.64)1.13 (0.74–1.73)0.48
Multivariate1.01.12 (0.77–1.62)1.10 (0.75–1.63)1.06 (0.69–1.62)0.87

  • ↵* All models are adjusted for age (continuous), energy intake, gender, screening sigmoidoscopy or colonoscopy, family history of colorectal cancer, aspirin use, smoking, physical activity in metabolic equivalents (METs), baseline body mass index, a history of colon polyps, beef intake, calcium, multi-vitamin use, and baseline folate, vitamin B6, B12, methionine and alcohol if not primary exposure.

  • HPFS, Health Professionals Follow-up Study; LINE-1, long interspersed nucleotide element-1; NHS, Nurses' Health Study.