Article Figures & Data
Tables
- Table 1.
Comparison of individuals in the Aspirin/Folate Polyp Prevention Trial who participated and did not participate in this study
Characteristics Individuals excluded in this study Individuals included in this study P* No. participants 733 388 Age at baseline, mean ± SD (y) 57.3 ± 9.9 57.8 ± 9.1 0.83† Male, n (%) 466 (63.6) 246 (63.4) 0.96* Body mass index >30 kg/m2, n (%) 176 (24.0) 77 (19.9) 0.12* Current cigarette smoker, n (%) 106 (14.5) 58 (15.0) 0.97* Colorectal cancer in first-degree relative, n (%) 224 (36.9) 117 (37.9) 0.78* Self-identified as White, n (%) 633 (86.4) 325 (83.8) 0.24* Aspirin Treatment Group‡, n (%) 489 (66.7) 260 (67.0) 0.92* Folate Treatment Group, n (%) 318 (50.2) 198 (51.0) 0.81* Baseline RBC folate, mean ± SD (ng/mL) 414.9 ± 6.3 396.4 ± 7.2 0.04§ Baseline plasma folate, mean ± SD (nmol/L) 24.8 ± 0.75 20.9 ± 0.80 <0.01§ Baseline plasma B2, mean ± SD (nmol/L) 30.9 ± 2.1 25.7 ± 2.3 0.38§ Baseline plasma B6, mean ± SD (nmol/L) 80.7 ± 3.5 76.5 ± 4.6 0.44§ Baseline plasma B12, mean ± SD (pmol/L) 319.3 ± 6.2 338.6 ± 9.1 0.09§ Baseline plasma homocysteine, mean ± SD (μmol/L) 10.1 ± 4.2 9.9 ± 2.95 0.80§ Multivitamin use, n (%) 265 (36.3) 130 (33.5) 0.36§ Dietary intake Folate intake, mean ± SD (μg/d) 327.9 ± 6.1 305.0 ± 7.7 0.01† Vitamin B2, mean ± SD (mg/d) 1.79 ± 0.03 1.72 ± 0.43 0.11† Vitamin B6, mean ± SD (mg/d) 1.67 ± 0.03 1.64 ± 0.04 0.26† Vitamin B12, mean ± SD (mg/d) Alcohol (drinks/d), n (%) 217 (31.5) 123 (33.0) 0.21* None 341 (49.4) 165 (44.2) ≤1 132 (19.1) 85 (22.8) ≥2 Adenoma characteristics (at baseline)∥ No. lifetime adenomas (mean ± SD) 2.44 ± 2.30 2.22 ± 1.94 0.11§ Large baseline adenomas (>1 cm), n (%) 157 (21.4) 96 (24.7) 0.21* Baseline adenomas with villous histology, n (%) 107 (14.6) 49 (12.6) 0.37* Baseline adenomas with proximal location, n (%) 342 (46.7) 164 (42.3) 0.16* - Table 2.
Association between LINE-1 methylation and selected demographic and lifestyle variables
Counts* Overall Left side Right side P† NT/NL/NR Mean (95% CI) P‡ Mean (95% CI) P‡ Mean (95% CI) P‡ Age (y) Q1 (30-52) 107/107/106 64.75 (64.24-65.26) 0.49 65.41 (64.81-66.00) 0.63 64.09 (63.51-64.68) 0.46 0.27 Q2 (53-58) 96/96/96 63.94 (63.40-64.48) 64.17 (63.55-64.78) 63.71 (63.05-64.38) Q3 (59-64) 93/92/92 64.39 (63.87-64.92) 64.93 (64.24-65.62) 63.87 (63.28-64.45) Q4 (65-78) 92/92/91 64.32 (63.80-64.85) 64.92 (64.21-65.62) 63.72 (63.17-64.27) Sex Male 246/245/244 64.33 (64.02-64.64) 0.72 64.86 (64.45-65.26) 0.85 63.80 (63.44-64.17) 0.66 0.81 Female 142/141/142 64.44 (63.95-64.93) 64.92 (64.36-65.48) 63.95 (63.43-64.46) Body mass index (kg/m2) Normal 113/113/112 64.37 (63.87-64.86) 0.93 64.85 (64.28-65.43) 0.70 63.89 (63.31-64.47) 0.79 0.77 Overweight 195/195/193 64.37 (64.01-64.73) 64.84 (64.39-65.29) 63.90 (63.49-64.30) Obese 79/78/79 64.40 (63.78-65.02) 65.05 (64.24-65.86) 63.77 (63.10-64.44) Smoking Never 164/164/163 64.39 (64.02-64.76) 0.44 65.12 (64.66-65.57) 0.62 63.65 (63.23-64.08) 0.08 0.04 Former 163/163/163 64.24 (63.82-64.67) 64.65 (64.10-65.21) 63.84 (63.38-64.30) Current 60/59/58 64.73 (63.96-65.49) 64.88 (64.05-65.71) 64.57 (63.65-65.50) Alcohol Never 123/123/122 64.54 (64.13-64.95) 0.74 65.37 (64.78-65.95) 0.14 63.70 (63.27-64.14) 0.26 0.02 1 per day 85/84/85 64.22 (63.85-64.59) 64.65 (64.23-65.08) 63.77 (63.30-64.24) ≥2 per day 165/165/163 64.40 (63.69-65.10) 64.61 (63.80-65.42) 64.19 (63.45-64.95) Race White 325/324/324 64.27 (63.99-64.55) 0.10 64.82 (64.47-65.16) 0.43 63.72 (63.41-64.04) 0.02 0.19 Black 22/22/21 64.03 (63.44-64.61) 64.84 (63.94-65.75) 63.21 (62.43-63.98) Hispanic 22/22/22 65.40 (63.85-66.96) 65.38 (63.47-67.28) 65.43 (63.81-67.05) Other 19/19/19 65.43 (63.61-67.25) 65.52 (63.48-67.55) 65.35 (63.56-67.13) - Table 3.
Association between LINE-1 methylation and dietary intake of B-vitamin and multivitamin use
Counts* Overall Left side Right side P† NT/NL/NR Mean (95% CI) P‡ Mean (95% CI) P‡ Mean (95% CI) P‡ Dietary folate (μg/d) Q1 (78.08-205.86) 94/94/93 64.66 (64.09-65.23) 0.02 64.85 (64.18-65.51) 0.32 64.47 (63.83-65.11) <0.01 0.10 Q2 (206.87-277.3) 94/94/94 64.82 (64.69-65.32) 65.47 (64.79-66.16) 64.16 (63.59-64.73) Q3 (277.31-373.65) 94/94/93 64.05 (63.55-64.56) 64.57 (63.95-65.19) 63.53 (62.94-64.12) Q4 (376.17-1,285.59) 93/91/92 63.92 (63.36-64.48) 64.63 (63.96-65.31) 63.22 (62.61-63.82) Dietary B2 (mg/d) Q1 (0.39-1.18) 98/98/97 64.73 (64.18-65.28) 0.57 65.22 (64.52-65.92) 0.75 64.24 (63.67-64.82) 0.16 0.12 Q2 (1.19-1.57) 92/92/92 64.17 (63.64-64.70) 64.36 (63.73-65.00) 63.97 (63.33-64.61) Q3 (1.60-2.20) 92/92/92 64.03 (63.56-64.48) 64.66 (64.03-65.30) 63.39 (62.89-63.89) Q4 (2.21-6.56) 93/91/91 64.53 (63.93-65.13) 65.29 (64.62-65.96) 63.77 (63.09-64.45) Dietary B6 (mg/d) Q1 (0.33-1.08) 99/99/99 64.72 (64.17-65.28) 0.17 64.99 (64.31-65.66) 0.77 64.46 (63.87-65.04) 0.04 0.32 Q2 (1.09-1.54) 89/89/88 64.23 (63.68-64.78) 64.76 (64.13-65.39) 63.70 (63.05-64.35) Q3 (1.55-2.00) 95/95/94 64.38 (63.90-64.86) 65.02 (64.32-65.71) 63.76 (63.25-64.27) Q4 (2.01-6.20) 92/90/91 64.11 (63.56-64.65) 64.76 (64.12-65.39) 63.45 (62.80-64.11) Multivitamin use No 256/255/253 64.22 (63.90-64.53) 0.12 64.72 (64.31-65.13) 0.18 63.71 (63.35-64.06) 0.10 0.97 Yes 130/130/130 64.67 (64.20-65.13) 65.19 (64.65-65.72) 64.15 (63.61-64.70) NOTE: Quartiles of the residuals of the regression of the logarithm of the nutrient on the logarithm of kilocalories. Means are adjusted for energy intake using the logarithm of caloric intake. Quartiles ranges are based in a 2,000 calories/d diet.
↵* NT = total individuals; NL = total individuals with samples on the left side; NR = total individuals with samples on the right side.
↵† Pinteraction testing differences between right and left sides of the colorectum.
↵‡ Ptrend.
- Table 4.
Association between LINE-1 methylation and circulating levels of B vitamins and homocysteine
Counts* Overall Left side Right side P† NT/NL/NR Mean (95% CI) P‡ Mean (95% CI) P‡ Mean (95% CI) P‡ Plasma folate (nmol/L) Q1 (3.14-10.02) 93/93/91 64.80 (64.32-65.28) 0.22 65.33 (64.69-65.97) 0.43 64.26 (63.69-64.84) 0.22 0.88 Q2 (10.05-16.70) 92/92/92 64.12 (63.53-64.70) 64.52 (63.80-65.24) 63.71 (63.09-64.33) Q3 (16.73-27.26) 93/92/92 64.20 (63.66-64.73) 64.70 (64.01-65.39) 63.71 (63.08-64.34) Q4 (27.31-119.0) 92/92/92 64.30 (63.77-64.83) 64.88 (64.26-65.50) 63.72 (63.13-64.31) RBC folate (ng/mL) Q1 (64.86-303.0) 98/98/96 64.07 (63.69-64.46) 0.99 64.41 (63.89-64.93) 0.66 63.72 (63.23-64.22) 0.66 0.68 Q2 (304.0-383.0) 96/96/95 64.58 (63.94-65.21) 65.13 (64.37-65.90) 64.02 (63.30-64.73) Q3 (384.0-468.0) 98/97/98 64.92 (64.32-65.53) 65.55 (64.83-66.26) 64.30 (63.64-64.95) Q4 (469.0-952.0) 95/94/95 63.95 (63.50-64.41) 64.47 (63.88-65.06) 63.45 (62.94-63.96) Plasma B2 (nmol/L) Q1 (2.54-8.93) 93/92/91 64.62 (63.99-65.24) 0.45 64.81 (64.11-65.52) 0.71 64.42 (63.68-65.17) 0.08 0.17 Q2 (9.10-14.70) 93/93/92 64.31 (63.75-64.86) 64.88 (64.22-65.55) 63.72 (63.06-64.38) Q3 (14.90-23.70) 93/92/93 64.18 (63.73-64.64) 64.67 (64.07-65.27) 63.71 (63.19-64.22) Q4 (23.80-468.5) 92/92/92 64.34 (63.83-64.84) 65.08 (64.38-65.79) 63.59 (63.11-64.07) Plasma B6 (nmol/L) Q1 (9.74-36.0) 94/94/92 64.27 (63.69-64.84) 0.29 64.38 (63.71-65.06) 0.04 64.15 (63.44-64.84) 0.76 0.11 Q2 (36.1-51.2) 93/92/92 64.08 (63.51-64.65) 64.69 (63.96-65.42) 63.47 (62.88-64.06) Q3 (52.1-79.8) 92/91/92 64.57 (64.06-65.08) 65.14 (64.51-65.77) 64.00 (63.40-64.60) Q4 (80.7-857) 92/92/92 64.53 (64.07-65.00) 65.25 (64.63-65.86) 63.83 (63.32-64.34) Plasma B12 (pmol/L) Q1 (43.90-240.7) 93/92/91 64.34 (63.69-64.99) 0.58 64.68 (63.91-65.45) 0.85 63.99 (63.29-64.69) 0.45 0.75 Q2 (242.7-307.1) 93/93/93 64.62 (64.04-65.19) 65.25 (64.47-66.04) 63.98 (63.37-64.59) Q3 (307.7-400.8) 93/92/93 64.26 (63.83-64.69) 64.77 (64.22-65.31) 63.75 (63.20-64.30) Q4 (400.9-2072) 93/93/92 64.23 (63.78-64.67) 64.75 (64.22-65.27) 63.71 (63.16-64.26) Homocysteine (μmol/L) Q1 (4.73-7.92) 93/93/92 64.23 (63.72-64.74) 0.86 64.89 (64.29-65.48) 0.82 63.58 (63.03-64.13) 0.56 0.70 Q2 (7.94-9.25) 93/93/93 64.35 (63.85-64.85) 64.77 (64.07-65.46) 63.94 (63.93-64.49) Q3 (9.29-11.10) 93/91/92 64.62 (64.08-65.17) 65.14 (64.57-65.71) 64.11 (63.38-64.83) Q4 (11.18-23.30) 92/92/91 64.21 (63.62-64.79) 64.64 (63.85-65.44) 63.78 (63.22-64.33) - Table 5.
Association between LINE-1 methylation and selected polymorphisms
Counts* Overall Left side Right side P† NT/NL/NR Mean (95% CI) P‡ Mean (95% CI) P‡ Mean (95% CI) P‡ MTHFR-C677T CC 156/156/156 64.44 (64.02-64.86) 0.53 65.05 (64.54-65.56) 0.89 63.84 (63.34-64.34) 0.32 0.26 CT 156/156/155 64.25 (63.85-64.65) 64.65 (64.14-65.16) 63.86 (63.42-64.29) TT 45/44/43 64.16 (63.38-64.94) 64.97 (63.98-65.95) 63.36 (62.56-64.16) MTHFR-A1298C AA 174/173/172 64.04 (63.69-64.39) 0.44 64.57 (64.16-64.98) 0.30 63.52 (63.10-63.95) 0.87 0.65 AC 142/142/141 64.64 (64.18-65.10) 65.12 (64.51-65.72) 64.16 (63.68-64.65) CC 39/39/39 64.42 (63.52-65.33) 65.21 (64.05-66.37) 63.62 (62.59-64.64) MTR-A2756G AA 244/244/243 64.28 (63.95-64.61) 0.39 64.78 (64.37-65.20) 0.36 63.77 (63.41-64.14) 0.88 0.72 AG 101/100/99 64.39 (63.87-64.91) 64.95 (64.33-65.58) 63.82 (63.22-64.43) GG 12/12/12 64.72 (63.78-65.67) 65.60 (63.91-67.29) 63.84 (63.07-64.61) MTRR-A66G AA 88/88/86 64.59 (64.06-65.13) 0.48 65.43 (64.75-66.11) 0.13 63.76 (63.15-64.36) 0.68 0.14 AG 168/168/168 64.19 (63.79-64.59) 64.64 (64.14-65.15) 63.74 (63.29-64.19) GG 99/98/98 64.33 (63.82-64.83) 64.72 (64.11-65.33) 63.93 (63.35-64.52) CBS-C1080T CC 169/168/168 64.22 (63.81-64.62) 0.86 64.84 (64.35-65.32) 0.70 63.60 (63.12-64.07) 0.44 0.55 CT 150/150/148 64.46 (64.04-64.88) 64.93 (64.39-65.48) 63.98 (63.53-64.42) TT 36/36/36 64.30 (63.53-65.06) 64.61 (63.59-65.64) 63.98 (63.15-64.81) CBS-C699T CC 153/153/151 64.49 (64.07-64.91) 0.74 64.88 (64.34-65.41) 0.47 64.10 (63.65-64.55) 0.82 0.37 CT 170/169/169 64.12 (63.73-64.50) 64.75 (64.27-65.22) 63.49 (63.05-63.93) TT 33/33/33 64.66 (63.80-65.51) 64.33 (64.21-66.45) 63.96 (62.84-65.09)