TABLE 2.
Baseline alcohol intake and risk of colorectal cancer according to IGF2 DMR0 methylation level1
| Alcohol intake, g/d |
|||||
| 0 | 1–14 | ≥15 | P-trend2 | P-heterogeneity3 | |
| Person-years | 946,353 | 1,765,554 | 495,078 | — | — |
| All colorectal cancers | — | ||||
| Cases, n | 258 | 523 | 212 | — | |
| Age-adjusted HR (95% CI) | 1 (referent) | 1.10 (0.95, 1.28) | 1.32 (1.10, 1.59) | 0.006 | |
| Multivariable-adjusted HR (95% CI) | 1 (referent) | 1.13 (0.97, 1.32) | 1.28 (1.05, 1.55) | 0.043 | |
| IGF2 DMR0 methylation level | 0.006 | ||||
| First quartile (≤25%) | |||||
| Cases, n | 63 | 125 | 59 | — | |
| Age-adjusted HR (95% CI) | 1 (referent) | 1.08 (0.80, 1.46) | 1.60 (1.12, 2.29) | 0.003 | |
| Multivariable-adjusted HR (95% CI) | 1 (referent) | 1.11 (0.82, 1.50) | 1.55 (1.08, 2.24) | 0.009 | |
| Second quartile (26–50%) | |||||
| Cases, n | 51 | 138 | 63 | — | |
| Age-adjusted HR (95% CI) | 1 (referent) | 1.49 (1.08, 2.06) | 2.15 (1.48, 3.12) | 0.0001 | |
| Multivariable-adjusted HR (95% CI) | 1 (referent) | 1.55 (1.12, 2.14) | 2.11 (1.44, 3.07) | 0.0004 | |
| Third quartile (51–75%) | |||||
| Cases, n | 72 | 123 | 53 | — | |
| Age-adjusted HR (95% CI) | 1 (referent) | 0.94 (0.70, 1.25) | 1.27 (0.89, 1.82) | 0.080 | |
| Multivariable-adjusted HR (95% CI) | 1 (referent) | 0.96 (0.71, 1.28) | 1.22 (0.85, 1.76) | 0.15 | |
| Fourth quartile (>75%) | |||||
| Cases, n | 72 | 137 | 37 | — | |
| Age-adjusted HR (95% CI) | 1 (referent) | 1.05 (0.79, 1.40) | 0.86 (0.58, 1.29) | 0.33 | |
| Multivariable-adjusted HR (95% CI) | 1 (referent) | 1.08 (0.81, 1.44) | 0.84 (0.56, 1.26) | 0.24 | |
Cox proportional cause-specific hazards regression for competing risk data were used to compute HRs and 95% CIs. All analyses were stratified by age (in mo), year of questionnaire return, and sex. Multivariable-adjusted HRs were further adjusted for BMI (in kg/m2; <25 compared with 25–29.9 compared with ≥30), pack-years smoked (0 compared with 1–19 compared with 20–39 compared with ≥40 pack-years), family history of colorectal cancer in any first-degree relative, endoscopy status (no endoscopy compared with history of adenomatous polyps compared with negative endoscopy), physical activity level (quintiles of mean metabolic equivalent task-hours per week), red meat intake (quintiles of servings/d), total calorie intake (quintiles of kcal/d), calcium intake (quintiles of mg/d), current multivitamin use, regular aspirin use, and intakes of vitamin B-6, vitamin B-12, folate, and methionine. DMR0, differentially methylated region-0; IGF2, insulin-like growth factor 2.
Linear trend test by using the median value of each category.
Test for the heterogeneity of the association between alcohol intake and colorectal cancer risk according to IGF2 DMR0 methylation level.