Table 2. Relative risk of folate intake and colon cancer according to microsatellite instability (MSI) status and KRAS mutation among 88,691 women from the Nurses' Health Study (NHS) and 47,371 men from the Health Professionals Follow-up Study (HPFS).
| Energy-adjusted Folate Intake, μg/day | P trend | ||||
|---|---|---|---|---|---|
| <200 | 200-300 | 301-400 | >400 | ||
| All cancer cases | |||||
| No. cases / Person-years | 114 / 461476 | 182 / 757168 | 139 / 473380 | 231 / 874861 | |
| Age-adjusted RR (95% CI) | 1.0 | 0.82 (0.65-1.03) | 0.84 (0.66-1.08) | 0.76 (0.60-0.95) | 0.03 |
| Multivariate RR (95% CI)* | 1.0 | 0.80 (0.63-1.01) | 0.80 (0.61-1.04) | 0.75 (0.58-0.96) | 0.08 |
| MSI-low/MSS cancer cases† | |||||
| No. cases / Person-years | 89 / 461496 | 144 / 757201 | 117 / 473401 | 189 / 874904 | |
| Age-adjusted RR (95% CI) | 1.0 | 1.21 (0.93-1.58) | 0.91 (0.67-1.20) | 0.80 (0.62-1.03) | 0.05 |
| Multivariate RR (95% CI)* | 1.0 | 1.24 (0.95-1.62) | 0.86 (0.64-1.15) | 0.79 (0.60-1.03) | 0.11 |
| MSI-high cancer cases† | |||||
| No. cases / Person-years | 25 / 461549 | 38 / 757294 | 22 / 473478 | 42 / 875029 | |
| Age-adjusted RR (95% CI) | 1.0 | 0.77 (0.47-1.28) | 0.60 (0.34-1.07) | 0.62 (0.38-1.02) | 0.38 |
| Multivariate RR (95% CI)* | 1.0 | 0.75 (0.45-1.01) | 0.57 (0.32-1.01) | 0.61 (0.37-1.02) | 0.45 |
| All cancer cases | |||||
| No. cases / Person-years | 113 / 461476 | 182 / 757197 | 142 / 473402 | 232 / 874893 | |
| Age-adjusted RR (95% CI) | 1.0 | 0.82 (0.65-1.04) | 0.87 (0.68-1.12) | 0.77 (0.61-0.97) | 0.04 |
| Multivariate RR (95% CI)* | 1.0 | 0.81 (0.63-1.02) | 0.82 (0.63-1.07) | 0.76 (0.59-0.97) | 0.08 |
| KRAS-wildtype cancer cases† | |||||
| No. cases / Person-years | 83 / 461503 | 114 / 757261 | 84 / 473452 | 146 / 874968 | |
| Age-adjusted RR (95% CI) | 1.0 | 1.42 (1.07-1.89) | 0.70 (0.52-0.96) | 0.66 (0.50-0.87) | 0.04 |
| Multivariate RR (95% CI)* | 1.0 | 1.45 (1.09-1.93) | 0.67 (0.49-0.92) | 0.66 (0.49-0.87) | 0.06 |
| KRAS-mutated cancer cases† | |||||
| No. cases / Person-years | 30 / 461543 | 68 / 757290 | 58 / 473476 | 86 / 875027 | |
| Age-adjusted RR (95% CI) | 1.0 | 1.16 (0.75-1.78) | 1.33 (0.85-2.06) | 1.06 (0.70-1.62) | 0.46 |
| Multivariate RR (95% CI)* | 1.0 | 1.13 (0.73-1.74) | 1.25 (0.80-1.97) | 1.05 (0.68-1.61) | 0.55 |
*
Multivariate models are adjusted for age (continuous), gender, energy intake (kcal), screening sigmoidoscopy (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).
†
MSI, microsatellite instability; MSS, microsatelllite stable. KRAS mutation in codon 12 or 13.