Table 4.
ORs and 95% CIs for the association of fruits, vegetables, and fiber intake with the risk of molecular subtypes of CRC in case-only analysis, stratified by study design.
| Quartile | |||||
|---|---|---|---|---|---|
| Lowest (Q1) | Second (Q2) | Third (Q3) | Highest (Q4) | Ptrend | |
| Cohort studies | |||||
| Fruits (servings/day) | |||||
| MSI-high vs MSS/MSI-low | |||||
| High (n)/Stable/low cases (n) | 114/591 | 94/500 | 103/505 | 94/502 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.92 (0.67-1.25) | 0.93 (0.69-1.26) | 0.83 (0.60-1.15) | 0.31 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.92 (0.68-1.26) | 0.94 (0.69-1.27) | 0.83 (0.60-1.15) | 0.31 |
| CIMP-positive vs CIMP-negative | |||||
| High (n)/Low cases (n) | 126/575 | 129/479 | 112/512 | 119/495 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.15 (0.86-1.55) | 0.90 (0.66-1.22) | 1.04 (0.76-1.43) | 0.81 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.15 (0.85-1.54) | 0.90 (0.66-1.22) | 1.03 (0.75-1.41) | 0.74 |
| BRAF-mutated vs BRAF-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 109/586 | 86/508 | 100/510 | 90/501 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.88 (0.65-1.22) | 0.99 (0.73-1.35) | 0.96 (0.69-1.34) | 0.97 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.88 (0.64-1.22) | 0.99 (0.72-1.35) | 0.94 (0.67-1.32) | 0.89 |
| KRAS-mutated vs KRAS-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 205/457 | 219/349 | 214/366 | 194/375 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.32 (1.03-1.68) | 1.24 (0.97-1.58) | 1.05 (0.81-1.35) | 0.79 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.31 (1.03-1.66) | 1.22 (0.96-1.56) | 1.02 (0.79-1.32) | 0.93 |
| Vegetables (servings/day) | |||||
| MSI-high vs MSS/MSI-low | |||||
| High (n)/Stable/low cases (n) | 123/603 | 98/516 | 91/538 | 93/440 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.88 (0.65-1.19) | 0.78 (0.57-1.07) | 0.95 (0.69-1.32) | 0.55 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.90 (0.66-1.22) | 0.80 (0.59-1.09) | 0.96 (0.70-1.33) | 0.59 |
| CIMP-positive vs CIMP-negative | |||||
| High (n)/Low cases (n) | 146/573 | 126/505 | 105/528 | 109/454 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.13 (0.84-1.51) | 0.93 (0.68-1.26) | 1.12 (0.82-1.54) | 0.79 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.16 (0.86-1.55) | 0.94 (0.69-1.28) | 1.14 (0.83-1.57) | 0.75 |
| BRAF-mutated vs BRAF-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 114/611 | 106/501 | 86/539 | 79/454 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.24 (0.91-1.68) | 0.94 (0.68-1.29) | 1.00 (0.71-1.41) | 0.65 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.27 (0.94-1.73) | 0.96 (0.69-1.32) | 1.01 (0.71-1.42) | 0.67 |
| KRAS-mutated vs KRAS-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 215/484 | 227/348 | 219/369 | 171/345 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.33 (1.05-1.69) | 1.23 (0.97-1.57) | 1.01 (0.78-1.31) | 0.94 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.34 (1.05-1.70) | 1.23 (0.97-1.57) | 1.00 (0.77-1.30) | 0.99 |
| Fiber (g/day) | |||||
| MSI-high vs MSS/MSI-low | |||||
| High (n)/Stable/low cases (n) | 95/533 | 95/542 | 106/531 | 125/528 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.91 (0.66-1.25) | 1.01 (0.73-1.38) | 1.15 (0.84-1.58) | 0.28 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.92 (0.67-1.27) | 1.05 (0.76-1.44) | 1.19 (0.86-1.65) | 0.20 |
| CIMP-positive vs CIMP-negative | |||||
| High (n)/Low cases (n) | 112/516 | 125/525 | 137/507 | 153/519 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.12 (0.83-1.52) | 1.29 (0.95-1.76) | 1.35 (0.99-1.85) | 0.04 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.13 (0.83-1.53) | 1.33 (0.98-1.81) | 1.35 (0.98-1.85) | 0.04 |
| BRAF-mutated vs BRAF-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 95/544 | 99/535 | 105/527 | 109/536 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.06 (0.77-1.46) | 1.15 (0.83-1.58) | 1.17 (0.84-1.62) | 0.31 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.05 (0.77-1.45) | 1.17 (0.85-1.61) | 1.15 (0.82-1.61) | 0.34 |
| KRAS-mutated vs KRAS-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 200/409 | 206/399 | 200/395 | 228/404 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.03 (0.81-1.32) | 1.00 (0.78-1.29) | 1.14 (0.89-1.47) | 0.35 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.02 (0.80-1.30) | 0.98 (0.76-1.26) | 1.08 (0.84-1.40) | 0.64 |
| Case-control studies | |||||
| Fruits (servings/day) | |||||
| MSI-high vs MSS/MSI-low | |||||
| High (n)/Stable/low cases (n) | 240/1253 | 289/1576 | 219/1196 | 144/836 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.12 (0.94-1.33) | 0.99 (0.84-1.17) | 0.88 (0.73-1.07) | 0.58 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.24 (1.01-1.54) | 1.05 (0.85-1.28) | 0.93 (0.73-1.17) | 0.42 |
| CIMP-positive vs CIMP-negative | |||||
| High (n)/Low cases (n) | 148/718 | 205/1080 | 162/766 | 113/571 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.06 (0.81-1.39) | 1.03 (0.80-1.34) | 0.87 (0.65-1.17) | 0.41 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.08 (0.83-1.42) | 1.10 (0.84-1.43) | 0.96 (0.71-1.29) | 0.89 |
| BRAF-mutated vs BRAF-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 175/1194 | 191/1653 | 154/1181 | 79/835 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.92 (0.71-1.19) | 0.83 (0.65-1.06) | 0.58 (0.43-0.77) | 3.5e-04 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.94 (0.73-1.22) | 0.88 (0.69-1.12) | 0.64 (0.47-0.86) | 4.9e-04 |
| KRAS-mutated vs KRAS-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 297/636 | 484/1061 | 330/704 | 236/478 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.06 (0.87-1.29) | 1.04 (0.85-1.26) | 1.07 (0.87-1.33) | 0.58 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.05 (0.86-1.28) | 1.02 (0.84-1.24) | 1.05 (0.84-1.30) | 0.76 |
| Vegetables (servings/day) | |||||
| MSI-high vs MSS/MSI-low | |||||
| High (n)/Stable/low cases (n) | 144/835 | 372/2019 | 286/1438 | 111/661 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.12 (0.90-1.39) | 1.17 (0.93-1.46) | 0.97 (0.74-1.28) | 0.87 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.12 (0.91-1.39) | 1.19 (0.95-1.50) | 0.98 (0.75-1.30) | 0.75 |
| CIMP-positive vs CIMP-negative | |||||
| High (n)/Low cases (n) | 115/501 | 225/1210 | 189/1001 | 105/467 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.92 (0.70-1.20) | 1.07 (0.81-1.41) | 1.04 (0.75-1.42) | 0.46 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.91 (0.70-1.19) | 1.11 (0.84-1.46) | 1.06 (0.77-1.46) | 0.31 |
| BRAF-mutated vs BRAF-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 89/831 | 256/2044 | 190/1443 | 71/650 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.07 (0.82-1.40) | 1.16 (0.88-1.54) | 0.98 (0.69-1.38) | 0.77 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.07 (0.82-1.40) | 1.21 (0.91-1.60) | 1.00 (0.71-1.41) | 0.58 |
| KRAS-mutated vs KRAS-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 229/490 | 558/1183 | 379/827 | 207/411 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.01 (0.83-1.22) | 0.96 (0.78-1.18) | 1.10 (0.87-1.39) | 0.64 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.00 (0.83-1.21) | 0.95 (0.78-1.17) | 1.09 (0.86-1.38) | 0.70 |
| Fiber (g/day) | |||||
| MSI-high vs MSS/MSI-low | |||||
| High (n)/Stable/low cases (n) | 104/559 | 107/552 | 85/564 | 110/573 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.01 (0.75-1.38) | 0.77 (0.55-1.10) | 0.99 (0.68-1.45) | 0.65 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.03 (0.75-1.39) | 0.80 (0.56-1.13) | 1.02 (0.70-1.51) | 0.79 |
| CIMP-positive vs CIMP-negative | |||||
| High (n)/Low cases (n) | 83/306 | 106/324 | 81/319 | 82/344 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 1.30 (0.92-1.85) | 0.90 (0.61-1.34) | 0.87 (0.55-1.37) | 0.28 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 1.32 (0.93-1.88) | 0.95 (0.64-1.42) | 0.94 (0.60-1.50) | 0.50 |
| BRAF-mutated vs BRAF-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 71/526 | 72/521 | 70/522 | 74/536 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.85 (0.59-1.23) | 0.73 (0.49-1.10) | 0.70 (0.45-1.11) | 0.11 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.88 (0.61-1.27) | 0.80 (0.53-1.21) | 0.80 (0.50-1.28) | 0.33 |
| KRAS-mutated vs KRAS-wildtype | |||||
| Mutated (n)/Wildtype cases (n) | 175/326 | 169/344 | 183/328 | 174/331 | |
| Minimally adjusted OR (95%CI)a | 1.00 (Reference) | 0.93 (0.71-1.21) | 1.08 (0.81-1.45) | 1.03 (0.74-1.44) | 0.66 |
| Multivariate adjusted OR (95%CI)b | 1.00 (Reference) | 0.92 (0.70-1.21) | 1.07 (0.79-1.43) | 1.00 (0.71-1.41) | 0.79 |
a
Minimally adjusted OR was adjusted for age, sex, study, and total energy (continuous).
b
In addition to minimally adjusted OR, multivariate adjusted OR was further adjusted for tobacco smoking (never-, past and current smoker <25, 25-<50, 50-<75, ≥75 pack-years), red meat intake (study- and sex-specific quartiles as continuous), and processed meat intake (study- and sex-specific quartiles as continuous).
Abbreviations: CI: confidence interval; OR: odds ratio.