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1Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea
2Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
3Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
© 2024, Korean Society of Epidemiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Characteristics | Total (n=4,260) |
Male (n=2,748) |
Female (n=1,512) |
||||||
---|---|---|---|---|---|---|---|---|---|
Control (n=2,840) | Case (n=1,420) | p-value |
Control (n=1,832) | Case (n=916) | p-value |
Control (n=1,008) | Case (n=504) | p-value |
|
Age (yr) | 57.61±9.48 | 58.13±10.25 | 0.110 | 57.90±9.06 | 58.51±9.95 | 0.120 | 57.08±10.18 | 57.44±10.76 | 0.530 |
Sex | |||||||||
Male | 1,832 (64.5) | 916 (64.5) | - | - | - | - | |||
Female | 1,008 (35.5) | 504 (35.5) | - | - | - | - | |||
Body mass index (kg/m2) | 24.06±2.83 | 24.08±3.41 | 0.870 | 24.44±2.78 | 24.09±3.11 | 0.004 | 23.36±2.80 | 24.06±3.90 | <0.001 |
<18.5 | 38 (1.3) | 48 (3.4) | 0.003 | 15 (0.8) | 27 (3.0) | <0.001 | 23 (2.3) | 21 (4.2) | <0.001 |
18.5-<23.0 | 957 (33.7) | 528 (37.2) | 515 (28.1) | 323 (35.3) | 442 (43.9) | 205 (40.7) | |||
23.0-<25.0 | 848 (30.0) | 335 (23.6) | 569 (31.1) | 233 (25.4) | 279 (27.7) | 102 (20.2) | |||
≥25.0 | 942 (33.2) | 509 (35.9) | 707 (38.6) | 333 (36.4) | 235 (23.3) | 176 (34.9) | |||
Missing | 55 (1.9) | 0 (0.0) | 26 (1.4) | 0 (0.0) | 29 (2.9) | 0 (0.0) | |||
Family history of CRC | <0.001 | <0.001 | 0.230 | ||||||
Yes | 135 (4.8) | 122 (8.6) | 78 (4.3) | 83 (9.1) | 57 (5.7) | 39 (7.7) | |||
No | 2,701 (95.1) | 1,298 (91.4) | 1,751 (95.6) | 833 (90.9) | 950 (94.3) | 465 (92.3) | |||
Missing | 4 (0.1) | 0 (0.0) | 3 (0.2) | 0 (0.0) | 1 (0.1) | 0 (0.0) | |||
Supplement use | <0.001 | <0.001 | <0.001 | ||||||
Yes | 2,116 (74.5) | 789 (55.6) | 1,315 (71.8) | 501 (54.7) | 801 (79.5) | 288 (57.1) | |||
No | 685 (24.1) | 627 (44.2) | 495 (27.0) | 414 (45.2) | 190 (18.9) | 213 (42.3) | |||
Missing | 39 (1.4) | 4 (0.3) | 22 (1.2) | 1 (0.1) | 17 (1.7) | 3 (0.6) | |||
Marital status | 0.009 | 0.180 | 0.020 | ||||||
Married | 2,404 (84.7) | 1,243 (87.5) | 1,637 (89.4) | 830 (90.6) | 767 (76.1) | 413 (81.9) | |||
Single | 83 (2.9) | 29 (2.0) | 40 (2.2) | 19 (2.1) | 43 (4.3) | 10 (2.0) | |||
Divorced, widowed, other | 327 (11.5) | 147 (10.4) | 142 (7.8) | 67 (7.3) | 185 (18.4) | 80 (15.9) | |||
Missing | 26 (0.9) | 1 (0.1) | 13 (0.7) | 0 (0.0) | 13 (2.3) | 1 (0.2) | |||
Education | <0.001 | <0.001 | <0.001 | ||||||
≤Elementary school | 174 (6.1) | 253 (17.8) | 77 (4.2) | 114 (12.5) | 97 (9.6) | 139 (27.6) | |||
Middle school | 205 (7.2) | 204 (14.4) | 127 (6.9) | 135 (14.7) | 78 (7.7) | 69 (13.7) | |||
High school | 1,184 (41.7) | 592 (41.7) | 710 (38.8) | 395 (43.1) | 474 (47.0) | 197 (39.1) | |||
≥College | 1,236 (43.5) | 369 (26.0) | 886 (48.4) | 272 (29.7) | 350 (34.7) | 97 (19.3) | |||
Missing | 41 (1.4) | 2 (0.1) | 32 (1.8) | 0 (0.0) | 9 (0.9) | 2 (0.4) | |||
Monthly income (10,000 KRW/mo) | <0.001 | <0.001 | <0.001 | ||||||
<200 | 652 (23.0) | 561 (39.5) | 365 (19.9) | 359 (39.2) | 287 (28.5) | 202 (40.1) | |||
200-400 | 1,075 (37.9) | 518 (36.5) | 718 (39.2) | 330 (36.0) | 357 (35.4) | 188 (37.3) | |||
≥400 | 1,025 (36.1) | 328 (23.1) | 693 (37.8) | 220 (24.0) | 332 (32.9) | 108 (21.4) | |||
Missing | 88 (3.1) | 13 (0.9) | 56 (3.1) | 7 (0.8) | 32 (3.2) | 6 (1.2) | |||
Occupation | <0.001 | <0.001 | 0.070 | ||||||
Housewife | 582 (20.5) | 303 (21.3) | 5 (0.3) | 1 (0.1) | 577 (57.2) | 302 (59.9) | |||
Professional, office worker | 792 (27.9) | 332 (23.4) | 604 (33.0) | 268 (29.3) | 188 (18.7) | 64 (12.7) | |||
Sales, service | 574 (20.2) | 90 (6.3) | 437 (23.9) | 60 (6.6) | 137 (13.6) | 30 (6.0) | |||
Agriculture, laborer, unemployed, other | 862 (30.4) | 694 (48.9) | 764 (41.7) | 587 (64.1) | 98 (9.7) | 107 (21.2) | |||
Missing | 30 (1.1) | 1 (0.1) | 22 (1.2) | 0 (0.0) | 8 (0.8) | 1 (0.2) | |||
Smoking status | 0.230 | 0.020 | 0.070 | ||||||
Current | 471 (16.6) | 230 (16.2) | 446 (24.3) | 210 (22.9) | 25 (2.5) | 20 (4.0) | |||
Former | 1,058 (37.3) | 500 (35.2) | 1,014 (55.4) | 472 (51.5) | 44 (4.4) | 28 (5.6) | |||
Never | 1,311 (46.2) | 689 (48.5) | 372 (20.3) | 234 (25.6) | 939 (93.2) | 455 (90.3) | |||
Missing | 0 (0.0) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.2) | |||
Alcohol consumption | <0.001 | <0.001 | <0.001 | ||||||
Current | 1,710 (60.2) | 685 (48.2) | 1,299 (70.9) | 551 (60.2) | 411 (40.8) | 134 (26.6) | |||
Former | 272 (9.6) | 204 (14.4) | 227 (12.4) | 161 (17.6) | 45 (4.5) | 43 (8.5) | |||
Never | 858 (30.2) | 530 (37.3) | 306 (16.7) | 204 (22.3) | 552 (54.8) | 326 (64.7) | |||
Missing | 0 (0.0) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.2) | |||
Regular exercise | <0.001 | <0.001 | <0.001 | ||||||
Yes | 1,589 (56.0) | 504 (35.5) | 1,070 (58.4) | 344 (37.6) | 519 (51.5) | 160 (31.8) | |||
No | 1,101 (38.8) | 916 (64.5) | 732 (40.0) | 572 (62.5) | 369 (36.6) | 344 (68.3) | |||
Missing | 150 (5.3) | 0 (0.0) | 30 (1.6) | 0 (0.0) | 120 (11.9) | 0 (0.0) | |||
Physical activity (MET-min/wk) | 2,627.4±2,781.1 | 2,145.9±1,999.8 | <0.001 | 2,918.4±2,925.4 | 2,327.5±2,094.9 | <0.001 | 2,098.8±2,410.7 | 1,816.5±1,769.6 | 0.010 |
Red meat intake (g/day) |
55.64±40.08 | 47.62±35.14 | <0.001 | 57.94±42.09 | 50.82±37.35 | <0.001 | 51.46±35.77 | 41.81±29.88 | <0.001 |
Variables | Total |
Male |
Female |
||||||
---|---|---|---|---|---|---|---|---|---|
Controls (n=2,840) | Cases (n=1,420) | p-value |
Controls (n=1,832) | Cases (n=916) | p-value |
Controls (n=1,008) | Cases (n=504) | p-value |
|
Total energy intake (kcal/day) | 1,741.1±567.0 | 2,043.6±575.2 | <0.001 | 1,785.1±547.8 | 2,162.6±542.5 | <0.001 | 1,661.1±592.4 | 1,827.3±570.4 | <0.001 |
Vitamin B2 (mg/day) | 1.21±0.38 | 1.12±0.33 | <0.001 | 1.15±0.35 | 1.07±0.31 | <0.001 | 1.32±0.41 | 1.19±0.35 | <0.001 |
Vitamin B2 | CRC |
Proximal colon cancer |
Distal colon cancer (mg/day) |
Rectal cancer |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Controls | Cases | Model I | Model II | Cases | Model I | Model II | Cases | Model I | Model II | Cases | Model I | Model II | |
Total | |||||||||||||
Q1 (<0.94) | 710 (25.0) | 464 (32.7) | 1.00 (reference) | 1.00 (reference) | 122 (27.7) | 1.00 (reference) | 1.00 (reference) | 140 (30.8) | 1.00 (reference) | 1.00 (reference) | 189 (37.4) | 1.00 (reference) | 1.00 (reference) |
Q2 (0.94-1.17) | 710 (25.0) | 446 (31.4) | 0.96 (0.81, 1.14) | 1.01 (0.82, 1.23) | 136 (30.9) | 1.12 (0.86, 1.45) | 1.15 (0.86, 1.53) | 141 (31.1) | 1.01 (0.78, 1.30) | 1.04 (0.79, 1.38) | 165 (32.7) | 0.87 (0.69, 1.10) | 0.94 (0.71, 1.23) |
Q3 (1.17-1.43) | 710 (25.0) | 296 (20.9) | 0.64 (0.53, 0.76) | 0.69 (0.55, 0.86) | 99 (22.5) | 0.81 (0.61, 1.08) | 0.84 (0.61, 1.15) | 91 (20.0) | 0.65 (0.49, 0.71) | 0.66 (0.48, 0.91) | 103 (20.4) | 0.55 (0.42, 0.71) | 0.63 (0.46, 0.85) |
Q4 (≥1.43) | 710 (25.0) | 214 (15.1) | 0.46 (0.38, 0.56) | 0.65 (0.51, 0.82) | 83 (18.9) | 0.68 (0.51, 0.92) | 0.87 (0.62, 1.23) | 82 (18.1) | 0.59 (0.44, 0.78) | 0.76 (0.54, 1.06) | 48 (9.5) | 0.25 (0.18, 0.36) | 0.40 (0.27, 0.58) |
p for trend | <0.001 | <0.001 | 0.002 | 0.193 | <0.001 | 0.020 | <0.001 | <0.001 | |||||
Male | |||||||||||||
Q1 (<0.90) | 458 (25.0) | 278 (31.4) | 1.00 (reference) | 1.00 (reference) | 62 (22.9) | 1.00 (reference) | 1.00 (reference) | 79 (28.4) | 1.00 (reference) | 1.00 (reference) | 129 (36.5) | 1.00 (reference) | 1.00 (reference) |
Q2 (0.90-1.11) | 458 (25.0) | 312 (34.1) | 1.12 (0.91, 1.38) | 1.13 (0.88, 1.45) | 95 (35.1) | 1.53 (1.08, 2.16) | 1.54 (1.06, 2.25) | 99 (35.6) | 1.25 (0.91, 1.73) | 1.22 (0.86, 1.74) | 115 (32.6) | 0.89 (0.67, 1.18) | 0.87 (0.63, 1.21) |
Q3 (1.11-1.36) | 458 (25.0) | 185 (20.2) | 0.67 (0.53, 0.84) | 0.70 (0.53, 0.92) | 57 (21.0) | 0.92 (0.63, 1.35) | 0.95 (0.63, 1.45) | 55 (19.8) | 0.70 (0.48, 1.01) | 0.77 (0.45, 1.00) | 71 (20.1) | 0.55 (0.40, 0.76) | 0.60 (0.41, 0.86) |
Q4 (≥1.36) | 458 (25.0) | 141 (15.4) | 0.51 (0.40, 0.65) | 0.60 (0.45, 0.82) | 57 (21.0) | 0.92 (0.63, 1.35) | 1.06 (0.68, 1.64) | 45 (16.2) | 0.57 (0.39, 0.84) | 0.60 (0.39, 0.93) | 38 (10.8) | 0.30 (0.20, 0.43) | 0.40 (0.23, 0.58) |
p for trend | <0.001 | <0.001 | 0.190 | 0.730 | <0.001 | 0.008 | <0.001 | <0.001 | |||||
Female | |||||||||||||
Q1 (<1.03) | 252 (25.0) | 177 (35.1) | 1.00 (reference) | 1.00 (reference) | 57 (33.7) | 1.00 (reference) | 1.00 (reference) | 55 (31.3) | 1.00 (reference) | 1.00 (reference) | 60 (39.5) | 1.00 (reference) | 1.00 (reference) |
Q2 (1.03-1.30) | 252 (25.0) | 166 (32.9) | 0.94 (0.71, 1.23) | 0.98 (0.70, 1.38) | 53 (31.4) | 0.93 (0.62, 1.41) | 0.98 (0.62, 1.56) | 58 (33.0) | 1.06 (0.70, 1.59) | 1.11 (0.70, 1.78) | 53 (34.9) | 0.88 (0.59, 1.33) | 0.90 (0.56, 1.44) |
Q3 (1.30-1.60) | 252 (25.0) | 101 (20.0) | 0.57 (0.42, 0.77) | 0.79 (0.54, 1.14) | 32 (18.9) | 0.56 (0.35, 0.89) | 0.78 (0.46, 1.31) | 39 (22.2) | 0.71 (0.45, 1.11) | 0.97 (0.58, 1.63) | 30 (19.7) | 0.50 (0.31, 0.80) | 0.67 (0.39, 1.16) |
Q4 (≥1.60) | 252 (25.0) | 60 (11.9) | 0.34 (0.24, 0.48) | 0.60 (0.40, 0.90) | 27 (16.0) | 0.47 (0.29, 0.77) | 0.71 (0.41, 1.24) | 24 (13.6) | 0.44 (0.26, 0.73) | 0.80 (0.45, 1.44) | 9 (5.9) | 0.15 (0.07, 0.31) | 0.27 (0.12, 0.60) |
p for trend | <0.001 | 0.008 | <0.001 | 0.146 | <0.001 | 0.404 | <0.001 | <0.001 |
Vitamin B2 intake (mg/day) | A/A |
G/A+G/G |
p for interaction |
||||||
---|---|---|---|---|---|---|---|---|---|
Q1 | Q2 | Q3 | Q4 | Q1 | Q2 | Q3 | Q4 | ||
MTRR rs1801394 | |||||||||
All | <0.98 | 0.98-1.20 | 1.20-1.46 | ≥1.46 | <0.98 | 0.98-1.20 | 1.20-1.46 | ≥1.46 | |
No. of controls/cases | 145/200 | 146/177 | 138/103 | 147/79 | 125/185 | 124/153 | 133/98 | 123/86 | |
Model I | 1.00 (reference) | 0.86 (0.63, 1.18) | 0.52 (0.37, 0.73) | 0.37 (0.26, 0.53) | 1.04 (0.76, 1.44) | 0.86 (0.62, 1.18) | 0.51 (0.36, 0.73) | 0.47 (0.33, 0.68) | 0.57 |
Model II | 1.00 (reference) | 0.56 (0.35, 0.88) | 0.56 (0.33, 0.93) | 0.72 (0.42, 1.22) | 1.30 (0.82, 2.07) | 1.49 (0.92, 2.40) | 0.76 (0.45, 1.26) | 1.05 (0.60, 1.83) | 0.43 |
Male | <0.94 | 0.94-1.15 | 1.15-1.38 | ≥1.38 | <0.94 | 0.94-1.15 | 1.15-1.38 | ≥1.38 | |
No. of controls/cases | 83/132 | 97/111 | 94/70 | 99/48 | 86/112 | 73/102 | 75/56 | 70/60 | |
Model I | 1.00 (reference) | 0.72 (0.49, 1.06) | 0.47 (0.31, 0.71) | 0.31 (0.20, 0.47) | 0.82 (0.55, 1.21) | 0.88 (0.59, 1.32) | 0.47 (0.30, 0.73) | 0.54 (0.35, 0.84) | 0.04 |
Model II | 1.00 (reference) | 0.57 (0.36, 0.92) | 0.47 (0.29, 0.79) | 0.31 (0.18, 0.54) | 0.73 (0.45, 1.18) | 0.87 (0.52, 1.44) | 0.51 (0.30, 0.86) | 0.62 (0.36, 1.08) | 0.02 |
Female | <1.05 | 1.05-1.32 | 1.32-1.61 | ≥1.61 | <1.05 | 1.05-1.32 | 1.32-1.61 | ≥1.61 | |
No. of controls/cases | 60/75 | 50/61 | 42/40 | 51/22 | 41/68 | 51/66 | 59/32 | 50/26 | |
Model I | 1.00 (reference) | 0.98 (0.59, 1.62) | 0.76 (0.44, 1.32) | 0.35 (0.19, 0.63) | 1.33 (0.79, 2.22) | 1.04 (0.63, 1.71) | 0.43 (0.25, 0.75) | 0.42 (0.23, 0.75) | 0.62 |
Model II | 1.00 (reference) | 1.57 (0.83, 2.98) | 2.00 (0.96, 4.15) | 1.05 (0.48, 2.34) | 1.49 (0.77, 2.89) | 1.86 (0.99, 3.52) | 1.13 (0.56, 2.28) | 1.21 (0.57, 2.55) | 0.44 |
MTR rs1805087 | |||||||||
All | <0.98 | 0.98-1.20 | 1.20-1.46 | ≥1.46 | <0.98 | 0.98-1.20 | 1.20-1.46 | ≥1.46 | |
No. of controls/cases | 192/286 | 199/255 | 204/140 | 219/126 | 78/99 | 71/75 | 67/61 | 51/39 | |
Model I | 1.00 (reference) | 0.86 (0.66, 1.12) | 0.46 (0.34, 0.60) | 0.37 (0.27, 0.50) | 0.86 (0.61, 1.22) | 0.68 (0.47, 0.99) | 0.61 (0.41, 0.91) | 0.48 (0.30, 0.78) | 0.12 |
Model II | 1.00 (reference) | 0.74 (0.50, 1.08) | 0.42 (0.27, 0.66) | 0.72 (0.46, 1.13) | 0.78 (0.45, 1.35) | 0.54 (0.30, 0.98) | 0.93 (0.52, 1.65) | 0.78 (0.37, 1.65) | 0.42 |
Male | <0.94 | 0.94-1.15 | 1.15-1.38 | ≥1.38 | <0.94 | 0.94-1.15 | 1.15-1.38 | ≥1.38 | |
No. of controls/cases | 115/184 | 121/161 | 133/85 | 142/85 | 54/60 | 49/52 | 36/41 | 27/23 | |
Model I | 1.00 (reference) | 0.83 (0.60, 1.16) | 0.40 (0.28, 0.57) | 0.37 (0.26, 0.53) | 0.69 (0.45, 1.07) | 0.66 (0.42, 1.05) | 0.71 (0.43, 1.17) | 0.53 (0.29, 0.97) | 0.02 |
Model II | 1.00 (reference) | 0.75 (0.50, 1.13) | 0.38 (0.25, 0.60) | 0.39 (0.25, 0.60) | 0.52 (0.30, 0.87) | 0.47 (0.27, 0.83) | 0.82 (0.45, 1.50) | 0.65 (0.30, 1.40) | <0.001 |
Female | <1.05 | 1.05-1.32 | 1.32-1.61 | ≥1.61 | <1.05 | 1.05-1.32 | 1.32-1.61 | ≥1.61 | |
No. of controls/cases | 79/106 | 73/95 | 70/57 | 81/34 | 22/37 | 28/32 | 31/15 | 20/14 | |
Model I | 1.00 (reference) | 0.97 (0.64, 1.48) | 0.61 (0.39, 0.96) | 0.31 (0.19, 0.51) | 1.25 (0.69, 2.29) | 0.85 (0.48, 1.53) | 0.36 (0.18, 0.71) | 0.52 (0.25, 1.10) | 0.94 |
Model II | 1.00 (reference) | 1.69 (0.98, 2.91) | 1.61 (0.87, 2.97) | 0.87 (0.46, 1.67) | 1.21 (0.57, 2.57) | 1.12 (0.54, 2.33) | 0.82 (0.36, 1.87) | 1.44 (0.56, 3.74) | >0.99 |
Values are presented as mean±standard deviation or number (%). CRC, colorectal cancer; KRW, Korean won; MET, metabolic equivalent of task. Using the chi-square and Student t-test for continuous and categorical variables, respectively. Red meat intake was adjusted for total energy intake using residual method.
Values are presented as mean±standard deviation. Using the Student t-test.
Values are presented as number (%) or odds ratio (95% confidence interval). Model I: Crude model; Model II: Adjusted for age, sex, body mass index, alcohol consumption, smoking status, marital status, occupation, education, family history of CRC, supplement use, monthly income, regular exercise, red meat intake, and total energy intake; The sex variable was excluded for the male and female groups.
Values are presented as odds ratio (95% confidence interval). Model I: Crude model; Model II: Adjusted for age, sex, body mass index, alcohol consumption, smoking status, marital status, occupation, education, family history of CRC, supplement use, monthly income, regular exercise, red meat intake, and total energy intake; The sex variable was excluded for the male and female groups. False discovery rate–adjusted p-values.