Table 3.
Exposures related to energy balance in relation to colorectal cancer risk in men and women stratified by genotype strata (dominant model) of SIRT1 variants in the Netherlands Cohort Study (20.3 years of follow-up).
| Men | Women | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BMI | BMI | ||||||||||||||||||||
| T1 sex-specific (13.5–23.9 kg/m2) | T2 sex-specific (23.8–25.9 kg/m2) | T3 sex-specific (25.8–41.3 kg/m2) | P for interaction | T1 sex-specific (14.5–23.5 kg/m2) | T2 sex-specific (23.4–26.2 kg/m2) | T3 sex-specific (26.1–42.2 kg/m2) | P for interaction | ||||||||||||||
| N cases/PT at risk | HRa | (95% CI) | N cases/PT at risk | HRa | (95% CI) | N cases/PT at risk | HRa | (95% CI) | N cases/PT at risk | HRa | (95% CI) | N cases/PT at risk | HRa | (95% CI) | N cases/PT at risk | HRa | (95% CI) | ||||
| rs10997870 | TT | 220/3472 | 1 | (ref.) | 214/3641 | 0.86 | (0.64,1.14) | 276/3454 | 1.15 | (0.87,1.54) | 161/3796 | 1 | (ref.) | 180/3045 | 1.29 | (0.95,1.76) | 142/3140 | 1.02 | (0.74,1.40) | ||
| TG/GG | 296/5466 | 1 | (ref.) | 360/5512 | 1.14 | (0.90,1.43) | 352/4670 | 1.36 | (1.07,1.72) | 0.37 | 268/5240 | 1 | (ref.) | 230/5675 | 0.79 | (0.62,1.01) | 236/5170 | 0.89 | (0.69,1.15) | 0.04b | |
| rs12778366 | TT | 377/6169 | 1 | (ref.) | 420/6782 | 0.97 | (0.78,1.19) | 488/6247 | 1.20 | (0.97,1.48) | 309/6608 | 1 | (ref.) | 317/5989 | 1.09 | (0.87,1.36) | 279/5974 | 0.95 | (0.75,1.20) | ||
| TC/CC | 139/2769 | 1 | (ref.) | 154/2371 | 1.17 | (0.82,1.66) | 140/1877 | 1.47 | (1.01,2.13) | 0.53 | 120/2427 | 1 | (ref.) | 93/2731 | 0.74 | (0.51,1.07) | 99/2322 | 0.97 | (0.65,1.45) | 0.10 | |
| Trouser/skirt size | Trouser/skirt size | ||||||||||||||||||||
| <median | ≥median | P for interaction | <median | ≥median | P for interaction | ||||||||||||||||
| N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | ||||||||||
| rs10997870 | TT | 219/3651 | 1 | (ref.) | 435/6091 | 0.99 | (0.75,1.32) | 209/4593 | 1 | (ref.) | 266/5320 | 1.16 | (0.83,1.60) | ||||||||
| TG/GG | 297/5592 | 1 | (ref.) | 621/8745 | 1.31 | (1.04,1.64) | 0.30 | 313/6850 | 1 | (ref.) | 415/8964 | 1.00 | (0.77,1.30) | 0.55 | |||||||
| rs12778366 | TT | 384/6539 | 1 | (ref.) | 798/11144 | 1.12 | (0.91,1.37) | 384/8290 | 1 | (ref.) | 508/10085 | 1.09 | (0.86,1.39) | ||||||||
| TC/CC | 132/2704 | 1 | (ref.) | 258/3692 | 1.33 | (0.94,1.87) | 0.25 | 138/3153 | 1 | (ref.) | 173/4185 | 0.97 | (0.65,1.43) | 0.38 | |||||||
| BMI @ 20 years | BMI @ 20 years | ||||||||||||||||||||
| T1 sex-specific (11.3–20.8 kg/m 2 ) | T2 sex-specific (20.7–22.7 kg/m 2 ) | T3 sex-specific (22.6–33.1 kg.m 2 ) | P for interaction | T1 sex-specific (11.2–20.3 kg/m 2 ) | T2 sex-specific (20.2–22.5 kg/m 2 ) | T3 sex-specific (22.4–46.9 kg/m 2 ) | P for interaction | ||||||||||||||
| N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | ||||
| rs10997870 | TT | 222/2883 | 1 | (ref.) | 168/2946 | 0.67 | (0.49,0.91) | 201/2616 | 0.88 | (0.63,1.22) | 144/3006 | 1 | (ref.) | 162/3265 | 1.07 | (0.76,1.49) | 146/2892 | 1.16 | (0.80,1.69) | ||
| TG/GG | 264/4459 | 1 | (ref.) | 282/4142 | 1.18 | (0.91,1.54) | 280/4141 | 1.09 | (0.84,1.43) | 0.03b | 224/4993 | 1 | (ref.) | 224/4867 | 1.05 | (0.81,1.37) | 212/4723 | 1.05 | (0.79,1.39) | 0.98 | |
| rs12778366 | TT | 363/5144 | 1 | (ref.) | 343/5209 | 0.93 | (0.74,1.18) | 358/4952 | 0.99 | (0.78,1.26) | 274/5528 | 1 | (ref.) | 287/5986 | 1.00 | (0.79,1.27) | 270/5474 | 1.04 | (0.79,1.35) | ||
| TC/CC | 123/2197 | 1 | (ref.) | 107/1880 | 1.00 | (0.67,1.48) | 123/1805 | 1.07 | (0.71,1.60) | 0.82 | 94/2472 | 1 | (ref.) | 99/2146 | 1.32 | (0.87,2.00) | 88/2127 | 1.21 | (0.79,1.84) | 0.72 | |
| Non-occupational physical activity | Non-occupational physical activity | ||||||||||||||||||||
| ≤30 min/day | >30–60 min/day | >60 min/day | P for interaction | ≤30 min/day | >30–60 min/day | >60 min/day | P for interaction | ||||||||||||||
| N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | ||||
| rs10997870 | TT | 123/1540 | 1 | (ref.) | 220/3442 | 0.80 | (0.57,1.13) | 367/5584 | 0.81 | (0.58,1.12) | 122/1752 | 1 | (ref.) | 156/3272 | 0.69 | (0.48,1.00) | 205/4957 | 0.61 | (0.43,0.86) | ||
| TG/GG | 151/2559 | 1 | (ref.) | 295/5145 | 0.92 | (0.69,1.23) | 562/7945 | 1.15 | (0.88,1.50) | 0.15 | 191/3843 | 1 | (ref.) | 233/5298 | 0.90 | (0.69,1.18) | 310/6943 | 0.90 | (0.70,1.16) | 0.17 | |
| rs12778366 | TT | 214/2873 | 1 | (ref.) | 390/6509 | 0.77 | (0.60,1.00) | 681/9816 | 0.90 | (0.71,1.14) | 235/3761 | 1 | (ref.) | 283/6103 | 0.76 | (0.59,0.98) | 387/8707 | 0.72 | (0.57,0.91) | ||
| TC/CC | 60/1226 | 1 | (ref.) | 125/2078 | 1.20 | (0.76,1.88) | 248/3712 | 1.33 | (0.88,2.00) | 0.18 | 78/1834 | 1 | (ref.) | 106/2453 | 1.04 | (0.70,1.57) | 128/3193 | 0.89 | (0.60,1.32) | 0.42 | |
| Height | Height | ||||||||||||||||||||
| T1 sex-specific (147–173 cm) | T2 sex-specific (174–179 cm) | T3 sex-specific (180–202 cm) | P for interaction | T1 sex-specific (140–163 cm) | T2 sex-specific (164–168 cm) | T3 sex-specific (169–200 cm) | P for interaction | ||||||||||||||
| N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | ||||
| rs10997870 | TT | 238/3843 | 1 | (ref.) | 240/3411 | 1.15 | (0.87,1.51) | 232/3313 | 1.20 | (0.91,1.59) | 167/3808 | 1 | (ref.) | 162/3354 | 1.24 | (0.90,1.70) | 154/2818 | 1.34 | (0.96,1.87) | ||
| TG/GG | 297/5261 | 1 | (ref.) | 336/5055 | 1.25 | (0.99,1.58) | 375/5332 | 1.37 | (1.08,1.73) | 0.76 | 230/6212 | 1 | (ref.) | 275/5468 | 1.37 | (1.07,1.74) | 229/4404 | 1.44 | (1.11,1.87) | 0.76 | |
| rs12778366 | TT | 408/6730 | 1 | (ref.) | 438/6281 | 1.17 | (0.95,1.44) | 439/6187 | 1.23 | (1.00,1.51) | 296/7193 | 1 | (ref.) | 320/6286 | 1.30 | (1.04,1.63) | 289/5092 | 1.46 | (1.15,1.86) | ||
| TC/CC | 127/2374 | 1 | (ref.) | 138/2185 | 1.30 | (0.91,1.87) | 168/2458 | 1.46 | (1.01,2.09) | 0.91 | 101/2827 | 1 | (ref.) | 117/2523 | 1.32 | (0.91,1.92) | 94/2130 | 1.20 | (0.81,1.79) | 0.76 | |
| Residence Hunger Winter | Residence Hunger Winter | ||||||||||||||||||||
| Non-Western area | Western rural area | Western city | P for interaction | Non-Western area | Western rural area | Western city | P for interaction | ||||||||||||||
| N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | N cases/PT at risk | HR a | (95% CI) | ||||
| rs10997870 | TT | 393/4973 | 1 | (ref.) | 75/1402 | 0.75 | (0.52,1.07) | 126/2177 | 0.74 | (0.54,1.01) | 247/5204 | 1 | (ref.) | 80/1372 | 1.35 | (0.92,1.98) | 130/2914 | 0.96 | (0.70,1.31) | ||
| TG/GG | 505/7945 | 1 | (ref.) | 141/1901 | 1.27 | (0.94,1.70) | 201/3242 | 0.96 | (0.75,1.23) | 0.06 | 373/8610 | 1 | (ref.) | 113/2315 | 1.17 | (0.87,1.58) | 206/4172 | 1.17 | (0.92,1.49) | 0.36 | |
| rs12778366 | TT | 697/9391 | 1 | (ref.) | 142/2267 | 0.92 | (0.70,1.21) | 225/3968 | 0.76 | (0.60,0.95) | 466/9984 | 1 | (ref.) | 144/2662 | 1.20 | (0.92,1.59) | 245/4940 | 1.08 | (0.86,1.35) | ||
| TC/CC | 201/3527 | 1 | (ref.) | 74/1036 | 1.31 | (0.85,2.01) | 102/1451 | 1.18 | (0.81,1.73) | 0.08 | 154/3816 | 1 | (ref.) | 49/1025 | 1.24 | (0.78,1.98) | 91/2145 | 1.09 | (0.76,1.55) | 0.97 | |
| Residence World War 2 | Residence World War 2 | ||||||||||||||||||||
| Rural area | Urban area | P for interaction | Rural area | Urban area | P for interaction | ||||||||||||||||
| N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | ||||||||||
| rs10997870 | TT | 252/3885 | 1 | (ref.) | 288/4116 | 1.14 | (0.87,1.49) | 191/3632 | 1 | (ref.) | 181/4124 | 0.82 | (0.61,1.12) | ||||||||
| TG/GG | 389/5734 | 1 | (ref.) | 367/5679 | 0.95 | (0.76,1.18) | 0.48 | 263/5466 | 1 | (ref.) | 294/6157 | 1.00 | (0.78,1.27) | 0.28 | |||||||
| rs12778366 | TT | 472/7058 | 1 | (ref.) | 485/7304 | 0.99 | (0.82,1.21) | 350/6645 | 1 | (ref.) | 345/7228 | 0.91 | (0.73,1.13) | ||||||||
| TC/CC | 169/2560 | 1 | (ref.) | 170/2491 | 1.07 | (0.76,1.51) | 0.83 | 104/2453 | 1 | (ref.) | 130/3052 | 1.02 | (0.71,1.48) | 0.59 | |||||||
| Employment status father Economic Depression | Employment status father Economic Depression | ||||||||||||||||||||
| Employed | Unemployed | P for interaction | Employed | Unemployed | P for interaction | ||||||||||||||||
| N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | N cases/ PT at risk | HR a | (95% CI) | ||||||||||
| rs10997870 | TT | 602/9230 | 1 | (ref.) | 80/927 | 1.35 | (0.93,1.97) | 417/8710 | 1 | (ref.) | 46/994 | 0.96 | (0.61,1.51) | ||||||||
| TG/GG | 873/13333 | 1 | (ref.) | 103/1644 | 0.89 | (0.65,1.22) | 0.09 | 632/13459 | 1 | (ref.) | 70/1662 | 0.88 | (0.62,1.23) | 0.74 | |||||||
| rs12778366 | TT | 1099/16567 | 1 | (ref.) | 137/1842 | 1.07 | (0.81,1.41) | 782/15873 | 1 | (ref.) | 85/1853 | 0.91 | (0.66,1.25) | ||||||||
| TC/CC | 376/5996 | 1 | (ref.) | 46/728 | 1.03 | (0.64,1.66) | 0.69 | 267/6282 | 1 | (ref.) | 31/803 | 0.93 | (0.56,1.54) | 0.94 | |||||||
Abbreviations: BMI, body mass index; CI, confidence interval; HR, hazard ratio; N, number of; PT, person-time; ref., reference; T1–3, tertile 1–3.
aAdjusted for age (years), first-degree family history of colorectal cancer (yes/no), smoking status (never, ex, current), alcohol intake (0, 0.1–29, ≥30 g/d), meat intake (g/d), processed meat intake (g/d), and total energy intake (kcal/d); all models except models for physical activity were additionally adjusted for physical activity (≤30, >30–60, >60 min/day); all models, except models for BMI and physical activity, were additionally adjusted for baseline BMI (kg/m2).
bRemained significant after comparison with the p-value adjusted for the Benjamini and Hochberg false discovery rate, setting the false discovery threshold at 0.20.