TABLE 4:
Subgroup analyses of vitamin D and calcium supplementation and risk of serrated polyps during treatment phase (N=2058)
| Any Serrated Polyp | Hyperplastic Polyp | Sessile Serrated Adenoma/Polyp | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SUBGROUP | Events/N1 | Vitamin D aRR (95% CI) | Events/N2 | Calcium aRR (95% CI) | Events/N1 | Vitamin D aRR (95% CI) | Events/N2 | Calcium aRR (95% CI) | Events/N1 | Vitamin D aRR (95% CI) | Events/N2 | Calcium aRR (95% CI) |
| Baseline serum vitamin D | ||||||||||||
| ≤ 23.16 ng/ml | 145/523: 130/494 | 0.94 (0.76–1.15) | 91/372: 118/380 | 1.18 (0.92–1.50) | 132/521: 111/494 |
0.88 (0.70–1.11) | 81/372: 105/379 | 1.22 (0.94–1.57) | 17/511: 28/484 | 1.61 (0.87–2.98) | 15/365: 16/366 | 0.92 (0.45–1.86) |
| > 23.16 ng/ml | 133/508: 157/533 | 1.09 (0.88–1.33) | 112/391: 113/384 | 1.02 (0.81–1.29) | 117/508: 134/533 | 1.04 (0.83–1.30) | 95/391: 99/384 |
1.07 (0.83–1.38) | 25/497: 30/522 | 1.09 (0.66–1.81) | 21/380: 23/374 | 1.07 (0.61–1.89) |
| p | 0.30 | 0.42 | 0.29 | 0.49 | 0.35 | 0.77 | ||||||
| Baseline dietary calcium | ||||||||||||
| ≤ 597 mg/day | 133/466: 130/484 | 0.92 (0.74–1.14) | 93/350: 101/326 | 1.14 (0.88–1.47) | 124/464: 106/484 | 0.79 (0.63–1.01) | 81/350: 90/325 | 1.18 (0.90–1.55) | 17/454: 29/472 | 1.67 (0.92–3.06) | 93/350: 101/326 | 1.07 (0.53–2.15) |
| > 597 mg/day | 131/500: 133/463 | 1.05 (0.85–1.30) | 101/355: 108/383 | 1.01 (0.80–1.28) | 111/500: 117/463 | 1.09 (0.86–1.38) | 87/355: 93/383 | 1.02 (0.78–1.32) | 25/489: 26/457 | 0.99 (0.57–1.74) | 101/355: 108/383 | 1.08 (0.56–2.05) |
| p | 0.39 | 0.52 | 0.07 | 0.46 | 0.21 | 0.79 | ||||||
| Baseline vitamin D/calcium supplementation3 | ||||||||||||
| <400 IU or mg/day | 147/523: 141/514 | 0.97 (0.80–1.19) | 192/721: 211/719 | 1.09 (0.92–1.29) | 132/522: 120/514 | 0.91 (0.73–1.14) | 167/721: 185/718 | 1.11 (0.92–1.34) | 20/508: 30/500 | 1.37 (0.78–2.39) | 32/704: 38/697 | 1.11 (0.70–1.76) |
| ≥400 IU or mg/day | 130/502: 144/511 | 1.04 (0.84–1.29) | 11/40: 19/41 | 1.60 (0.84–3.06) | 116/501: 123/571 | 0.99 (0.78–1.24) | 9/40: 18/41 | 1.88 (0.92–3.86) | 22/494: 28/504 | 1.17 (0.67–2.04) | 4/39: 1/36 | 0.09 (0.01–1.54) |
| p | 0.65 | 0.30 | 0.60 | 0.21 | 0.63 | 0.25 | ||||||
| Sex | ||||||||||||
| Male | 182/649: 178/656 | 0.96 (0.80–1.15) | 171/656: 189/649 | 1.11 (0.92–1.33) | 163/649: 154/656 | 0.92 (0.76–1.12) | 150/656: 167/649 | 1.12 (0.92–1.37) | 28/635: 36/640 | 1.21 (0.74–1.98) | 28/642: 36/633 | 1.20 (0.74–1.95) |
| Female | 96/382: 109/371 | 1.10 (0.86–1.40) | 32/107: 42/115 | 1.19 (0.81–1.76) | 86/380: 91/371 | 1.02 (0.78–1.33) | 26/107: 37/114 | 1.28 (0.82–1.98) | 14/373: 22/366 | 1.39 (0.71–2.74) | 8/103: 3/107 | 0.42 (0.10–1.83) |
| p | 0.33 | 0.73 | 0.55 | 0.56 | 0.60 | 0.10 | ||||||
| Race | ||||||||||||
| White | 226/873: 255/874 | 1.08 (0.92–1.26) | 181/669: 199/646 | 1.12 (0.94–1.34) | 197/871: 214/874 | 1.03 (0.87–1.23) | 154/669: 172/645 | 1.15 (0.95–1.40) | 40/855: 55/857 | 1.29 (0.87–1.92) | 36/653: 37/628 | 1.00 (0.64–1.56) |
| Black | 26/79: 17/81 | 0.63 (0.36–1.10) | 10/42: 19/69 | 1.09 (0.54–2.21) | 26/79: 17/81 | 0.63 (0.36–1.10) | 10/42: 19/69 | 1.09 (0.54–2.21) | 1/75: 2/79 | 1.93 (0.26–14.47) | 0/41: 2/65 | NE |
| Other/Multiple | 13/36: 9/32 | 0.76 (0.34–1.70) | 10/26: 6/24 | 0.62 (0.21–1.83) | 13/36: 8/32 | 0.65 (0.28–1.51) | 10/26: 6/24 | 0.62 (0.21–1.83) | 0/35: 1/31 | NE | 0/25: 0/23 | NE |
| p | 0.38 | 0.69 | 0.39 | 0.66 | 0.48 | NE | ||||||
| Body mass index | ||||||||||||
| <25 kg/m2 | 53/285: 67/253 | 1.08 (0.78–1.49) | 35/147: 48/157 | 1.35 (0.91–2.00) | 43/224: 56/253 | 1.06 (0.73–1.53) | 28/147: 41/157 | 1.54 (0.98–2.41) | 13/221: 15/248 | 1.06 (0.52–2.15) | 10/141: 8/154 | 0.64 (0.27–1.50) |
| 25–29.9 kg/m2 | 111/423: 110/414 | 1.03 (0.82–1.31) | 83/337: 94/329 | 1.16 (0.89–1.51) | 101/423: 90/414 | 0.96 (0.74–1.24) | 73/337: 80/329 | 1.13 (0.85–1.50) | 19/416: 20/409 | 1.04 (0.55–1.97) | 9/335: 22/319 | 2.46 (1.13–5.34) |
| ≥ 30 kg/m2 | 114/382: 110/360 | 0.98 (0.78–1.23) | 85/278: 89/278 | 1.01 (0.78–1.32) | 105/381: 99/360 | 0.94 (0.74–1.20) | 75/278: 83/277 | 1.07 (0.81–1.41) | 10/370: 23/349 | 2.25 (1.08–4.69) | 17/268: 9/267 | 0.43 (0.19–0.98) |
| p | 0.71 | 0.16 | 0.65 | 0.21 | 0.12 | 0.16 | ||||||
| Smoking status | ||||||||||||
| Never/Former | 242/942: 246/922 | 1.00 (0.85–1.17) | 183/696: 194/690 | 1.04 (0.87–1.24) | 215/940: 210/922 | 0.96 (0.81–1.14) | 158/696: 171/689 | 1.07 (0.88–1.30) | 36/922: 49/907 | 1.34 (0.88–2.06) | 34/682: 33/671 | 0.90 (0.56–1.45) |
| Current | 36/89: 41/105 | 1.01 (0.68–1.50) | 20/67: 37/74 | 2.16 (1.32–3.51) | 34/89: 35/105 | 0.89 (0.59–1.35) | 18/67: 33/74 | 1.93 (1.16–3.20) | 6/86: 9/99 | 1.24 (0.44–3.48) | 2/63: 6/69 | 4.60 (1.11–19.05) |
| p | 0.93 | 0.02 | 0.68 | 0.06 | 0.85 | 0.15 | ||||||
| Alcohol use | ||||||||||||
| 0 drinks/day | 87/327: 72/300 | 0.85 (0.65–1.13) | 51/205: 59/205 | 1.17 (0.85–1.63) | 74/325: 62/300 | 0.89 (0.65–1.21) | 43/205: 50/204 | 1.26 (0.87–1.82) | 17/318: 14/291 | 0.98 (0.49–2.00) | 12/199: 11/194 | 0.95 (0.42–2.19) |
| 0.1–1 drinks/day | 97/393: 111/380 | 1.08 (0.85–1.37) | 78/270: 80/284 | 0.95 (0.72–1.25) | 85/393: 89/380 | 1.00 (0.77–1.31) | 66/270: 66/284 | 0.91 (0.67–1.23) | 16/388: 24/377 | 1.32 (0.70–2.46) | 11/265: 16/282 | 1.24 (0.57–2.67) |
| > 1 drink/day | 80/246: 80/267 |
0.91 (0.69–1.20) | 65/230: 70/220 | 1.12 (0.82–1.51) | 76/246: 72/267 | 0.85 (0.63–1.14) | 59/230: 67/220 | 1.24 (0.90–1.71) | 9/237: 17/261 | 1.68 (0.77–3.68) | 11/223: 11/212 | 0.94 (0.42–2.11) |
| p | 0.79 | 0.58 | 0.61 | 0.46 | 0.34 | 0.90 | ||||||
| Baseline NSAID/ASA use | ||||||||||||
| < 4 days/week | 145/575: 160/587 | 1.08 (0.88–1.31) | 95/402: 124/419 | 1.21 (0.95–1.54) | 134/574: 135/587 | 0.96 (0.77–1.19) | 84/402: 111/418 | 1.25 (0.97–1.62) | 24/562: 34/575 | 1.33 (0.80–2.23) | 19/391: 20/406 | 0.92 (0.49–1.70) |
| ≥ 4 days/week | 133/456: 127/440 | 0.93 (0.75–1.15) | 108/361: 107/345 | 1.03 (0.82–1.30) | 115/455: 110/440 | 0.94 (0.75–1.19) | 92/361: 93/345 | 1.05 (0.81–1.36) | 18/446: 24/431 | 1.30 (0.70–2.43) | 17/354: 19/334 | 1.11 (0.58–2.13) |
| p | 0.34 | 0.33 | 0.88 | 0.32 | 0.94 | 0.71 | ||||||
| Surveillance interval | ||||||||||||
| 3 year | 154/526: 147/531 | 0.92 (0.76–1.12) | 106/390: 119/402 | 1.09 (0.87–1.37) | 139/525: 130/531 | 0.91 (0.74–1.13) | 94/390: 106/401 | 1.11 (0.86–1.43) | 23/517: 23/519 | 0.89 (0.51–1.56) | 19/381: 16/391 | 0.86 (0.45–1.66) |
| 5 year | 124/505: 140/496 | 1.13 (0.91–1.39) | 97/373: 112/362 | 1.17 (0.92–1.48) | 110/504: 115/496 | 1.03 (0.81–1.31) | 82/373: 98/362 | 1.22 (0.93–1.58) | 19/491: 35/487 | 1.82 (1.05–3.15) | 19/364: 23/349 | 1.17 (0.65–2.11) |
| p | 0.20 | 0.64 | 0.48 | 0.60 | 0.09 | 0.44 | ||||||
All models adjusted for age, sex, center, treatment arm (where appropriate), and number of baseline serrated polyps (0, 1, 2+). Where necessary due to sparse data, clinical center was grouped by prevalence of serrated lesions at baseline into low (Georgia, Iowa, Minnesota, and California), medium (New Hampshire, Colorado, South Carolina, and Puerto Rico), high (Texas, Ohio, and North Carolina). Analyses of no vitamin D vs. vitamin D include all randomized participants; analyses of no calcium vs. calcium are restricted to full factorial participants. p values are for interaction. NSAID: nonsteroidal anti-inflammatory drug; ASA: aspirin; NE: no estimate.
1
# events/N in the group receiving Vitamin D: # events/N in the group not receiving Vitamin D
2
# events/N in the group receiving Calcium: # events/N in the group not receiving Calcium
3
Effects of Vitamin D supplementation are presented for baseline vitamin D use and effects of calcium supplementation are presented for baseline calcium use