Table 5

Subgroup analyses of vitamin D and calcium supplementation and risk of serrated polyps during observational phase (n=1108)

SubgroupAny serrated polypHyperplastic polypSessile serrated adenoma/polyp
Events
/N*
Vitamin D aRR (95% CI)Events
/N†
Calcium aRR (95% CI)Events
/N*1
Vitamin D aRR (95% CI)Events
/N†
Calcium aRR (95% CI)Events
/N*
Vitamin D aRR (95% CI)Events
/N†
Calcium aRR (95% CI)
Baseline serum vitamin D
 ≤23.16 ng/mL78/273: 81/2641.12 (0.86 to 1.46)55/202: 69/2071.18 (0.86 to 1.60)66/273: 66/2631.09 (0.80 to 1.47)48/202: 55/2061.06 (0.75 to 1.49)11/267: 17/2621.60 (0.75 to 3.42)4/199: 18/2034.37 (1.20 to 15.86)
 >23.16 ng/mL81/277: 89/2941.01 (0.77 to 1.32)59/216: 67/2211.07 (0.79 to 1.46)66/275: 73/2921.02 (0.74 to 1.39)53/216: 48/2170.86 (0.60 to 1.23)15/269: 19/2881.31 (0.67 to 2.57)9/210: 18/2141.80 (0.81 to 3.97)
 P0.520.770.720.400.660.23
Serum vitamin D at EOT
 ≤23.16 ng/mL109/386: 54/1931.02 (0.77 to 1.36)55/217: 69/2231.13 (0.83 to 1.54)92/385: 46/1931.02 (0.74 to 1.40)49/217: 56/2221.03 (0.73 to 1.45)14/375: 11/1911.62 (0.76 to 3.45)5/212: 14/2172.51 (0.93 to 6.72)
 >23.16 ng/mL48/158: 115/3601.04 (0.78 to 1.40)59/196: 66/2011.11 (0.82 to 1.49)38/157: 93/3571.06 (0.75 to 1.50)52/196: 46/1970.88 (0.62 to 1.26)11/155: 24/3541.08 (0.53 to 2.21)8/192: 21/1962.45 (1.08 to 5.53)
 p0.940.870.810.470.470.96
Baseline dietary calcium
 ≤597 mg/day79/249: 92/2741.07 (0.82 to 1.38)58/201: 67/1901.19 (0.87 to 1.62)69/245: 80/2731.06 (0.80 to 1.41)53/201: 57/1881.11 (0.79 to 1.54)11/241: 15/2691.43 (0.66 to 3.12)4/197: 15/1863.19 (1.00 to 10.18)
 >597 mg/day75/274: 69:2431.02 (0.77 to 1.35)51/190: 64/2071.16 (0.84 to 1.60)58/273: 53/2411.00 (0.71 to 1.41)43/190: 43/2040.95 (0.64 to 1.39)15/265: 17/2411.27 (0.66 to 2.44)9/186: 18/2001.77 (0.77 to 4.08)
 P0.880.950.850.520.940.42
Dietary calcium at EOT
 ≤378.4 mg/day82/262: 87/2701.03 (0.79 to 1.34)41/166: 61/1641.45 (1.03 to 2.04)68/262: 73/2681.05 (0.78 to 1.41)38/166: 47/1621.20 (0.82 to 1.77)11/254: 17/2661.67 (0.78 to 3.61)2/161: 13/1585.90 (1.34 to 25.98)
 >378.4 mg/day77/287: 83/2861.02 (0.78 to 1.33)73/251: 75/2621.03 (0.78 to 1.36)64/285: 66/2850.95 (0.70 to 1.30)63/251: 56/2590.88 (0.64 to 1.21)15/281: 19/2821.19 (0.64 to 2.23)11/247: 23/2571.99 (0.95 to 4.16)
 P0.770.100.930.200.550.21
Baseline vitamin D/calcium supplementation‡
 <400 IU or mg/day76/268: 87/2781.11 (0.85 to 1.46)107/393: 130/4041.14 (0.92 to 1.41)64/267: 75/2781.14 (0.85 to 1.55)95/393: 98/3990.97 (0.76 to 1.25)11/260: 13/2741.16 (0.52 to 2.59)12/384: 35/3932.70 (1.38 to 5.27)
 ≥400 IU or mgs/day83/280: 81/2780.93 (0.71 to 1.22)7/25: 5/221.03 (0.30 to 3.47)68/279: 62/2750.89 (0.65 to 1.21)6/25: 4/221.08 (0.27 to 4.26)15/274: 23/2741.46 (0.77 to 2.78)1/25: 1/220.81 (0.16 to 4.21)
 p0.340.890.240.920.640.58
Vitamin D/calcium supplementation at EOT‡
 <400 IU or mg/day143/474: 149/4761.04 (0.85 to 1.26)110/397: 131/4141.12 (0.90 to 1.39)117/472: 125/4741.05 (0.84 to 1.32)97/397: 98/4090.96 (0.75 to 1.23)24/462: 28/4681.21 (0.71 to 2.06)13/388: 34/4032.40 (1.26 to 4.56)
 ≥400 IU or mg/day15/74: 21/801.34 (0.73 to 2.45)4/20: 5/122.00 (0.61 to 6.59)14/74: 14/791.00 (0.50 to 2.00)4/20: 5/122.00 (0.61 to 6.59)2/72: 8/804.00 (0.80 to 20.05)0/20: 2/12NE
 P0.470.250.740.170.16NE
Sex
 Male105/362: 109/3671.01 (0.81 to 1.28)105/363: 109/3661.00 (0.80 to 1.26)88/360: 86/3650.95 (0.73 to 1.25)93/363: 81/3620.85 (0.65 to 1.10)16/351: 27/3621.61 (0.88 to 2.93)13/356: 30/3572.24 (1.16 to 4.32)
 Female54/188: 61/1911.13 (0.82 to 1.56)9/55: 27/622.62 (1.39 to 4.95)44/188: 53/1901.21 (0.84 to 1.74)8/55: 22/612.50 (1.22 to 5.13)10/185: 9/1881.00 (0.40 to 2.45)0/53: 6/60NE
 P0.670.0040.360.0040.40NE
Race
 White137/468: 155/4931.05 (0.86 to 1.27)102/377: 124/3751.21 (0.97 to 1.51)112/466: 124/4901.02 (0.81 to 1.28)90/377: 91/3701.02 (0.79 to 1.32)24/456: 36/4861.46 (0.88 to 2.43)13/370: 35/3652.60 (1.36 to 4.98)
 Black13/46: 8/390.86 (0.37 to 2.01)7/22: 8/380.52 (0.21 to 1.28)11/46: 8/390.97 (0.39 to 2.37)6/22: 8/380.59 (0.23 to 1.52)2/45: 0/39NE0/21: 1/38NE
 Other/Multiple3/17: 5/104.01 (0.58 to 27.49)3/7: 2/100.13 (0.01 to 2.47)3/17: 5104.01 (0.58 to 27.49)3/7: 2/100.13 (0.01 to 2.47)0/17: 0/9NE0/6: 0/10NE
 P0.400.280.430.58NENE
Body mass index
 <25 kg/m2 36/110: 41/1320.95 (0.64 to 1.42)23/74: 26/841.10 (0.65 to 1.86)31/110: 33/1310.96 (0.61 to 1.50)21/74: 17/830.73 (0.40 to 1.33)7/108: 7/1300.89 (0.36 to 2.19)3/72: 10/842.81 (0.99 to 8.03)
 25–29.9 kg/m2 57/235: 65/2331.08 (0.79 to 1.49)46/189: 53/1921.10 (0.78 to 1.57)46/234: 50/2311.02 (0.71 to 1.47)39/189: 39/1890.96 (0.65 to 1.44)11/229: 20/2321.81 (0.90 to 3.64)6/186: 18/1882.78 (1.09 to 7.12)
 ≥30 kg/m2 66/205: 64/1931.03 (0.77 to 1.39)45/155: 57/1521.39 (0.99 to 1.95)55/204: 56/1931.10 (0.79 to 1.53)41/155: 47/1511.17 (0.81 to 1.69)8/199: 9/1881.20 (0.46 to 3.15)4/151: 8/1452.04 (0.61 to 6.80)
 P0.760.230.370.160.990.70
Smoking status
 Never/Former143/502: 146/4971.01 (0.83 to 1.24)104/385: 118/3821.14 (0.91 to 1.43)118/500: 117/4940.99 (0.79 to 1.24)92/385: 87/3770.94 (0.73 to 1.23)24/491: 30/4891.30 (0.77 to 2.20)12/377: 32/3732.50 (1.28 to 4.89)
 Current16/48: 24/611.47 (0.82 to 2.64)10/33: 18/461.73 (0.78 to 3.81)14/48: 22/611.42 (0.78 to 2.59)9/33: 16/461.24 (0.59 to 2.61)2/45: 6/612.36 (0.51 to 10.98)1/32: 4/444.33 (0.92 to 20.42)
 P0.430.550.470.400.440.84
Alcohol use
 0 drinks/day46/167: 43/1601.03 (0.71 to 1.48)25/112: 31/1041.52 (0.94 to 2.47)37/166: 37/1591.10 (0.73 to 1.66)22/112: 24/1021.36 (0.80 to 2.33)8/164: 3/1580.43 (0.14 to 1.32)2/109: 5/1027.66 (0.47 to 123.68)
 0.1–1 drinks/day70/222: 65/1991.00 (0.75 to 1.34)50/154: 59/1661.17 (0.85 to 1.62)56/221: 53/1980.99 (0.71 to 1.39)44/154: 43/1640.94 (0.65 to 1.36)15/216: 15/1961.21 (0.59 to 2.48)5/151: 20/1603.47 (1.27 to 9.49)
 >1 drink/day38/131: 53/1581.17 (0.80 to 1.69)34/125: 41/1271.04 (0.69 to 1.56)34/131: 43/1571.02 (0.67 to 1.54)30/125: 33/1260.98 (0.62 to 1.54)3/126: 14/1563.81 (1.09 to 13.25)6/123: 8/1241.30 (0.45 to 3.74)
 P0.600.500.940.630.020.22
Baseline NSAID/ASA use
 <4 days/week88/312: 94/2971.09 (0.85 to 1.40)56/211: 69/2271.15 (0.85 to 1.56)74/312: 77/2951.05 (0.79 to 1.40)51/211: 52/2250.93 (0.66 to 1.31)12/306: 18/2941.60 (0.79 to 3.27)5/206: 17/2253.04 (0.98 to 9.45)
 ≥4 days/week71/238: 76/2611.03 (0.77 to 1.36)58/207: 67/2011.21 (0.89 to 1.63)58/236: 62/2601.00 (0.72 to 1.38)50/207: 51/1981.06 (0.75 to 1.50)14/230: 18/2561.24 (0.63 to 2.43)8/203: 19/1922.36 (1.07 to 5.24)
 P0.610.750.720.580.620.66
NSAID/ASA use at EOT
 <4 days/week76/264: 94/2871.10 (0.85 to 1.43)53/193: 66/1921.23 (0.90 to 1.67)62/264: 76/2851.09 (0.81 to 1.47)47/193: 49/1901.04 (0.73 to 1.49)11/259: 18/2811.60 (0.77 to 3.30)5/186: 16/1902.74 (0.92 to 8.16)
 ≥4 days/week83/284: 76/2691.01 (0.77 to 1.33)61/224: 70/2341.12 (0.82 to 1.51)70/282: 63/2680.99 (0.73 to 1.34)54/224: 54/2310.95 (0.67 to 1.33)15/275: 18/2671.27 (0.64 to 2.50)8/222: 20/2252.47 (1.10 to 5.56)
 P0.500.750.50.780.670.77
  • All models adjusted for age, sex, centre, treatment arm (where appropriate), number of baseline serrated polyps (0, 1, 2+), surveillance interval (where appropriate). Where necessary due to sparse data, clinical centre 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). P values are for interaction. Analyses of no vitamin D versus vitamin D include all randomised participants; analyses of no calcium versus calcium are restricted to full factorial participants.

  • 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.

  • aRR, adjusted risk ratio; ASA, aspirin; EOT, end of treatment; NE, no estimate; NSAID, non-steroidal anti-inflammatory drug.