Table 4.

Associations of treatment assignment with recurrent colorectal adenoma risk, according to selected participant characteristics, in the posttreatment observational follow-up phase (N = 1,121)

Any adenomaAdvanced adenomaHigh-risk findinga
Vitamin DbCalciumcVitamin DCalciumVitamin DCalcium
N = 1,108N = 850N = 1,113N = 854N = 1,096N = 838
# events/N (%)RR (95% CI)# events/N (%)RR (95% CI)# events/N (%)RR (95% CI)# events/N (%)RR (95% CI)# events/N (%)RR (95% CI)# events/N (%)RR (95% CI)
Baseline characteristics
SexPint = 0.47Pint = 0.01Pint = 0.95Pint = 0.74Pint = 0.72Pint = 0.73
 Male415/735 (56.5)1.01 (0.89–1.15)415/735 (56.5)0.89 (0.78–1.01)72/738 (9.8)1.33 (0.84–2.10)72/738 (9.8)1.06 (0.68–1.64)157/724 (21.7)1.09 (0.82–1.45)157/724 (21.7)1.03 (0.78–1.36)
 Female154/373 (41.3)1.12 (0.87–1.44)54/115 (47.0)1.46 (0.95–2.25)32/375 (8.5)1.37 (0.75–2.52)13/116 (11.2)1.25 (0.53–2.96)59/372 (15.9)0.98 (0.61–1.57)21/114 (18.4)0.80 (0.37–1.74)
BMIPint = 0.27Pint = 0.94Pint = 0.31Pint = 0.20Pint = 0.21Pint = 0.17
 < 25 kg/m2113/240 (47.1)1.18 (0.89–1.57)81/158 (51.3)0.84 (0.60–1.17)26/241 (10.8)1.64 (0.74–3.63)19/158 (12.0)1.77 (0.66–4.76)39/239 (16.3)1.15 (0.62–2.16)28/157 (17.8)1.25 (0.60–2.61)
 25–29.9 kg/m2245/466 (52.6)1.08 (0.90–1.29)209/381 (54.9)1.03 (0.85–1.25)31/467 (6.6)1.45 (0.70–3.01)27/382 (7.1)1.23 (0.58–2.61)85/460 (18.5)1.22 (0.82–1.81)72/375 (19.2)1.16 (0.75–1.79)
 ≥ 30 kg/m2211/402 (52.5)0.97 (0.80–1.18)179/311 (57.6)0.91 (0.75–1.11)47/405 (11.6)1.10 (0.64–1.91)39/314 (12.4)0.84 (0.46–1.52)92/397 (23.2)0.87 (0.60–1.27)78/306 (25.5)0.83 (0.55–1.24)
Alcohol usePint = 0.39Pint = 0.52Pint = 0.72Pint = 0.55Pint = 0.28Pint = 1.00
 0 drinks/day171/326 (52.5)1.01 (0.81–1.25)129/218 (59.2)0.86 (0.68–1.09)35/325 (10.8)0.97 (0.50–1.88)25/217 (11.5)0.99 (0.44–2.26)60/325 (18.5)0.77 (0.47–1.25)46/217 (21.2)(0.58–1.79)
 0.1–1 drinks/day208/423 (49.2)1.21 (0.99–1.48)175/321 (54.5)1.02 (0.83–1.26)32/425 (7.5)1.96 (0.99–3.91)27/323 (8.4)1.64 (0.77–3.50)76/415 (18.3)1.08 (0.71–1.64)63/313 (20.1)1.22 (0.76–1.95)
 > 1 drink/day154/288 (53.5)0.95 (0.75–1.19)136/253 (53.8)0.97 (0.76–1.23)28/290 (9.7)1.08 (0.53–2.18)26/254 (10.2)0.91 (0.44–1.86)67/286 (23.4)1.26 (0.80–1.98)59/251 (23.5)1.0 (0.63–1.60)
Serum 25-hydroxy- vitamin DdPint = 0.13Pint = 0.38Pint = 0.93Pint = 0.42Pint = 0.86Pint = 0.10
 ≤ 23.16 ng/mL275/533 (51.6)0.96 (0.81–1.13)225/406 (55.4)0.90 (0.75–1.08)51/534 (9.6)1.23 (0.72–2.10)40/406 (9.9)0.93 (0.51–1.70)103/529 (19.5)1.01 (0.71–1.44)82/402 (20.4)0.80 (0.53–1.19)
 > 23.16 ng/mL294/575 (51.1)1.14 (0.96–1.34)244/444 (55.0)1.00 (0.84–1.19)53/579 (9.2)1.31 (0.77–2.22)45/448 (10.0)1.26 (0.72–2.20)113/567 (19.9)1.07 (0.76–1.51)96/436 (22.0)1.23 (0.85–1.77)
End-of-treatment characteristics
Smoking statusPint = 0.35Pint = 0.68Pint = 0.15Pint = 0.83Pint = 0.45Pint = 0.15
 Never/former526/1036 (50.8)1.02 (0.90–1.15)436/799 (54.6)0.95 (0.84–1.08)95/1043 (9.1)1.41 (0.95–2.08)78/805 (9.7)1.05 (0.69–1.60)201/1026 (19.6)1.09 (0.87–1.40)167/789 (21.2)1.06 (0.81–1.39)
 Current43/72 (59.7)1.39 (0.80–2.41)33/51 (64.7)0.86 (0.48–1.53)9/70 (12.9)0.56 (0.09–3.62)7/49 (14.3)0.85 (0.17–4.30)15/70 (21.4)0.70 (0.23–2.11)11/49 (22.5)0.38 (0.10–1.40)
Dietary calciumPint = 0.28Pint = 0.82Pint = 0.40Pint = 0.10Pint = 0.34Pint = 0.80
 < 794 mg/day269/530 (50.8)1.10 (0.93–1.31)190/331 (57.4)0.94 (0.78–1.14)53/531 (10.0)1.08 (0.65–1.80)39/332 (11.8)1.64 (0.89–3.02)96/523 (18.4)0.93 (0.64–1.35)67/324 (20.7)0.98 (0.64–1.52)
 ≥ 794 mg/day298/575 (51.8)0.97 (0.82–1.14)277/516 (53.7)0.96 (0.82–1.14)51/579 (8.8)1.68 (1.00–2.85)46/519 (8.9)0.83 (0.48–1.41)120/570 (21.1)1.22 (0.87–1.70)111/511 (21.7)1.03 (0.74–1.45)
Calcium supplementationPint = 0.37Pint = 0.02N/AN/APint = 0.46N/A
 < 400 mg/day548/1049 (52.2)1.04 (0.94–1.19)457/815 (56.1)0.91 (0.81–1.03)100/1054 (9.5)1.34 (0.91–1.95)84/819 (10.3)1.09 (0.72–1.63)206/1037 (19.9)1.09 (0.85–1.39)175/803 (21.8)1.00 (0.77–1.31)
 ≥ 400 mg/day19/55 (34.6)0.77 (0.33–1.79)10/32 (31.3)2.47 (0.77–7.89)4/55 (7.3)RR not estimablee1/32 (3.1)RR not estimablee10/55 (18.2)0.49 (0.14–1.65)3/32 (9.4)RR not estimablee
Vitamin D supplementationPint = 0.73Pint = 0.83Pint = 0.10Pint = 0.04Pint = 0.93Pint = 0.05
 < 400 IU/day497/950 (52.3)1.05 (0.93–1.19)412/744 (55.4)0.94 (0.82–1.07)91/954 (9.5)1.47 (0.98–2.19)76/747 (10.2)1.27 (0.82–1.95)187/939 (19.9)1.06 (0.82–1.37)157/733 (21.4)1.11 (0.84–1.47)
 ≥ 400 IU/day70/154 (45.5)1.04 (0.72–1.49)55/103 (53.4)0.96 (0.65–1.42)13/155 (8.4)0.60 (0.20–1.83)9/104 (8.7)0.23 (0.05–1.14)29/153 (19.0)1.21 (0.61–2.40)21/102 (20.6)0.48 (0.21–1.13)
NSAID/aspirin usePint = 0.55Pint = 0.12Pint = 0.14Pint = 0.40Pint = 0.03Pint = 0.51
 < 4 days/week266/549 (48.5)1.01 (0.84–1.20)207/386 (53.6)0.85 (0.70–1.03)51/554 (9.2)0.98 (0.58–1.66)43/390 (11.0)0.88 (0.49–1.56)107/543 (19.7)0.81 (0.57–1.14)84/380 (22.1)0.91 (0.62–1.34)
 ≥ 4 days/week300/555 (54.1)1.08 (0.92–1.26)260/461 (56.4)1.04 (0.88–1.22)53/555 (9.6)1.75 (1.03–2.96)42/461 (9.1)1.30 (0.72–2.34)109/549 (19.9)1.42 (1.01–2.00)94/455 (20.7)1.12 (0.78–1.61)
Adenoma at end-of-treatment colonoscopyPint = 0.94Pint = 0.32Pint = 0.11Pint = 0.74Pint = 0.40Pint = 0.44
 No254/580 (43.8)1.03 (0.86–1.25)204/425 (48.0)0.89 (0.73–1.09)37/587 (6.3)1.88 (0.96–3.68)29/431 (6.7)0.98 (0.48–1.98)81/576 (14.1)1.16 (0.77–1.74)69/421 (16.4)1.15 (0.75–1.79)
 Yes303/506 (59.9)1.04 (0.90–1.21)257/408 (63.0)1.01 (0.87–1.18)67/504 (13.3)1.01 (0.63–1.58)56/406 (13.8)1.14 (0.69–1.87)131/498 (26.3)0.95 (0.71–1.28)106/400 (26.5)0.93 (0.67–1.30)
  • NOTE: Interactions were assessed with the use of Wald test and multiplicative interaction terms. The P values shown are for the interaction between the (vitamin D or calcium) treatment effects and the participant characteristics listed.

  • Analyses of no vitamin D vs. vitamin D included all randomized participants; analyses of calcium vs. no calcium and of both agents vs. neither agent were restricted to full factorial participants; analyses of calcium vs. both agents excluded full factorial participants randomized to placebo or vitamin D alone.

  • All models adjusted for age, center, sex (where appropriate), treatment arm, number of baseline adenomas, surveillance interval (where appropriate)

  • aHigh-risk findings include advanced adenomas and/or ≥2 adenomas.

  • bNumber of events is the total number of subjects with the outcome in the subgroup, N is the number of subjects in the subgroup, RR is the relative risk for vitamin D vs. no vitamin D within the subgroup, P is the P value for interaction between the subgroup variable and vitamin D treatment

  • cNumber of events is the total number of subjects with the outcome in the subgroup, N is the number of subjects in the subgroup, RR is the relative risk for calcium vs. no calcium within the subgroup in the full factorial randomization subjects, P is the P value for interaction between the subgroup characteristic and calcium treatment.

  • dSeasonally adjusted serum 25(OH)D concentration.

  • eData are too sparse to allow estimation of adjusted relative risk.