Table 2.

pIKKα/β, TLR4, and TLR5 expression in the full length of crypts and stroma in the normal-appearing rectal mucosa of the adjunct biomarker study participants (n = 105) during the triala

Baseline1-Year follow-upRelative Rx effectc
GeometricbGeometricb
Treatment groupNMean (95% CI)PhMean (95% CI)PiMean (95% CI)PjAbsoluted Rx effect
pIKKα/β (OD), crypts
 No calcium29892.2 (631.4–1,260.8)905.1 (653.5–1,253.8)
 Calciume34780.1 (566.9–1,073.6)0.571,054.9 (780.8–1,425.2)0.491.33 (0.88–2.03)0.18261.88
 No vitamin D51781.5 (621.7–982.4)911.4 (724.7–1,146.2)
 Vitamin Df54753.5 (603.3–941.1)0.82872.4 (698.1–1,090.1)0.790.99 (0.73–1.36)0.96–11.05
 Calcium only39753.6 (605.0–938.7)872.7 (676.7–1,125.5)
 Vit. D + calciumg37694.0 (553.9–869.5)0.60899.8 (693.0–1,168.4)0.871.12 (0.78–1.60)0.5386.80
TLR4 (OD), crypts
 No calcium29617.7 (475.6–802.2)618.7 (476.4–803.4)
 Calcium34576.2 (447.7–741.7)0.68628.2 (488.1–808.7)0.931.09 (0.71–1.67)0.6951.01
 No vitamin D51625.4 (501.6–779.7)611.6 (490.5–762.4)
 Vitamin D54545.1 (442.3–671.8)0.34486.9 (395.1–600.1)0.120.91 (0.65–1.28)0.60–44.34
 Calcium only39643.4 (482.3–858.2)614.2 (460.5–819.3)
 Vit. D + calcium37534.3 (402.8–708.8)0.30460.7 (347.3–611.2)0.110.90 (0.60–1.36)0.62–44.49
TLR4 (OD), stroma
 No calcium29113.4 (80.9–159.0)97.5 (69.9–136.0)
 Calcium34119.7 (87.6–163.6)0.8198.4 (72.4–133.9)0.970.96 (0.55–1.65)0.87–5.37
 No vitamin D51111.3 (86.2–142.6)92.1 (68.6–123.6)
 Vitamin D54103.0 (80.4–132.0)0.6771.8 (53.9–95.6)0.230.84 (0.53–1.34)0.47–12.00
 Calcium only39115.9 (86.9–154.6)91.9 (64.7–130.6)
 Vit. D + calcium3793.8 (69.8–126.1)0.3161.3 (42.7–88.0)0.110.82 (0.47–1.46)0.50–8.44
TLR5 (OD), crypts
 No calcium29403.6 (258.6–629.9)288.0 (170.6–486.0)
 Calcium34495.6 (328.5–747.6)0.50331.0 (204.1–536.7)0.700.94 (0.47–1.88)0.85–48.94
 No vitamin D51410.6 (293.9–573.9)281.7 (194.0–409.0)
 Vitamin D54294.0 (212.4–407.0)0.16217.0 (151.0–311.8)0.321.08 (0.62–1.86)0.7951.99
 Calcium only39379.1 (263.3–545.7)277.1 (177.6–432.4)
 Vit. D + calcium37278.1 (191.3–404.2)0.24192.5 (121.9–303.9)0.260.95 (0.5–1.80)0.8716.31
TLR5 (OD), stroma
 No calcium29201.2 (130.6–310.0)148.7 (83.1–266.1)
 Calcium34211.0 (141.6–314.5)0.87113.7 (66.4–194.6)0.500.73 (0.39–1.35)0.31–44.76
 No vitamin D51179.1 (127.8–251.0)99.1 (66.0–148.9)
 Vitamin D54122.4 (88.2–169.9)0.1189.6 (60.4–133.1)0.731.32 (0.82–2.12)0.2447.21
 Calcium only39153.7 (105.3–224.3)84.0 (53.7–131.4)
 Vit. D + calcium37110.2 (74.7–162.4)0.2274.2 (46.9–117.4)0.701.23 (0.70–2.17)0.4733.73
  • Abbreviations: OD, optical density; Rx, treatment; Vit. D, vitamin D.

  • aThe effect of treatment agent on biomarker level was modeled using mixed linear models, implemented using PROC MIXED in SAS 9.4.

  • bData natural log-transformed; reported values are optical density geometric mean (95% CI).

  • cRelative Rx effect (treatment effect on the ratio scale) = [(treatment group follow-up)/(treatment group baseline)]/[(placebo group follow-up)/(placebo group baseline)]. A relative effect of 1.3 would indicate a 30% increase in biomarker expression in the treatment group relative to the control group.

  • dAbsolute Rx effect (treatment effect on the difference scale) = [(treatment group follow-up) - (treatment group baseline] – [(placebo group follow-up) – (placebo group baseline)].

  • eCalcium group comprised patients assigned to either calcium or to calcium + vitamin D (combined) in the 4-arm randomization; patients in the 2-arm randomization were excluded.

  • fVitamin D group comprised patients assigned to vitamin D or to calcium + vitamin D (combined) in the 4-arm randomization, or to vitamin D in the 2-arm randomization.

  • gVitamin D and calcium group comprised patients assigned to calcium + vitamin D (combined) in the 4-arm randomization, or to vitamin D in the 2-arm randomization.

  • hP value for the difference between baseline geometric mean for the treatment group and baseline geometric mean for the control group; from a mixed linear model.

  • iP value for the difference between 1-year follow-up geometric mean for the treatment group and 1-year follow-up geometric mean for the control group; from a mixed linear model.

  • jP value for the relative treatment effect on the ratio scale; from a mixed linear model.