Table 4.
Association between the combination of change in serum cytokine concentrations from baseline and interleukin polyporphisms and colorectal adenoma recurrence among intervention group participants of the Polyp Prevention Trial (n = 808)
| Cytokine Changea (in pg/mL) | Interleukin Polymorphism | Adenoma Recurrence (T4)* |
||||||
|---|---|---|---|---|---|---|---|---|
| No | Any | High Risk | Advanced | |||||
| n (%) | n (%) | OR (95% CI)* | n (%) | OR (95% CI)* | n (%) | OR (95% CI)* | ||
| IL-1β | IL-1β -511 | |||||||
| High > 0.01 | TT + CT | 151 (65.7) | 79 (34.3) | 1.00 | 23 (10.0) | 1.00 | 13 (5.7) | 1.00 |
| CC | 93 (62.4) | 56 (37.6) | 1.15 (0.74–1.78) | 18 (12.1) | 1.40 (0.70–2.81) | 9 (6.0) | 1.19 (0.47–3.00) | |
| Low ≤ 0.01 | TT + CT | 121 (58.5) | 86 (41.5) | 1.34 (0.90–1.98) | 17 (8.2) | 0.93 (0.47–1.86) | 9 (4.3) | 0.81 (0.33–2.01) |
| CC | 97 (57.1) | 98 (42.9) | 1.41 (0.93–2.14) | 25 (14.7) | 1.70 (0.83–3.25) | 10 (5.9) | 1.28 (0.52–3.18) | |
| Interaction | P-value | 0.78 | 0.60 | 0.68 | ||||
| IL-6 | IL-6 -174 | |||||||
| High > 0.04 | CC + CG | 141 (60.0) | 94 (40.0) | 1.00 | 29 (12.3) | 1.00 | 16 (6.8) | 1.00 |
| GG | 77 (58.3) | 55 (41.7) | 1.01 (0.64–1.58) | 19 (14.4) | 0.98 (0.49–1.94) | 11 (8.3) | 0.90 (0.37–2.18) | |
| Low ≤ 0.04 | CC + CG | 131 (58.7) | 92 (41.3) | 1.04 (0.71–1.52) | 25 (11.2) | 0.82 (0.45–1.50) | 14 (6.3) | 0.83 (0.38–1.82) |
| GG | 104 (68.4) | 48 (31.6) | 0.70 (0.45–1.09) | 11 (7.2) | 0.47 (0.21–1.02) | 2 (1.3) | 0.14 (0.03–0.65) | |
| Interaction | P-value | 0.20 | 0.30 | 0.06 | ||||
| IL-8 | IL-8 -251 | |||||||
| High > −0.01 | AA + AT | 171 (61.1) | 109 (38.9) | 1.00 | 23 (8.2) | 1.00 | 15 (5.4) | 1.00 |
| TT | 68 (70.1) | 29 (29.9) | 0.69 (0.41–1.14) | 6 (6.2) | 0.74 (0.28–1.95) | 3 (3.1) | 0.55 (0.15–2.01) | |
| Low ≤ −0.01 | AA + AT | 169 (61.0) | 108 (39.0) | 1.00 (0.70–1.52) | 37 (13.4) | 1.65 (0.92–2.94) | 18 (6.5) | 1.19 (0.57–2.49) |
| TT | 50 (55.6) | 40 (44.4) | 1.17 (0.72–1.93) | 10 (11.1) | 1.32 (0.57–3.08) | 5 (5.6) | 1.02 (0.34–3.05) | |
| Interaction | P-value | 0.13 | 0.90 | 0.61 | ||||
| IL-10 | IL-10 -592 | |||||||
| High > −0.04 | AA + AC | 102 (61.8) | 63 (38.2) | 1.00 | 12 (7.3) | 1.00 | 7 (4.2) | 1.00 |
| CC | 134 (60.9) | 86 (39.1) | 1.07 (0.70–1.63) | 33 (15.0) | 2.23 (1.07–4.66) | 20 (9.1) | 2.42 (0.94–6.22) | |
| Low ≤ −0.04 | AA + AC | 102 (59.3) | 70 (40.7) | 1.12 (0.72–1.75) | 21 (12.2) | 1.70 (0.77–3.73) | 9 (5.2) | 1.29 (0.45–3.70) |
| CC | 130 (61.3) | 82 (38.7) | 1.08 (0.70–1.66) | 18 (8.5) | 1.24 (0.56–2.78) | 7 (3.3) | 0.87 (0.28–2.65) | |
| Interaction | P-value | 0.72 | 0.03 | 0.07 | ||||
| IL-10 | IL-10 -819 | |||||||
| High > −0.04 | TT + TC | 101 (60.8) | 65 (39.2) | 1.00 | 12 (7.23) | 1.00 | 7 (4.2) | 1.00 |
| CC | 140 (60.9) | 90 (39.1) | 1.00 (0.66–1.53) | 35 (15.2) | 2.18 (1.05–4.51) | 21 (9.1) | 2.32 (0.91–5.90) | |
| Low ≤ −0.04 | TT + TC | 108 (60.3) | 71 (39.7) | 1.01 (0.65–1.57) | 21 (11.7) | 1.54 (0.70–3.36) | 8 (4.5) | 1.01 (0.34–2.97) |
| CC | 127 (59.3) | 87 (40.7) | 1.08 (0.71–1.66) | 19 (8.9) | 1.25 (0.56–2.76) | 8 (3.7) | 0.94 (0.32–2.79) | |
| Interaction | P-value | 0.83 | 0.05 | 0.20 | ||||
| IL-10 | IL-10 -1082 | |||||||
| High > −0.04 | GG + GA | 168 (61.8) | 104 (38.2) | 1.00 | 34 (12.5) | 1.00 | 22 (8.1) | 1.00 |
| AA | 66 (58.9) | 46 (41.1) | 1.16 (0.74–1.84) | 11 (9.8) | 0.88 (0.41–1.87) | 5 (4.5) | 0.62 (0.22–1.75) | |
| Low ≤ −0.04 | GG + GA | 171 (60.2) | 113 (39.8) | 1.09 (0.77–1.54) | 28 (9.9) | 0.79 (0.45–1.38) | 10 (3.5) | 0.44 (0.20–0.98) |
| AA | 66 (60.6) | 43 (39.4) | 1.05 (0.66–1.67) | 12 (11.0) | 0.85 (0.40–1.78) | 6 (5.5) | 0.63 (0.24–1.68) | |
| Interaction | P-value | 0.57 | 0.70 | 0.27 | ||||
| IL-10 | IL-10 Haplotypeb | |||||||
| High > −0.04 | GG/GA-TT/TC-TT/TC | 182 (62.1) | 111 (37.9) | 1.00 | 30 (10.2) | 1.00 | 6 (5.5) | 1.00 |
| AA-CC-CC | 40 (56.3) | 31 (43.7) | 1.30 (0.76–2.22) | 12 (16.9) | 1.91 (0.88–4.16) | 17 (5.8) | 2.24 (0.88–5.71) | |
| Low ≤ −0.04 | GG/GA-TT/TC-TT/TC | 176 (59.1) | 122 (40.9) | 1.13 (0.80–1.58) | 32 (10.7) | 1.02 (0.58–1.78) | 8 (11.3) | 0.93 (0.45–1.93) |
| AA-CC-CC | 45 (62.5) | 27 (37.5) | 1.08 (0.63–1.86) | 7 (9.7) | 1.07 (0.43–2.67) | 0 (0.0) | ||
| Interaction | P-value | 0.43 | 0.33 | |||||
Multivariate OR and 95% CI models were adjusted for age tertiles (<58, 58–66, >66 yrs), sex, average BMI (<25, 25.0–29.9, ≥30 kg/m2), race (Caucasian, non Caucasian), and current smoking status during the first 3 trial years. An increase in IL-10 concentrations was associated with a significantly greater risk of high risk adenoma recurrence in individuals homozygous with IL-10 -592 C and IL-10 -819 C compared with individuals carrying the IL-10 -592 A and IL-10 -819 T allele, respectively. The combination of decreased IL-6 concentrations and IL-6 -174 GG had a significantly lower risk estimate of advanced adenoma recurrence compared to the other 3 combinations. In individuals with IL-10 -592 CC, IL-10 -819 CC, and IL-10 -1082 AA/AG, a decrease in IL-10 concentration had a significantly lower risk estimate of advanced adenoma recurrence than an increase in IL-10 concentration. The interaction between change in IL-10 concentration and IL-10 haplotype on the risk of advanced adenoma recurrence could not be computed because no individual with a decrease in IL-10 and IL-10 AA-CC-CC haplotype had advanced adenoma recurrence.
Change in cytokine values is defined as difference between the geometric mean value of years 1 and 3 and baseline.
Composed of 3 polymorphic sites: -1082 AA/G, -819 CC/T, and -592 CC/A.