Article Figures & Data
Figures
- Figure 1.
Summary of the study design, including inclusions and exclusions of study participants.
- Figure 2.
Estimated average intraindividual changes in ln plasma CRP concentrations over time in colorectal cancer cases and matched controls. Linear mixed models were used to estimate marginal effects of time and 95% CIs in 259 cases and 259 matched controls with matched repeated measurements prior to case diagnosis. A, The crude model included participants and matched case–control pairs as random factors, and time between sample collection and case diagnosis, case–control status, and an interaction term between time and case–control status as fixed factors. B, The adjusted model was additionally adjusted for smoking status, recreational physical activity, alcohol intake, diabetes, and BMI, which were included as fixed factors.
Tables
- Table 1.
Baseline characteristics of participants, N (%)a or median (IQR).
All CRP <1 mg/L CRP 1–3 mg/L CRP >3 mg/L Pb Missingc All participants 2,020 793 (39.3) 716 (35.4) 511 (25.3) — 0 CRC status 0.164 Cases 1,010 (50) 385 (48.5) 351 (49.0) 274 (53.6) 0 Controls 1,010 (50) 408 (51.5) 365 (51.0) 237 (46.4) 0 Sex 0.249 Male 1,050 (52.0) 427 (53.8) 372 (52.0) 251 (49.1) 0 Female 970 (48.0) 366 (46.2) 344 (48.0) 260 (50.9) Age at baseline 56.3 (49.9–60.0) 50.3 (49.8–60.0) 59.3 (50.0–60.0) 59.8 (50.0–60.1) <0.001 0 Age at diagnosis of cases 66.4 (60.5–72.6) 65.3 (57.4–71.2) 67.6 (61.7–73.6) 66.8 (61.9–73.0) <0.001 0 Follow-up time of casesd 12.3 (7.5–16.6) 12.3 (7.7–16.5) 12.7 (7.9–17.9) 11.7 (6.4–15.6) 0.035 0 BMI, kg/m2 25.7 (23.5–28.4) 24.4 (22.6–26.4) 26.2 (24.0–28.5) 27.6 (24.9–30.5) <0.001 20 (1.0) Recreational physical activity 0.109 161 (8.0) No physical activity 793 (42.7) 298 (41.2) 277 (41.8) 218 (46.1) Low 472 (25.4) 181 (25.0) 183 (27.6) 108 (22.8) Moderate 504 (27.1) 217 (30.0) 167 (25.2) 120 (25.4) High 90 (4.8) 28 (3.9) 35 (5.3) 27 (5.7) Alcohol intake groups, gram/day 0.589 298 (14.8) Zero 142 (8.2) 49 (7.5) 48 (7.7) 45 (10.1) Below mediane 725 (42.1) 279 (42.7) 263 (42.1) 183 (41.1) Above mediane 855 (49.7) 325 (49.8) 313 (50.2) 217 (48.8) Smoking status 0.001 43 (2.1) Nonsmoker 832 (42.1) 358 (46.0) 300 (43.2) 174 (34.5) Ex-smoker 680 (34.4) 255 (32.7) 237 (34.1) 188 (37.3) Current smoker 465 (23.5) 166 (21.3) 157 (22.6) 142 (28.2) Diabetesf 122 (6.0) 27 (3.4) 47 (6.6) 48 (9.4) <0.001 0 Education level <0.001 43 (2.1) No secondary 1,327 (67.1) 478 (61.2) 498 (71.3) 351 (70.5) Secondary 314 (15.9) 144 (18.4) 99 (14.2) 71 (14.3) Post-secondary 336 (17.0) 159 (20.4) 101 (14.5) 76 (15.3) Abbreviation: CRC, colorectal cancer.
↵aPercent of participants calculated within CRP categories, except for “all participants.”
↵bχ2 tests for differences between CRP groups (% of participants with existing data) for categorical variables, Kruskal–Wallis tests for differences between CRP groups for continuous variables.
↵cN and % of participants in total (N = 2,020). Missing category not included in the statistical comparisons.
↵dFollow-up time from baseline sample collection to CRC diagnosis.
↵eSex-specific median.
↵fObtained from self-reported question (yes/no) or from fasting plasma glucose levels or from 2-hour oral glucose tolerance test levels, according to WHO diagnostic criteria for diabetes mellitus.
- Table 2.
Baseline and follow-up characteristics of participants with repeated measures.
Baseline Repeat Missing (n = 518) (n = 518) Pa Baseline Repeat CRC status — Cases 259 (50) 259 (50) Controls 259 (50) 259 (50) Sex — Male 292 (56.4) 292 (56.4) Female 226 (43.6) 226 (43.6) Follow-up timeb, years 15.6 (12.9–19.0) 5.83 (2.9–9.1) 0 0 Age at sampling, years 50.0 (40.5–50.2) 59.9 (51.0–60.1) <0.001 0 0 CRP mg/L Cases 1.26 (0.52–2.69) 1.90 (0.95–4.06) <0.001 0 0 Controls 1.14 (0.51–2.21) 1.48 (0.78–3.21) <0.001 0 0 BMI, kg/m2 Cases 25.3 (23.4–27.6) 26.4 (24.3–29.1) <0.001 5 (1.9) 0 Controls 24.6 (22.8–27.0) 26.0 (23.4–28.4) <0.001 2 (0.8) 0 Recreational physical activity Cases 0.244 42 (16.2) 27 (10.4) No physical activity 104 (40.2) 108 (41.7) Low 47 (18.1) 52 (20.1) Moderate 61 (23.6) 58 (22.4) High 5 (1.9) 14 (5.4) Controls 0.791 47 (18.1) 31 (12.0) No physical activity 98 (37.8) 106 (40.9) Low 56 (21.6) 52 (20.1) Moderate 49 (18.9) 60 (23.2) High 9 (3.5) 10 (3.9) Alcohol intake groups, grams/day Cases 0.331 44 (17.0) 2 (0.3) Zero 6 (2.8) 10 (3.9) Below medianc 95 (44.2) 97 (37.7) Above medianc 114 (53.0) 150 (58.4) Controls 0.740 41 (15.8) 0 Zero 13 (6.0) 17 (6.6) Below medianc 87 (39.9) 111 (42.9) Above medianc 118 (54.1) 131 (50.6) Smoking status Cases 0.001 6 (2.3) 5 (1.9) Nonsmoker 97 (37.5) 112 (43.2) Ex-smoker 82 (31.7) 103 (39.8) Current smoker 74 (28.6) 39 (15.1) Controls 0.003 6 (2.3) 8 (3.1) Nonsmoker 110 (42.5) 114 (44.0) Ex-smoker 80 (30.9) 103 (39.8) Current smoker 63 (24.3) 34 (13.1) Diabetesd Cases 7 (2.7) 16 (6.2) 0.055 0 0 Controls 2 (0.8) 8 (3.1) 0.055 0 0 Note: N (%) or median (IQR).
Abbreviation: CRC, colorectal cancer.
↵aPaired Wilcoxon signed rank test within the matched case sets for continuous variables, χ2 tests for categorical variables. Cells showing missing data were not included in the statistical comparisons.
↵bFollow-up time from sample collection to CRC diagnosis.
↵cSex-specific median.
↵dObtained from self-reported question (yes/no) and/or from fasting plasma glucose levels and/or from 2-hour oral glucose tolerance test levels, according to WHO diagnostic criteria for diabetes mellitus.
- Table 3.
ORsa and 95% CI of colorectal cancer and colorectal cancer subtypes per 1 unit increase in ln plasma CRP concentrationsb.
CRC subgroup n complete cases/controlsc OR (95% CI) Pheterogeneityd All CRC 835/817 1.03 (0.97–1.09) Sex Male 437/428 1.03 (0.95–1.12) 0.824 Female 398/389 1.02 (0.94–1.11) BRAF/KRAS mutation status BRAF mutated 123/116 1.11 (0.96–1.27) 0.354 KRAS mutated 137/138 1.05 (0.91–1.20) BRAF/KRAS wild-type 320/314 0.99 (0.91–1.08) MSI status MSI 78/70 1.05 (0.87–1.27) 0.833 MSS 504/498 1.03 (0.96–1.09) Tumor location Right colon 258/245 1.02 (0.91–1.13) 0.426 Left colon 247/248 1.09 (0.98–1.22) Rectum 324/318 0.99 (0.90–1.09) Disease stage Stage I–II 395/385 1.01 (0.93–1.10) 0.641 Stage III–IV 390/383 1.04 (0.96–1.14) Lag time <5 years 134/134 1.13 (0.96–1.32) 0.583 5–10 years 202/198 0.98 (0.85–1.12) 10–15 years 251/245 1.01 (0.90–1.13) >15 years 248/240 1.03 (0.93–1.14) Disease stage/lag time Stage III–IV/lag time <5 years 64/61 1.32 (1.01–1.73) 0.288 Stage III–IV/lag time 5–10 years 90/88 0.96 (0.77–1.19) Stage III–IV/lag time 10–15 years 124/122 1.01 (0.87–1.18) Stage III–IV/lag time >15 years 112/112 1.02 (0.88–1.18) BMIe, kg/m2 <25 317/354 0.99 (0.97–1.02) 0.129 25–30 384/343 1.03 (1.00–1.06) >30 134/120 1.02 (0.98–1.06) Abbreviation: CRC, colorectal cancer.
↵aMultivariable ORs adjusted for age, sex, cohort, sample year and fasting status, smoking status, recreational physical activity, alcohol intake, diabetes mellitus, and BMI (model 3). For estimates from model 1 and 2, see Supplementary Table S1.
↵bFrom multiple imputation data.
↵cNumbers (n) per subgroup represent complete cases and controls with complete covariate data, molecular data for the remaining cases were imputed. Complete estimates for all adjusted models for imputed and complete case data are presented in Supplementary Table S1 for comparison.
↵dPheterogeneity between subtypes was tested with Wald test comparing the observed overall log OR and subtype-specific log ORs from the final multivariable model (model 3).
↵eORs from unconditional logistic regression model (model 2) adjusted for all covariates listed above, except BMI.
Supplementary Data
- Supplementary Table 1, Supplementary Table 2, Supplementary Figure 1 - Supplementary Table 1 shows the ORs and 95% CI for increase in CRP concentrations in complete CRC and CRC subtype cases and in multiple imputation analysis. Supplementary Table 2 shows the clinical characteristics in CRC cases by BRAF/KRAS mutation status. Supplementary Figure 1 shows mean CRP concentration (mg/L) for BMI categories (<25, 25-30, and >30).
Volume 29, Issue 7
