Table 4. Incidence rate ratios (95% confidence intervals) for colon cancer risk associated with high physical activity^a and proportion explained effect after adjustment for individual biomarkers.

Biomarkers	IRR	95% CIc	ß	PEEd	95% CIe
Multivariable modelb	0.75	0.57 to 0.96	-0.29
Adiposity status
BMI, kg/m2	0.76	0.59 to 0.98	-0.28	6	-2 to 22
Waist circumference, cm	0.78	0.60 to 1.02	-0.24	17	4 to 52
Metabolic dysfunction
HbA1c, %	0.75	0.58 to 0.97	-0.27	5	-6 to 24
C-peptide, ng/mL	0.75	0.58 to 0.97	-0.28	1	-4 to 8
Insulin growth factor axis
IGF-1, mg/L	0.75	0.57 to 0.96	-0.27	4	-2 to 14
IGFBP1, ng/mL	0.76	0.58 to 0.98	-0.27	6	-3 to 24
IGFBP2, ng/mL	0.75	0.57 to 0.96	-0.29	2	-11 to 6
IGFBP3, ng/mL	0.75	0.58 to 0.97	-0.29	1	-11 to 20
Adipokine secretion
Adiponectin, μg/mL	0.75	0.58 to 0.96	-0.29	0	-6 to 8
HMW-adiponectin, μg/mL	0.75	0.58 to 0.96	-0.29	0	-2 to 2
Non-HMW-adiponectin, μg/mL	0.75	0.57 to 0.96	-0.29	0	-13 to 18
Leptin, ng/mL	0.75	0.58 to 0.98	-0.28	6	-1 to 20
sOB-R, ng/mL	0.77	0.60 to 1.01	-0.25	15	1 to 50
Lipid metabolism
HDL-cholesterol, mmol/L	0.76	0.58 to 0.98	-0.27	7	-3 to 28
Triglycerides, mmol/L	0.75	0.58 to 0.96	-0.29	0	-9 to 6
Cholesterol, mmol/L	0.75	0.58 to 0.96	-0.29	0	-9 to 6
LDL-cholesterol, mmol/L	0.75	0.58 to 0.96	-0.29	0	-9 to 6
Oxidative stress
ROM, U/mL	0.74	0.57 to 0.96	-0.30	0	-19 to 15
FRAP, μmol/L	0.74	0.57 to 0.96	-0.29	0	-10 to 5
Vitamin D metabolism
25[OH]D, nmol/L	0.81	0.62 to 1.05	-0.20	30	12 to 88
PTH, pg/mL	0.75	0.58 to 0.97	-0.28	4	-1 to 15
Inflammation and immune response
CRP, mg/L	0.75	0.58 to 0.97	-0.28	3	-2 to11
Neopterin, nmol/L	0.68	0.52 to 0.88	-0.38	-30	-91 to -8

^aHigh physical activity is defined as >91 MET-hours per week of total activity using a 75th percentile of the variable distribution in the controls as cut-point.

^bThe multivariable-adjusted model in conditional logistic regression takes into account matching factors: age, sex, study centre, follow-up time since blood collection, time of the day at blood collection and fasting status; in women further matching by menopausal status, phase of menstrual cycle at blood collection and in postmenopausal women hormonal replacement therapy use. The model is further adjusted for education (no school degree or primary school, technical or professional school, secondary school, university degree, or unknown), smoking status (never, past, current, or unknown), alcohol intake (continuous), fruit and vegetable intake (g/day), fish and shellfish intake (g/day), fibre intake (g/day), red and processed meat intake (g/day).

^cThe β-coefficient (regression coefficient) is the natural log of the relative risk estimate.

^dThe proportion explained effect (PEE) denotes percent change in the regression coefficients with adjustment for each additional biomarker compared with the multivariable-adjusted model.

^eThe corresponding 95% confidence interval (CI) of PEE was calculated based on the Fieller’s theorem.

Abbreviations: IRR, incidence rate ratio; CI, confidence interval; PEE, proportion explained effect; BMI, body mass index; CRP, C-reactive protein; HbA_1c, glycated haemoglobin; IGF-1, insulin growth factor; IGFBP, insulin-like growth factor-binding protein; sOB-R, soluble leptin receptor; HDL-C, high density lipoprotein-cholesterol; LDL-cholesterol, low density lipoprotein cholesterol; ROM, reactive oxygen metabolites; FRAP, ferric reducing ability of plasma; PTH, parathyroid hormone; 25[OH]D, 25-hydroxy-vitamin D.