Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk

Table 1 Baseline characteristics of colorectal cancer cases and controls

	Cases (n= 50)		Controls (n= 100)		Pvalue1
Age, yr	51.8	± 5.6	52.1	± 5.6	0.8
Gender					1.0
Men	28	56.0%	56	56.0%
Women	22	44.0%	44	44.0%
Intervention group					1.0
Yes	27	54.0%	54	54.0%
No (placebo)	23	46.0%	46	46.0%
BMI, kg/m²					1.0
< 25	24	48.0%	48	48.0%
≥ 25	26	52.0%	52	52.0%
Waist circumference, cm	88.2	± 12.9	82.2	± 12.1	0.01
Height, cm	169.3	± 7.1	167.8	± 8.5	0.3
Smoking status					0.9
Never smoker	23	46.0%	46	46.0%
Former smoker	21	42.0%	40	40.0%
Current smoker	6	12.0%	14	14.0%
Alcohol intake, g/d	24	± 24.4	15.4	± 16.3	0.01
Physical activity					0.4
Low	10	20.0%	26	26.0%
Moderate	18	36.0%	25	25.0%
High	22	44.0%	49	49.0%
Educational level, yr					0.9
< 12	30	60.0%	61	61.0%
≥ 12	20	40.0%	39	39.0%
Family history of colorectal cancer2
No	45	90.0%	84	84.0%	0.3
Yes	5	10.0%	16	16.0%
Plasma levels of biomarkers
Adiponectin, µg/mL	9.0	± 4.7	10.9	± 7.5	0.2
Leptin, ng/mL	8.5	± 5.3	8.6	± 8.7	0.5
sVCAM-1, ng/mL	750.3	± 316.2	677.6	± 215.3	0.2
sICAM-1, ng/mL	249.7	± 80.3	247.8	± 67.3	0.9
sE-selectin, ng/mL	41.1	± 16.9	39.3	± 16.0	0.7
MCP-1, pg/mL	268.2	± 117.4	249	± 78.2	0.3
hs-CRP, mg/L	2.4	± 4.5	2.2	± 4.4	0.3

¹P value for the comparison of cases and controls by Student t test or χ² test, as appropriate. Biomarker variables were log-transformed to improve normality. Values are mean ± SD or n % as appropriate.

²In first degree relatives. BMI: Body mass index; hs-CRP: Highly sensitive C-reactive protein; sICAM-1: Soluble intercellular adhesion molecule-1; sVCAM-1: Soluble vascular cell adhesion molecule-1; sE-selectin: Soluble E-selectin; MCP-1: Monocyte chemoattractant protein-1.

Table 2 Odds ratios and 95% confidence intervals for quartiles of each biomarker level and colorectal cancer risk from multivariate conditional logistic regression models¹

	For a change in 1SD	Quartile1	Quartile2	Quartile3	Quartile4
Adiponectin
OR	0.45	1 (ref)	0.83	0.42	0.11
95% CI	0.22-0.91		0.12-5.65	0.06-2.93	0.01-0.93
P for linear trend	0.03				0.03
Leptin
OR	0.55	1 (ref)	0.19	2.22	0.29
95% CI	0.21-1.40		0.02-1.9	0.25-20.09	0.02-3.65
P for linear trend	0.2				0.6
sVCAM-1
OR	1.69	1 (ref)	6.89	11.59	19.11
95% CI	0.96-2.98		0.72-66.4	0.64-209.81	1.4-261.27
P for linear trend	0.07				0.02
sICAM-1
OR	0.74	1 (ref)	0.38	0.07	0.13
95% CI	0.40-1.40		0.04-3.23	0.01-0.76	0.01-1.93
P for linear trend	0.4				0.08
sE-selectin
OR	0.95	1 (ref)	1.23	0.9	1.59
95% CI	0.49-1.81		0.13-11.49	0.1-8.14	0.16-15.62
P for linear trend	0.9				0.9
MCP-1
OR	1.35	1 (ref)	1.67	1.02	2.02
95% CI	0.73-2.49		0.27-10.24	0.17-6.24	0.26-15.97
P for linear trend	0.3				0.4
hs-CRP
OR	0.8	1 (ref)	0.73	2.22	1.53
95% CI	0.52-1.24		0.06-9.38	0.25-19.9	0.13-17.84
P for linear trend	0.3				0.6

¹Adjusted for age, sex, body mass index, intervention group, alcohol intake, physical activity, smoking status, family history of colorectal cancer, waist circumference, height and educational level. n = 50 colorectal cancer cases and 100 controls. Cut-offs for sex-specific quartiles were: hs-CRP: 0.6, 1.2, 2.3 in men and 0.5, 0.9, 2.1 in women; sICAM-1: 198.7, 242.0, 287.4 in men and 193.0, 232.5, 286.0 in women; sVCAM-1: 539.0, 653.5, 798.6 in men and 523.0, 651.5, 875.7 in women; sE-selectin: 29.8, 42.5, 51.7 in men and 26.0, 36.3, 44.6 in women; MCP-1: 216.7, 263.5, 316.5 in men and 171.0, 212.0, 238.0 in women; Leptin: 3.1, 5.0, 8.2 in men and 5.4, 9.6, 15.4 in women; Adiponectin: 4.2, 6.6, 10.0 in men and 9.5, 13.9, 16.0 in women. OR: Odds ratio; CI: Confidence interval; hs-CRP: Highly sensitive C-reactive protein; sICAM-1: Soluble intercellular adhesion molecule-1; sVCAM-1: Soluble vascular cell adhesion molecule-1; sE-selectin: Soluble E-selectin; MCP-1: Monocyte chemoattractant protein-1; ref: Reference category.

Table 3 Predictive potential of adiponectin and soluble vascular cell adhesion molecule-1 regarding colorectal cancer risk: Relative integrated discrimination improvement and improvement of area under the curve

	AUC	Pvalue for AUCimprovement	RIDI (%)	95% CI
Multivariate model1	0.89
+ Adiponectin	0.98	0.009	12.2	10.9-13.6
+ sVCAM-1	0.92	0.09	9.9	8.7-11.0
+ Adiponectin + sVCAM-1	0.98	0.01	26.5	24.4-28.7

¹Multivariate model was adjusted for age, sex, BMI, intervention group, alcohol intake, physical activity, smoking status, family history of colorectal cancer, waist circumference, height and educational level. Models including adiponectin and/or sVCAM-1 were compared to the multivariate model. n = 50 colorectal cancer cases and 100 controls. BMI: Body mass index; RIDI: Relative integrated discrimination improvement; AUC: Area under the receiver operating curve; sVCAM-1: Soluble vascular cell adhesion molecule-1; CI: Confidence interval.