TABLE 4.

ORs (95% CIs) for coffee-associated metabolites and diagnosis of colorectal cancer in a nested study within the PLCO Cancer Screening Trial (n = 251 incident cases and n = 247 controls) by using conditional logistic regression for metabolites with <20% of individuals below the lower limit of detection¹

	OR (95% CI)
	High metabolite levels compared with none/low
Name	Undetectable/low	High	90th compared with 10th percentiles for each continuously measured metabolite	P-linear trend
Theophylline	Reference	0.75 (0.51, 1.09)	0.44 (0.25, 0.79)	0.006*
Cases/controls, n	147/132	104/115	—
Caffeine	Reference	0.81 (0.55, 1.20)	0.56 (0.35, 0.89)	0.015*
Cases/controls, n	133/125	118/122	—
Paraxanthine	Reference	0.93 (0.63, 1.36)	0.58 (0.36, 0.94)	0.027*
Cases/controls, n	133/130	118/117	—
X_05426	Reference	0.83 (0.58, 1.20)	0.66 (0.41, 1.05)	0.080
Cases/controls, n	134/125	117/122	—
X_14374	Reference	0.85 (0.59, 1.22)	0.82 (0.53, 1.26)	0.366
Cases/controls, n	133/123	118/124	—
Theobromine	Reference	0.94 (0.65, 1.34)	0.83 (0.54, 1.28)	0.405
Cases/controls, n	133/126	118/121	—
Catechol sulfate	Reference	0.98 (0.66, 1.43)	0.83 (0.49, 1.39)	0.473
Cases/controls, n	125/125	126/122	—
Quinate	Reference	0.90 (0.61, 1.33)	0.83 (0.48, 1.44)	0.508
Cases/controls, n	150/146	101/101	—
4-Vinylphenol sulfate	Reference	0.92 (0.63, 1.34)	1.09 (0.63, 1.87)	0.759
Cases/controls, n	134/132	117/115	—

¹Conditional logistic regression of case/control status on categorized relative level of metabolite; ln(metabolite) was rank ordered into low compared with high categories by the median (varied by metabolite). All models were adjusted for tobacco smoking status (current, former, and never), age, and BMI (continuous). Cases and controls were incidence-density matched to cases on age (5-y intervals), year of randomization, season of blood draw, sex, and race. Metabolites with the prefix X_ are of unknown identity. ORs compared subjects with levels below the median value (none/low) to those with levels above the median (high). To have an adequately sized reference group, in these models, individuals with metabolite levels below the lower limit of detection are included in the reference category of those below the median value; none refers to relative metabolite levels below the lower limit of detection. Metabolites with statistically significant coffee-metabolite associations are shown (P < 7.61 × 10⁻⁵; Bonferroni-corrected threshold, P = 0.05 divided by the total number of metabolites detected). Metabolites are ordered by P-linear trend. P-linear trend values are from a conditional logistic regression of case/control status on ln(metabolite). *Significant associations. PLCO, Prostate, Lung, Colorectal, and Ovarian.