Table 3.

Dose of regular aspirin use and risk of colorectal cancer overall and by tumor-infiltrating lymphocytes

	Tablets/wk				Ptrend*	Pheterogenity‡
	0	0.5–1.5	2–5	≥6
Total colorectal cancer
Person-years	625399	1148842	680674	599431
Cases, No.	226	544	293	236
Age-adjusted RR (95% CI)	1 (reference)	1.09 (0.92–1.28)	0.87 (0.73–1.03)	0.78 (0.65–0.94)	<0.001
Multivariable RR (95% CI)†	1 (reference)	1.07 (0.91–1.26)	0.86 (0.72–1.03)	0.76 (0.63–0.92)	<0.001
Tumor-infiltrating lymphocytes
Low
Cases, No.	178	399	215	164
Age-adjusted RR (95% CI)	1 (reference)	1.05 (0.87–1.26)	0.83 (0.68–1.01)	0.70 (0.56–0.87)	<0.001	0.04
Multivariable RR (95% CI)†	1 (reference)	1.03 (0.86–1.25)	0.82 (0.67–1.01)	0.69 (0.55–0.85)	<0.001	0.04
Intermediate
Cases, No.	30	89	47	40
Age-adjusted RR (95% CI)	1 (reference)	1.20 (0.78–1.84)	0.98 (0.61–1.57)	0.94 (0.58–1.52)	0.31
Multivariable RR (95% CI)†	1 (reference)	1.18 (0.77–1.82)	0.97 (0.61–1.55)	0.92 (0.57–1.49)	0.29
High
Cases, No.	18	56	31	32
Age-adjusted RR (95% CI)	1 (reference)	1.30 (0.75–2.25)	1.05 (0.58–1.89)	1.26 (0.70–2.26)	0.83
Multivariable RR (95% CI)†	1 (reference)	1.28 (0.74–2.21)	1.05 (0.58–1.90)	1.24 (0.69–2.23)	0.85

Abbreviations: CI, confidence interval; HPFS, Health Professionals Follow-up Study; NHS, Nurses’ Health Study; RR, relative risk.

^*Tests for trend were conducted using the median value of each category as a continuous variable.

^†Adjusted for the same set of covariates as in Table 2.

^‡We assessed whether the magnitude of the subtype-specific associations had an increasing or decreasing ordinal trend according to levels of TILs, using a trend test with one degree of freedom, and the statistical significance of this test was presented as P_{heterogeneity}.