Table 5.

Multivariable hazard ratios for associations between aspirin and ibuprofen use and the risk of colorectal cancer by mismatch repair gene mutated

MMR gene/NSAID use	n	N	Person-years	HR* (95% CI)	P
MLH1
Never user†	276	600	11 043	1 (Ref)
Aspirin-only user	13	30	609	0.34 (0.13 to 0.86)	.02
Ibuprofen-only user	13	40	603	0.91 (0.32 to 2.55)	.86
Aspirin and/or ibuprofen user	32	81	1499	0.43 (0.21 to 0.87)	.02
MSH2
Never user†	266	751	10 975	1 (Ref)
Aspirin-only user	18	51	887	0.52 (0.19 to 1.45)	.22
Ibuprofen-only user	8	53	344	0.27 (0.08 to 0.85)	.03
Aspirin and/or ibuprofen user	32	122	1505	0.39 (0.20 to 0.74)	.004
MSH6
Never user†	50	148	2330	1 (Ref)
Aspirin-only user	6	21	352	0.23 (0.04 to 1.06)	.06
Ibuprofen-only user	5	24	242	0.16 (0.03 to 0.72)	.02
Aspirin and/or ibuprofen user	12	56	643	0.27 (0.04 to 1.75)	.17
PMS2
Never user†	30	73	1395	1 (Ref)
Aspirin-only user	11	15	657	1.78 (0.56 to 5.67)	.33
Ibuprofen-only user	4	9	184	1.60 (0.33 to 7.59)	.55
Aspirin and/or ibuprofen user	16	27	901	0.70 (0.33 to 1.47)	.35

* Adjusted for sex, country (USA, Australia/ New Zealand, Canada), average lifetime alcohol intake (0, 1, ≥2 drinks per day), year of birth (1914–43, 1944–54, 1955–65, 1966–90), cigarette smoking status (never, former, current), regular physical activity (at least 30 minutes per week for at least three months), and multivitamin intake (<1 month, ≥1 month), where possible. All statistical tests were two-sided. CI = confidence interval; HR = hazard ratio; n = number of colorectal cancer cases; MMR = DNA mismatch repair; N = total number of carriers; NSAID = nonsteroidal anti-inflammatory drugs.

† Never users defined as carriers who reported not having taken either aspirin or ibuprofen or both for at least one month.