Table 4 Duration of acid-suppressive medications use and risk of colorectal cancer.

	No use	Used in 1–2 cycles	Used in ≥3 cycles	P-trend
PPI use
No. of cases	952	159	58
Person-years	1,493,933	288,870	116,229
Age-adjusted HR (95% CI)	Ref.	0.80 (0.68–0.95)	0.79 (0.60–1.04)	0.01
Multivariate HR (95% CI)^a	Ref.	0.89 (0.75–1.06)	0.92 (0.69–1.21)	0.21
H2RA use
No. of cases	1821	225	94
Person-years	2,652,702	378,358	111,387
Age-adjusted HR (95% CI)	Ref.	0.84 (0.73–0.97)	1.02 (0.82–1.25)	0.33
Multivariate HR (95% CI)^a	Ref.	0.91 (0.79–1.05)	1.09 (0.88–1.35)	0.95

BMI body mass index, CI confidence interval, HR hazards ratio, MHT menopausal hormone therapy, NHS Nurses’ Health Study, NHSII Nurses’ Health Study II.
^aAdjusted for age, BMI ( < 25 kg/m², 25–27.5 kg/m², 27.5–30 kg/m², ≥30 kg/m²) physical activity (<3 MET-h/week, 3–27 MET-h/week, ≥27 MET-h/week), family history of colorectal cancer (no, yes), alcohol intake (<5 g/day, 5–15 g/day, ≥15 g/day), pack-years of smoking (0, 1–10, ≥10 pack-years), history of lower endoscopy (never/ever), caloric intake (quintiles), vitamin D (quintiles), calcium intake (quintiles), regular aspirin use (no, yes), folate intake (quintiles), MHT use (premenopausal, postmenopausal never user, postmenopausal past user, postmenopausal current user) (NHS and NHSII only) and red meat as main dish (quintiles).

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