Table 2.

Night-shift work duration and colorectal cancer risk according to tumor IRS1 and IRS2 expression status in the NHS.

	Night-shift work duration
	Never	1–14 years	≥15 years	P_trend^a	P_{heterogeneity}^b
Total colorectal cancer in the full cohorts
No. cases (N = 1,397)	536	718	143
Age-adjusted HR (95% CI)	1 (ref)	1.01 (0.90–1.13)	1.28 (1.06–1.54)	0.008
Multivariable HR (95% CI)^c	1 (ref)	1.01 (0.90–1.13)	1.20 (0.99–1.45)	0.06
Total colorectal cancer among women with IRS1 data
No. cases (N = 304)	122	146	36
Age-adjusted HR (95% CI)	1 (ref)	0.91 (0.71–1.16)	1.42 (0.97–2.06)	0.05
Multivariable HR (95% CI)^c	1 (ref)	0.90 (0.70–1.14)	1.31 (0.89–1.91)	0.13
IRS1
Negative/weak
No. cases (N = 218)	90	105	23
Age-adjusted HR (95% CI)	1 (ref)	0.88 (0.66–1.17)	1.23 (0.77–1.94)	0.36	0.02
Multivariable HR (95% CI)^c	1 (ref)	0.87 (0.65–1.15)	1.13 (0.71–1.80)	0.56	0.02
Moderate/intense
No. cases (N = 86)	32	41	13
Age-adjusted HR (95% CI)	1 (ref)	0.98 (0.62–1.56)	1.96 (1.02–3.77)	0.03
Multivariable HR (95% CI)^c	1 (ref)	0.97 (0.61–1.54)	1.81 (0.94–3.48)	0.06
Total colorectal cancer among women with IRS2 data
No. cases (N = 308)	119	153	36
Age-adjusted HR (95% CI)	1 (ref)	0.98 (0.77–1.25)	1.46 (1.00–2.13)	0.04
Multivariable HR (95% CI)^c	1 (ref)	0.97 (0.76–1.23)	1.35 (0.92–1.97)	0.11
IRS2
Negative/weak
No. cases (N = 206)	90	98	18
Age-adjusted HR (95% CI)	1 (ref)	0.83 (0.62–1.11)	0.98 (0.59–1.63)	0.95	0.008
Multivariable HR (95% CI)^c	1 (ref)	0.83 (0.62–1.10)	0.90 (0.54–1.51)	0.72	0.008
Moderate/intense
No. cases (N = 102)	29	55	18
Age-adjusted HR (95% CI)	1 (ref)	1.46 (0.93–2.29)	2.92 (1.61–5.30)	0.0004
Multivariable HR (95% CI)^c	1 (ref)	1.42 (0.90–2.22)	2.69 (1.48–4.89)	0.001

Note: Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute HRs and 95% CIs. All analyses were stratified by age (in month) and year of questionnaire return.
Abbreviation: No., number.
↵^aLinear trend test using the median years of each category.
↵^bThe likelihood ratio test was used to test for the heterogeneity of the associations between night-shift work duration (median) and colorectal cancer risk according to the expression of IRS1 and IRS2 (ordinal).
↵^cMultivariable HRs were adjusted for age (in month), adult BMI (<25, 25–<27.5, 27.5–<30, or ≥30 kg/m²), smoking (0, 1–10, or >10 pack-years), history of colorectal cancer in a parent or sibling (yes or no), history of sigmoidoscopy/colonoscopy (yes or no), postmenopausal status and hormone use (premenopause, postmenopause and never use hormone, postmenopause and current use hormone, postmenopause and past use hormone), physical activity (<3, 3–<27, ≥27 METs—hours/week), regular aspirin use (yes or no), alcohol consumption (0 –<5, 5–<15, or ≥15 g/day), total intake of vitamin D, folate, calcium, red meat and processed meat (all in tertiles), sleep duration (<6 h, 6–<7 h, 7–<8 h, 8–<9 h, or ≥9 h), and history of type II diabetes (yes or no).