Table 2.

Estimated associations of early-onset colorectal cancer (EOCRC) incidence with smoking, alcohol consumption, and calcium intake (using SEER 9 data; age groups: 25-49). Five models (2^nd column) were used to estimate incidence rate ratio (IRR) of EOCRC for each unit/quintile change in each study factor (1^st column). Of the five models, the no-lag and lagged models used study factor levels defined by quintile (3^rd column) as input and estimated the IRR for each quintile, relative to the first quintile (i.e., the reference); the age-mean centering (AMC) models used continuous values as input and estimated the IRR for each unit change of the study factor. Of note, the estimated IRRs before and after AMC are not comparable because the exposure was on different scales. p-values, and ΔBIC and assessment of the strength of evidence (see details in main text) are also shown for each model.

			Men					Women
Study Factor	Method	Quintile	IRR (95% CI)	p-value (quintiles)	p-value (cont.)a	ΔBIC	Evidence	IRR (95% CI)	p-value (quintiles)	p-value (cont.)a	ΔBIC	Evidence
Smoking	No-lag	1	1		<0.001	2	Positive	1		<0.001	−5.4	No Improvement
		2	0.92 (0.82-1.04)	0.21				1.13 (0.99-1.28)	0.07
		3	0.98 (0.87-1.10)	0.71				1.20 (1.06-1.37)**	0.005
		4	1.11 (0.95-1.29)	0.19				1.28 (1.11-1.48)***	<0.001
		5	1.26 (1.04-1.53)*	0.02				1.37 (1.13-1.66)**	0.002
	Lagged	1	1		<0.001	−0.9	No Improvement	1		<0.001	7.7	Strong
		2	1.12 (1.02-1.24)*	0.02				1.15 (1.07-1.24)***	<0.001
		3	1.13 (1.01-1.27)*	0.03				1.19 (1.07-1.32)**	0.002
		4	1.21 (1.06-1.37)**	0.004				1.26 (1.10-1.43)***	<0.001
		5	1.33 (1.14-1.55)***	<0.001				1.39 (1.18-1.62)***	<0.001
	AMC no-lag		1.14 (1.05-1.23)***		<0.001	6.1	Strong	1.12 (1.03-1.21)**		0.005	3.3	Positive
	AMC lagged		1.17 (1.10-1.24)***		<0.001	21.4	Very Strong	1.15 (1.09-1.21)***		<0.001	21	Very Strong
	AMC cumulative		1.20 (1.13-1.29)***		<0.001	24.9	Very Strong	1.19 (1.12-1.27)***		<0.001	27.8	Very Strong
Alcohol	No-lag	1	1		0.5	−15.5	No Improvement	1		0.81	−4.9	No Improvement
		2	0.98 (0.88-1.09)	0.72				0.87 (0.78-0.96)**	0.009
		3	1.02 (0.91-1.15)	0.69				0.87 (0.77-0.97)*	0.01
		4	0.99 (0.89-1.11)	0.92				0.98 (0.89-1.09)	0.76
		5	1.03 (0.92-1.16)	0.57				0.92 (0.83-1.03)	0.14
Alcohol	Lagged	1	1		<0.001	8.1	Strong	1		<0.001	16.3	Very Strong
		2	1.10 (0.97-1.24)	0.13				1.04 (0.94-1.15)	0.45
		3	1.17 (1.05-1.31)**	0.005				1.02 (0.91-1.13)	0.77
		4	1.27 (1.13-1.43)***	<0.001				1.15 (1.05-1.26)**	0.003
		5	1.28 (1.13-1.46)***	<0.001				1.23 (1.11-1.37)***	<0.001
	AMC no-lag		1.03 (1-1.06)*		0.03	0.3	Weak	1 (0.97-1.04)		0.81	−4.2	No Improvement
	AMC lagged		1.08 (1.04-1.12)***		<0.001	11.3	Very Strong	1.08 (1.04-1.11)***		<0.001	15.6	Very Strong
	AMC cumulative		1.06 (1.03-1.09)***		<0.001	14.5	Very Strong	1.07 (1.04-1.11)***		<0.001	17.7	Very Strong
Calcium	No-lag	1	1		0.44	6	Positive	1		0.008	16.2	Very Strong
		2	0.91 (0.81-1.01)	0.08				0.87 (0.78-0.98)*	0.02
		3	0.85 (0.74-0.97)*	0.01				0.81 (0.71-0.92)**	0.001
		4	0.88 (0.76-1.03)	0.1				0.74 (0.62-0.87)***	<0.001
		5	0.96 (0.77-1.19)	0.69				0.80 (0.63-1.01)	0.06
	Lagged	1	1		0.29	−3.7	No Improvement	1		0.04	13.5	Very Strong
		2	0.86 (0.77-0.96)**	0.006				0.92 (0.83-1.02)	0.12
		3	0.84 (0.74-0.97)*	0.02				0.80 (0.70-0.91)***	<0.001
		4	0.85 (0.73-0.99)*	0.04				0.81 (0.69-0.95)**	0.01
		5	0.85 (0.70-1.04)	0.12				0.90 (0.73-1.10)	0.31
	AMC no-lag		1 (0.96-1.04)		0.86	−4.2	No Improvement	0.90 (0.84-0.97)**		0.008	2.2	Positive
	AMC lagged		0.98 (0.95-1.01)		0.12	−1.4	No Improvement	1.03 (0.95-1.11)		0.46	−3.3	No Improvement
	AMC cumulative		0.98 (0.94-1.02)		0.33	−3.1	No Improvement	0.98 (0.90-1.06)		0.6	−3.8	No Improvement

^*P<0.05

^**P<0.01

^***P<0.001; IRR=Incidence rate ratio; BIC=Bayesian information criterion; AMC=Age-mean centering.

IRRs were adjusted for age, period, and race.

^aFor the no-lag and lagged models, we generated p-value (cont.) by treating the median of the quintiles as a continuous variable in regression.