Increased risk of colorectal cancer in young males with higher cardiovascular risk: A nationwide population-based cohort study

Table 1 Risk of colorectal cancer according to cardiovascular risk score

	Risk score	n	Events	Person years	IRa	Model 1 HR (95%CI)	Model 2 HR (95%CI)	Model 3 HR (95%CI)	Model 4 HR (95%CI)
Total	0	1125969	7898	11544364	0.68	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
	1	775642	9612	7856740	1.22	1.788 (1.736-1.842)	0.949 (0.919-0.980)	0.936 (0.906-0.966)	0.938 (0.908-0.968)
	2	451302	8563	4492913	1.91	2.788 (2.704-2.874)	1.049 (1.014-1.086)	1.022 (0.987-1.058)	1.027 (0.992-1.064)
	≥ 3	173715	4256	1697936	2.51	3.671 (3.536-3.810)	1.188 (1.139-1.238)	1.147 (1.100-1.197)	1.155 (1.107-1.205)
	P for trend					< 0.001	< 0.001	< 0.001	< 0.001
Male	0	426624	2512	4363981	0.58	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
	1	522624	5920	5289246	1.12	1.944 (1.856-2.037)	1.135 (1.082-1.191)	1.116 (1.064-1.170)	1.117 (1.065-1.171)
	2	325451	6093	3238870	1.88	3.269 (3.120-3.424)	1.283 (1.222-1.346)	1.241 (1.182-1.304)	1.247 (1.187-1.309)
	≥ 3	138611	3462	1353225	2.56	4.449 (4.226-4.684)	1.421 (1.346-1.499)	1.356 (1.284-1.433)	1.367 (1.294-1.444)
	P for trend					< 0.001	< 0.001	< 0.001	< 0.001
Female	0	699345	5386	7180383	0.75	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
	1	253018	3692	2567494	1.44	1.917 (1.839-1.999)	0.987 (0.941-1.035)	0.968 (0.923-1.015)	0.967 (0.922-1.015)
	2	125851	2470	1254042	1.97	2.629 (2.506-2.757)	1.019 (0.963-1.077)	0.984 (0.929-1.042)	0.984 (0.929-1.042)
	≥ 3	35104	794	344712	2.30	3.078 (2.857-3.316)	1.093 (1.008-1.185)	1.049 (0.966-1.139)	1.049 (0.966-1.139)
	P for trend					< 0.001	0.074	0.640	0.650

^aColorectal cancer incidence rate per 1000 person-years.

Model 1: Not adjusted; Model 2: Adjusted for sex and age; Model 3: Adjusted for sex, age, alcohol consumption, regular exercise, body mass index, diabetes mellitus, and previous history of percutaneous coronary intervention or coronary artery bypass graft, myocardial infarction, stroke, and aneurysm of abdominal aorta; Model 4: Adjusted for sex, age, alcohol consumption, regular exercise, body mass index, diabetes mellitus, previous history of percutaneous coronary intervention or coronary artery bypass graft, myocardial infarction, stroke, aneurysm of abdominal aorta, and statin use; IR: Incidence rate; HR: Hazard ratio; CI: Confidence interval.

Table 2 Risk of colorectal cancer according to cardiovascular risk score when subdivided by age

Gender	Age	Risk score	n	Events	Person years	IRa	Model 1 HR (95%CI)	Model 2 HR (95%CI)	Model 3 HR (95%CI)	Model 4 HR (95%CI)
Total	< 50 years	0	893565	4125	9184868	0.45	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	433525	2079	4447577	0.47	1.041 (0.987-1.097)	1.043 (0.984-1.105)	1.027 (0.969-1.089)	1.028 (0.970-1.090)
		2	161618	1090	1653286	0.66	1.468 (1.374-1.570)	1.177 (1.090-1.270)	1.147 (1.062-1.238)	1.151 (1.066-1.243)
		≥ 3	42156	469	428824	1.09	2.437 (2.215-2.682)	1.506 (1.355-1.673)	1.448 (1.301-1.610)	1.460 (1.312-1.625)
		P for trend					< 0.001	< 0.001	< 0.001	< 0.001
	≥ 50 years	0	232404	3773	2359496	1.60	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	342117	7533	3409163	2.21	1.382 (1.329-1.437)	0.976 (0.937-1.016)	0.963 (0.925-1.003)	0.965 (0.927-1.005)
		2	289684	7473	2839626	2.63	1.647 (1.583-1.712)	1.045 (1.003-1.089)	1.017 (0.976-1.061)	1.022 (0.980-1.065)
		≥ 3	131559	3787	1269112	2.98	1.868 (1.786-1.954)	1.122 (1.070-1.176)	1.080 (1.029-1.134)	1.086 (1.034-1.140)
		P for trend					< 0.001	< 0.001	< 0.001	< 0.001
	P for interaction						< 0.001	< 0.001	< 0.001	< 0.001
Male	< 50 years	0	380916	1284	3914571	0.33	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	361592	1587	3708820	0.43	1.305 (1.212-1.404)	1.044 (0.969-1.125)	1.023 (0.949-1.103)	1.024 (0.950-1.103)
		2	152047	1024	1554993	0.66	2.008 (1.850-2.180)	1.142 (1.047-1.246)	1.101 (1.008-1.202)	1.105 (1.012-1.206)
		≥ 3	41490	463	422036	1.10	3.348 (3.010-3.723)	1.398 (1.248-1.566)	1.319 (1.176-1.481)	1.333 (1.188-1.497)
		P for trend					< 0.001	< 0.001	< 0.001	< 0.001
	≥ 50 years	0	45708	1228	449410	2.73	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	161032	4333	1580426	2.74	1.003 (0.942-1.069)	1.004 (0.942-1.070)	1.004 (0.942-1.070)	1.005 (0.944-1.071)
		2	173404	5069	1683877	3.01	1.102 (1.035-1.173)	1.089 (1.023-1.159)	1.075 (1.010-1.145)	1.080 (1.015-1.151)
		≥ 3	97121	2999	931189	3.22	1.180 (1.104-1.261)	1.165 (1.090-1.245)	1.137 (1.062-1.216)	1.146 (1.071-1.226)
		P for trend					< 0.001	< 0.001	< 0.001	< 0.001
	P for interaction						< 0.001	< 0.001	< 0.001	< 0.001
Female	< 50 years	0	512649	2841	5270298	0.54	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	71933	492	738757	0.67	1.235 (1.122-1.359)	1.027 (0.933-1.131)	1.015 (0.921-1.118)	1.015 (0.921-1.118)
		2	9571	66	98293	0.67	1.244 (0.975-1.588)	0.932 (0.730-1.190)	0.907 (0.710-1.161)	0.907 (0.709-1.161)
		≥ 3	666	6	6788	0.88	1.650 (0.743-3.665)	1.123 (0.504-2.502)	1.086 (0.487-2.422)	1.085 (0.486-2.422)
		P for trend					< 0.001	0.891	0.851	0.850
	≥ 50 years	0	186696	2545	1910086	1.33	1 (Ref.)	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	181085	3200	1828737	1.75	1.314 (1.248-1.385)	1.007 (0.953-1.064)	0.990 (0.937-1.046)	0.990 (0.936-1.046)
		2	116280	2404	1155749	2.08	1.563 (1.479-1.653)	1.070 (1.007-1.137)	1.034 (0.972-1.100)	1.034 (0.971-1.100)
		≥ 3	34438	788	337923	2.33	1.754 (1.620-1.900)	1.153 (1.060-1.254)	1.106 (1.015-1.205)	1.105 (1.014-1.204)
		P for trend					< 0.001	< 0.001	0.022	0.024
	P for interaction						0.256	0.218	0.339	0.338

^aColorectal cancer incidence rate per 1000 person-years.

Model 1: Not adjusted; Model 2: Adjusted for sex and age; Model 3: Adjusted for sex, age, alcohol consumption, regular exercise, body mass index, diabetes mellitus, and previous history of percutaneous coronary intervention or coronary artery bypass graft, myocardial infarction, stroke, and aneurysm of abdominal aorta; Model 4: Adjusted for sex, age, alcohol consumption, regular exercise, body mass index, diabetes mellitus, previous history of percutaneous coronary intervention or coronary artery bypass graft, myocardial infarction, stroke, aneurysm of abdominal aorta, and statin use; IR: Incidence rate; HR: Hazard ratio; CI: Confidence interval.

Table 3 Risk of colorectal cancer according to cardiovascular risk score when subdivided by statin use

		Risk score	n	Events	Person years	IRa	Model 1 HR (95%CI)	Model 2 HR (95%CI)	Model 3 HR (95%CI)
Total	Statin (-)	0	1095789	7504	11237006	0.67	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	721199	8615	7310810	1.18	1.765 (1.711-1.820)	0.944 (0.913-0.976)	0.932 (0.902-0.964)
		2	388601	7217	3874060	1.86	2.791 (2.702-2.883)	1.061 (1.023-1.100)	1.035 (0.998-1.074)
		≥ 3	138158	3366	1352131	2.49	3.735 (3.587-3.890)	1.200 (1.147-1.255)	1.160 (1.108-1.214)
		P for trend					< 0.001	< 0.001	< 0.001
	Statin (+)	0	30180	394	307358	1.28	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	54443	997	545930	1.83	1.425 (1.268-1.602)	0.991 (0.880-1.117)	0.972 (0.862-1.095)
		2	62701	1346	618852	2.17	1.698 (1.518-1.900)	1.003 (0.892-1.127)	0.974 (0.865-1.096)
		≥ 3	35557	890	345805	2.57	2.010 (1.785-2.263)	1.145 (1.010-1.297)	1.103 (0.972-1.253)
		P for trend					< 0.001	0.010	0.046
	P for interaction						< 0.001	0.036	0.071
Male	Statin (-)	0	418317	2395	4280007	0.56	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	500104	5515	5065266	1.09	1.946 (1.854-2.041)	1.144 (1.090-1.202)	1.126 (1.072-1.182)
		2	293142	5368	2922285	1.84	3.283 (3.129-3.445)	1.306 (1.242-1.373)	1.264 (1.201-1.329)
		≥ 3	113465	2807	1109737	2.53	4.525 (4.285-4.779)	1.443 (1.363-1.528)	1.374 (1.297-1.456)
		P for trend					< 0.001	< 0.001	< 0.001
	Statin (+)	0	8307	117	83974	1.39	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	22520	405	223980	1.81	1.298 (1.057-1.594)	0.889 (0.723-1.093)	0.870 (0.707-1.070)
		2	32309	725	316586	2.29	1.644 (1.352-1.998)	0.954 (0.783-1.163)	0.928 (0.760-1.132)
		≥ 3	25146	655	243488	2.69	1.931 (1.586-2.351)	1.107 (0.907-1.350)	1.067 (0.873-1.305)
		P for trend					< 0.001	0.003	0.011
	P for interaction						< 0.001	0.004	0.006
Female	Statin (-)	0	677472	5109	6956999	0.73	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	221095	3100	2245544	1.38	1.880 (1.798-1.965)	0.962 (0.914-1.012)	0.946 (0.899-0.995)
		2	95459	1849	951776	1.94	2.647 (2.510-2.792)	1.001 (0.941-1.065)	0.973 (0.913-1.036)
		≥ 3	24693	559	242394	2.31	3.148 (2.885-3.435)	1.069 (0.973-1.174)	1.033 (0.939-1.136)
		P for trend					< 0.001	0.408	0.868
	Statin (+)	0	21873	277	223384	1.24	1 (Ref.)	1 (Ref.)	1 (Ref.)
		1	31923	592	321950	1.84	1.484 (1.287-1.712)	1.150 (0.992-1.333)	1.130 (0.975-1.311)
		2	30392	621	302266	2.05	1.659 (1.440-1.912)	1.140 (0.980-1.327)	1.109 (0.951-1.293)
		≥ 3	10411	235	102317	2.30	1.856 (1.559-2.208)	1.241 (1.033-1.491)	1.199 (0.996-1.443)
		P for trend					< 0.001	0.047	0.126
	P for interaction						< 0.001	0.521	0.534

^aColorectal cancer incidence rate per 1000 person-years.

Model 1: Not adjusted; Model 2: Adjusted for sex and age; Model 3: Adjusted for sex, age, alcohol consumption, regular exercise, body mass index, diabetes mellitus, and previous history of percutaneous coronary intervention or coronary artery bypass graft, myocardial infarction, stroke, and aneurysm of abdominal aorta.