Table 2.

Multivariable associations of demographic and clinical factors with risk of colorectal cancer according to refined subsites in the NHS, NHS2, and HPFS^a.

Risk factors	Proximal colon cancer				Distal colon cancer			Rectum cancer			P for overall heterogeneityb	P for linear heterogeneityc
	Cecum	Ascending colon	Transverse colon	Overall	Descending colon	Sigmoid colon	Overall	Rectosigmoid	Rectum	Overall
	n=474	n=633	n=250	n=1357	n=221	n=750	n=971	n=202	n=528	n=730
Age, per 5 years
HR	1.43	1.62	1.45	1.51	1.42	1.39	1.39	1.32	1.37	1.36
95% CI	1.35–1.52	1.53–1.71	1.34–1.57	1.45–1.56	1.3–1.55	1.32–1.45	1.34–1.45	1.2–1.44	1.29–1.45	1.29–1.42	<0.001	0.04
Ptrend	1.43	1.62	1.45	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001
P for heterogeneity within major subsitesb				0.006			0.72			0.52
Female sex
HR	0.63	1.73	0.61	0.93	0.83	0.54	0.65	0.84	0.68	0.70
95% CI	0.51–0.78	1.40–2.15	0.51–0.72	0.81–1.05	0.6–1.16	0.41–0.72	0.56–0.76	0.61–1.17	0.56–0.84	0.59–0.84	<0.001	0.70
P	<.0001	<.0001	<.0001	0.24	0.27	<.0001	<.0001	0.31	0.0003	<.0001
P for heterogeneity within main subsitesb				<0.001			0.10			0.29
Family history of colorectal cancer
HR	1.55	1.66	1.86	1.65	1.22	1.46	1.41	1.26	1.10	1.14
95%CI	1.25–1.91	1.39–1.98	1.41–2.46	1.46–1.87	0.88–1.70	1.23–1.73	1.21–1.64	0.89–1.79	0.88–1.37	0.94–1.37	0.02	0.004
P	<0.001	<0.001	<0.001	<0.001	0.24	<.0001	<0.001	0.19	0.42	0.17
P for heterogeneity within main subsitesb				0.57			0.37			0.52
Endoscopic screening
HR	0.75	0.71	0.67	0.72	0.45	0.36	0.38	0.53	0.50	0.51
95% CI	0.54–1.03	0.53–0.94	0.41–1.08	0.59–0.87	0.24–0.83	0.25–0.51	0.28–0.51	0.30–0.94	0.34–0.72	0.37–0.69	0.02	0.005
P	0.07	0.02	0.10	<0.001	0.01	<0.001	<0.001	0.03	<0.001	<0.001
P for heterogeneity within main subsitesb				0.94			0.62			0.83
Regular aspirin use
HR	0.76	0.69	0.67	0.71	0.62	0.73	0.70	0.65	0.81	0.76
95% CI	0.63–0.92	0.58–0.81	0.51–0.87	0.63–0.79	0.46–0.83	0.62–0.85	0.61–0.80	0.47–0.88	0.68–0.98	0.65–0.89	0.65	0.51
P	0.005	<0.001	0.003	<0.001	<0.001	<0.001	<0.001	0.005	0.03	<0.001
P for heterogeneity within main subsitesb				0.76			0.39			0.14

^aAge- and cohort-stratified Cox proportional hazards model was used with further adjustment for race, height (continuous), family history of colorectal cancer (yes or no), history of lower gastrointestinal endoscopic screening (yes or no), body mass index (continuous), pack-years of smoking (continuous), physical activity (continuous), alcohol intake (continuous), and regular aspirin use (yes or no). When age and sex are the main exposures, the model was only adjusted for each other of the two variables.

^bOverall heterogeneity was tested by using the meta-regression method with a subsite-specific random effect term as a nominal variable.

^cLinear heterogeneity was tested by using the meta-regression method with a subsite-specific random effect term as an ordinal variable.