Effect of smoking on the risk of gastrointestinal cancer after cholecystectomy: A national population-based cohort study

Table 1 Baseline characteristics and comparison of demographics between the cholecystectomy group and matched control group

Variables	Cholecystectomy, n = 174874	Control, n = 174874	P value
Age in years	55.67 ± 13.3	55.67 ± 13.3	1.00
Age group by year interval			1.00
20-39	20268 (11.59)	20268 (11.59)
40-64	106983 (61.18)	106983 (61.18)
≥ 65	47623 (27.23)	47623 (27.23)
Male sex	90271 (51.62)	90271 (51.62)	1.00
Income status for lower 25% group	33800 (19.33)	37275 (21.32)	< 0.0001
Smoking status			< 0.0001
Non-smoker	107630 (61.55)	108326 (61.95)
Ex-smoker, current cessation	34449 (19.70)	30501 (17.44)
Current smoker	32795 (18.75)	36047 (20.61)
Alcohol consumption			< 0.0001
None	108368 (61.97)	98356 (56.24)
Moderate as < 30 g/day	57373 (32.81)	64303 (36.77)
Heavy as ≥ 30 g/day	9133 (5.22)	12215 (6.99)
Regular physical activity	34582 (19.78)	35684 (20.41)	< 0.0001
BMI in kg/m2	24.71 ± 3.47	23.98 ± 3.26	< 0.0001
BMI group by kg/m2 interval			< 0.0001
< 18.5	3761 (2.15)	5273 (3.02)
18.5-23.0	50768 (29.03)	63622 (36.38)
23.0-25.0	43277 (24.75)	43801 (25.05)
25.0-30.0	64760 (37.03)	54738 (31.30)
≥ 30.0	12308 (7.04)	7440 (4.25)
Diabetes mellitus	29666 (16.96)	23076 (13.20)	< 0.0001
Hypertension	68635 (39.25)	61008 (34.89)	< 0.0001
Dyslipidemia	52115 (29.80)	48351 (27.65)	< 0.0001
Chronic kidney disease1	11414 (6.53)	9344 (5.34)	< 0.0001

¹Defined as estimated glomerular filtration rate of < 60 mL/minute/1.73 m².

Data are presented as n (%) or mean ± SD. BMI: Body mass index.

Table 2 Incidence rate and hazard ratio for the risk of colorectal cancer and gastric cancer after cholecystectomy

Cancer	Cholecystectomy	No.	Event	Duration1	IR2	HR (95%CI)
						Model 1	P value	Model 2	P value	Model 3	P value
CRC	No (control)	174874	1018	736081	1.38	1 (Ref.)	0.0005	1 (Ref.)	0.0004	1 (Ref.)	0.0013
	Yes	174874	1152	718563	1.60	1.16 (1.07-1.26)		1.16 (1.07-1.27)		1.15 (1.06-1.25)
GC	No (control)	174874	881	736344	1.20	1 (Ref.)	0.017	1 (Ref.)	0.015	1 (Ref.)	0.027
	Yes	174874	960	718935	1.34	1.12 (1.02-1.23)		1.12 (1.02-1.23)		1.11 (1.01-1.22)

¹Person-years.

²Per 1000 person-years.

Model 1 was not adjusted; Model 2 was adjusted for age and sex; Model 3 was adjusted for age, sex, smoking status, alcohol consumption, regular physical activity, hypertension, diabetes mellitus, dyslipidemia, body mass index, and estimated glomerular filtration rate. CRC: Colorectal cancer; GC: Gastric cancer; HR: Hazard ratio; IR: Incidence rate.

Table 3 Incidence rate and hazard ratio for the risk of colorectal cancer and gastric cancer after cholecystectomy according to smoking habits

Parameter		Colorectal cancer				Gastric cancer
		IR1	HR (95%CI)			IR1	HR (95%CI)
			Model 1	Model 2	Model 3		Model 1	Model 2	Model 3
Smoking status	Non-smoker	1.46	1 (Ref.)	1 (Ref.)	1 (Ref.)	1.04	1 (Ref.)	1 (Ref.)	1 (Ref.)
	Ex-smoker	2.15	1.48 (1.29-1.70)	1.33 (1.12-1.57)	1.35 (1.14-1.60)	2.10	2.01 (1.74-2.34)	1.15 (0.97-1.36)	1.19 (1.00-1.40)
	Current smoker	1.52	1.04 (0.89-1.22)	1.38 (1.15-1.66)	1.40 (1.16-1.69)	1.51	1.45 (1.23-1.71)	1.33 (1.10-1.60)	1.35 (1.12-1.64)
	P value		< 0.0001	0.0005	0.0002		< 0.0001	0.0110	0.0064
Smoking quantity	Non-smoker	1.46	1 (Ref.)	1 (Ref.)	1 (Ref.)	1.04	1 (Ref.)	1 (Ref.)	1 (Ref.)
	0 < pack-years < 10	1.30	0.89 (0.73-1.09)	1.2 (0.98-1.53)	1.26 (1.01-1.57)	1.11	1.06 (0.85-1.32)	1.03 (0.81-1.30)	1.06 (0.84-1.35)
	10 ≤ pack-years < 20	1.41	0.97 (0.79-1.19)	1.16 (0.92-1.46)	1.19 (0.94-1.50)	1.33	1.27 (1.03-1.58)	1.01 (0.80-1.28)	1.05 (0.83-1.33)
	20 ≤ pack-years < 30	1.96	1.35 (1.09-1.66)	1.39 (1.10-1.75)	1.41 (1.12-1.78)	2.10	2.01 (1.63-2.48)	1.33 (1.06-1.70)	1.37 (1.09-1.72)
	30 ≤ pack-years	3.03	2.08 (1.77-2.45)	1.59 (1.31-1.92)	1.59 (1.31-1.93)	3.14	3.00 (2.53-3.55)	1.42 (1.18-1.71)	1.43 (1.19-1.73)
	P value		< 0.0001	< 0.0001	< 0.0001		< 0.0001	0.0010	0.0010

¹Per 1000 person-years.

Model 1 was not adjusted; Model 2 was adjusted for age and sex; Model 3 was adjusted for age, sex, alcohol consumption, regular physical activity, hypertension, diabetes mellitus, dyslipidemia, body mass index, and estimated glomerular filtration rate. HR: Hazard ratio; IR: Incidence rate.

Table 4 Subgroup analysis according to smoking status and quantity in patients who underwent cholecystectomy

Variables		Colorectal cancer						Gastric cancer
		Age			Sex			Age			Sex
			IR1	Adjusted HR (95%CI)		IR1	Adjusted HR (95%CI)		IR1	Adjusted HR (95%CI)		IR1	Adjusted HR (95%CI)
Smoking status	Non-smoker	< 65 years	0.96	1 (Ref.)	Male	1.82	1 (Ref.)	< 65 years	0.58	1 (Ref.)	Male	2.06	1 (Ref.)
	Ex-smoker		1.32	1.27 (0.97-1.65)		2.22	1.35 (1.13-1.62)		1.13	1.11 (0.84-1.46)		2.20	1.21 (1.02-1.44)
	Current smoker		0.95	1.14 (0.87-1.49)		1.52	1.45 (1.18-1.79)		1.01	1.36 (1.03-1.80)		1.66	1.44 (1.18-1.76)
	Non-smoker	≥ 65 years	2.62	1 (Ref.)	Female	1.32	1 (Ref.)	≥ 65 years	2.12	1 (Ref.)	Female	0.68	1 (Ref.)
	Ex-smoker		4.20	1.39 (1.12-1.73)		1.09	1.14 (0.59-2.21)		4.45	1.19 (0.97-1.47)		0.48	1.06 (0.39-2.86)
	Current smoker		5.36	1.87 (1.44-2.42)		1.56	1.72 (1.11-2.67)		4.90	1.37 (1.05-1.78)		0.28	0.67 (0.25-1.82)
Smoking quantity	Non-smoker	< 65 years	0.96	1 (Ref.)	Male	1.82	1 (Ref.)	< 65 years	0.58	1 (Ref.)	Male	2.06	1 (Ref.)
	0 < pack-years < 10		0.85	1.18 (0.87-1.60)		1.35	1.29 (1.01-1.65)		0.67	1.13 (0.80-1.59)		1.29	1.11 (0.86-1.42)
	10 ≤ pack-years < 20		0.87	1.02 (0.73-1.42)		1.43	1.24 (0.98-1.58)		0.85	1.09 (0.77-1.53)		1.37	1.08 (0.85-1.37)
	20 ≤ pack-years < 30		1.11	1.14 (0.79-1.62)		1.94	1.40 (1.10-1.78)		1.16	1.24 (0.87-1.78)		2.16	1.42 (1.12-1.78)
	30 ≤ pack-years		2.03	1.50 (1.10-2.04)		2.97	1.52 (1.25-1.86)		2.06	1.43 (1.05-1.95)		3.16	1.45 (1.19-1.75)
	Non-smoker	≥ 65 years	2.62	1 (Ref.)	Female	1.32	1 (Ref.)	≥ 65 years	2.12	1 (Ref.)	Female	0.68	1 (Ref.)
	0 < pack-years < 10		4.07	1.40 (1.01-1.93)		1.06	1.27 (0.78-2.08)		3.81	1.09 (0.79-1.52)		0.31	0.83 (0.34-2.03)
	10 ≤ pack-years < 20		4.16	1.45 (1.06-1.99)		1.02	0.91 (0.34-2.44)		3.77	1.06 (0.77-1.46)		0.51	0.94 (0.23-3.80)
	20 ≤ pack-years < 30		5.10	1.71 (1.26-2.34)		2.83	2.33 (0.87-6.25)		5.56	1.50 (1.12-2.01)		0
	30 ≤ pack-years		4.75	1.57 (1.22-2.02)		6.76	4.57 (2.03-10.28)		4.98	1.30 (1.02-1.65)		1.11	1.42 (0.20-10.12)

¹Per 1000 person-years.

Hazard ratio was adjusted for age, sex, alcohol consumption, regular physical activity, hypertension, diabetes mellitus, dyslipidemia, body mass index, and estimated glomerular filtration rate. IR: Incidence rate; HR: Hazard ratio.