Risk of cancer in patients with constipation

Figures & data

Table 1 Characteristics of patients with a first-time hospital-based diagnosis of constipation in Denmark during 1978–2013

	N (%)
Overall	175,901 (100)
Sex
Female	104,106 (59)
Male	71,795 (41)
Type of hospital contact
Inpatient	125,377 (71)
Outpatient	40,478 (23)
Emergency room visit	10,046 (6)
Calendar period of constipation diagnosis
1978–1985	22,136 (13)
1986–1993	21,505 (13)
1994–2001	34,393 (20)
2002–2009	57,144 (33)
2010–2013	40,723 (23)
Age at diagnosis of constipation (years)
0–17	49,531 (28)
18–34	16,971 (10)
35–49	16,002 (9)
50–64	21,313 (12)
65+	72,084 (41)
Lower endoscopy^a	24,194 (13.8)
Surgery on the small intestine, colon, or anal canal^b	2,588 (1.5)
Modified Charlson Comorbidity Index score^c
Low	117,596 (67)
Moderate	45,305 (26)
Severe	13,000 (7)
Comorbidities
Diabetes mellitus	10,405 (6)
Parkinson’s disease or multiple sclerosis	3,202 (2)
Crohn’s disease or ulcerative colitis	5,692 (3)
Myxedema	1,371 (1)

Notes: ^aPerformed in the period from 3 months prior to 4 weeks following the constipation diagnosis. ^bPerformed in the period from 3 months prior to 3 months following the constipation diagnosis. ^cCategories of comorbidity were based on modified Charlson Comorbidity Index scores: 0, low; 1–2, moderate; ≥3, severe.

Table 3 Standardized incidence ratios for selected cancers in patients with a first-time hospital-based diagnosis of constipation, by sex, age group, calendar year, type of hospital contact, and comorbidity level, Denmark, 1978–2013

	Gastrointestinal cancers	Colorectal cancers	Other gastrointestinal cancers^a	Hormone-related cancers	Lymphomas
	0–1 years after constipation diagnosis
Total	5.0 (4.8–5.3)	5.2 (4.9–5.5)	4.8 (4.5–5.2)	2.1 (2.0–2.3)	3.4 (3.0–3.9)
Sex
Female	5.1 (4.7–5.4)	5.2 (4.8–5.7)	4.8 (4.3–5.3)	1.8 (1.7–2.0)	2.6 (2.0–3.2)
Male	5.0 (4.7–5.4)	5.1 (4.7–5.5)	4.9 (4.4–5.5)	2.5 (2.3–2.8)	4.3 (3.6–5.1)
Age group at constipation diagnosis (years)
0–17	13.6 (2.8–39.8)	–	15.9 (3.3–46.3)	8.7 (1.2–31.6)	14.8 (6.8–28.2)
18–34	28.8 (14.9–50.3)	34.4 (15.7–65.3)	19.4 (4.0–56.7)	2.8 (1.2–5.6)	3.4 (0.7–10.0)
35–49	12.2 (9.0–16.1)	13.1 (8.8–18.6)	11.0 (6.6–17.2)	1.7 (1.1–2.4)	7.8 (4.2–13.4)
50–64	9.9 (8.8–11.0)	10.0 (8.6–11.6)	9.7 (8.1–11.5)	1.9 (1.6–2.3)	5.3 (3.7–7.3)
≥65	4.5 (4.2–4.7)	4.6 (4.3–4.9)	4.2 (3.9–4.6)	2.2 (2.0–2.3)	2.9 (2.4–3.4)
Calendar year of constipation diagnosis
1978–1985	3.5 (3.1–4.1)	2.8 (2.3–3.4)	4.5 (3.7–5.4)	1.8 (1.4–2.2)	2.9 (1.8–4.5)
1986–1993	3.4 (2.9–3.9)	3.6 (3.0–4.3)	3.1 (2.4–3.9)	1.9 (1.5–2.3)	2.8 (1.7–4.2)
1994–2001	4.6 (4.1–5.1)	4.9 (4.2–5.5)	4.1 (3.4–5.0)	2.3 (2.0–2.7)	3.0 (2.1–4.2)
2002–2009	6.0 (5.6–6.5)	6.2 (5.6–6.7)	5.8 (5.1–6.6)	2.2 (2.0–2.5)	3.8 (3.0–4.7)
2010–2013	6.6 (5.9–7.2)	6.9 (6.1–7.8)	6.0 (5.0–7.0)	2.1 (1.8–2.5)	3.9 (2.9–5.1)
Type of hospital contact
Inpatient	5.0 (4.8–5.3)	5.1 (4.8–5.5)	4.8 (4.4–5.3)	2.1 (2.0–2.3)	3.5 (3.0–4.1)
Outpatient clinic	3.7 (3.2–4.2)	3.5 (2.9–4.2)	4.0 (3.2–5.0)	1.8 (1.5–2.1)	2.6 (1.7–3.7)
Emergency room	9.5 (8.2–11.0)	10.8 (9.0–12.8)	7.4 (5.5–9.7)	3.1 (2.4–3.9)	5.1 (3.0–8.2)
Modified Charlson Comorbidity Index score^b
Low (0)	6.3 (5.9–6.7)	6.8 (6.3–7.4)	5.5 (4.9–6.1)	2.5 (2.3–2.7)	4.3 (3.5–5.1)
Moderate (1–2)	4.2 (3.9–4.5)	4.0 (3.6–4.4)	4.6 (4.1–5.2)	1.9 (1.7–2.1)	2.6 (2.0–3.4)
High (3+)	3.3 (2.8–3.8)	3.2 (2.6–4.0)	3.3 (2.5–4.3)	1.6 (1.2–1.9)	2.9 (1.9–4.4)
	2–15 years after constipation diagnosis
Total	1.0 (1.0–1.1)	0.8 (0.8–0.9)	1.3 (1.2–1.4)	1.0 (0.9–1.0)	1.1 (1.0–1.2)
Sex
Female	1.0 (1.0–1.1)	0.8 (0.8–0.9)	1.3 (1.2–1.5)	1.0 (0.9–1.0)	1.1 (1.0–1.3)
Male	1.0 (0.9–1.1)	0.8 (0.8–0.9)	1.3 (1.1–1.4)	1.0 (0.9–1.0)	1.1 (0.9–1.3)
Age group at constipation diagnosis (years)
0–17	–	–	–	1.0 (0.9–1.9)	0.9 (0.4–1.7)
18–34	1.7 (1.0–2.8)	1.3 (0.6–2.6)	2.3 (1.1–4.2)	0.8 (0.6–1.0)	1.6 (0.9–2.6)
35–49	1.5 (1.2–1.8)	0.8 (0.6–1.2)	2.4 (1.8–3.0)	0.9 (0.8–1.1)	1.6 (1.1–2.3)
50–64	1.1 (1.0–1.2)	0.9 (0.8–1.1)	1.4 (1.2–1.6)	1.0 (0.9–1.1)	1.2 (0.9–1.5)
≥65	1.0 (0.9–1.0)	0.8 (0.8–0.9)	1.2 (1.1–1.3)	1.0 (0.9–1.0)	1.0 (0.9–1.2)
Calendar year of constipation diagnosis
1978–1985	1.1 (0.9–1.2)	1.0 (0.8–1.1)	1.2 (1.0–1.4)	1.0 (0.9–1.1)	1.2 (0.9–1.5)
1986–1993	1.1 (1.0–1.2)	0.9 (0.7–1.0)	1.4 (1.2–1.6)	0.9 (0.8–1.0)	1.1 (0.8–1.5)
1994–2001	0.9 (0.8–1.0)	0.7 (0.6–0.8)	1.3 (1.1–1.4)	1.0 (1.0–1.1)	1.2 (1.0–1.4)
2002–2009	1.0 (0.9–1.1)	0.8 (0.7–0.9)	1.4 (1.2–1.6)	0.9 (0.9–1.0)	1.0 (0.8–1.2)
2010–2013	1.1 (0.8–1.3)	1.0 (0.7–1.3)	1.2 (0.8–1.7)	1.0 (0.8–1.2)	1.1 (0.6–1.9)
Type of hospital contact
Inpatient	1.0 (1.0–1.1)	0.9 (0.8–0.9)	1.3 (1.2–1.4)	1.0 (0.9–1.0)	1.2 (1.0–1.3)
Outpatient clinic	0.9 (0.7–1.0)	0.7 (0.6–0.8)	1.2 (0.9–1.4)	1.0 (0.9–1.1)	1.0 (0.7–1.3)
Emergency room	1.1 (0.9–1.3)	0.8 (0.6–1.0)	1.5 (1.2–2.0)	0.9 (0.7–1.1)	0.8 (0.4–1.3)
Modified Charlson Comorbidity Index score^b
Low (0)	1.0 (0.9–1.1)	0.8 (0.8–0.9)	1.3 (1.2–1.4)	1.0 (0.9–1.0)	1.1 (1.0–1.3)
Moderate (1–2)	1.0 (0.9–1.1)	0.8 (0.7–0.9)	1.3 (1.1–1.5)	1.0 (0.9–1.1)	1.2 (0.9–1.4)
High (3+)	1.2 (1.0–1.4)	0.9 (0.7–1.1)	1.7 (1.3–2.1)	0.8 (0.7–1.0)	1.0 (0.6–1.6)

Notes: Insufficient for estimation, due to less than 5 observed cancer cases. ^aIncluding cancers of the esophagus, stomach, small intestine, anal canal, liver, gall bladder and biliary tract, pancreas, and other poorly specified gastrointestinal cancers. ^bComorbidities are specified in Table S2.

Figure 1 Cumulative incidence of gastrointestinal cancers in patients with a hospital-based diagnosis of constipation.^a

Notes:^aIncluding patients with a first-time hospital-based diagnosis of constipation in Denmark during 1978–2013, accounting for death as a competing risk.
Abbreviation: CI, confidence interval.

Table 4 Standardized incidence ratios for colorectal cancers in patients with a first-time hospital-based diagnosis of constipation, by presence/absence of a lower endoscopy performed in the period from 3 months prior to 4 weeks following the constipation diagnosis, Denmark, 1978–2013

	Colorectal cancers diagnosed ≥4 weeks – 1 year from constipation diagnosis^a			Colorectal cancers diagnosed ≥1 year from constipation diagnosis
	O	E	SIR (95% CI)	O	E	SIR (95% CI)
Endoscopy (N=24,194)	112	38.8	2.9 (2.4–3.5)	121	185.3	0.7 (0.5–0.8)
No Endoscopy (N=144,751)	451	168.0	2.7 (2.4–2.9)	734	837.3	0.9 (0.8–0.9)

Note: ^aFollow-up was initiated 4 weeks after the constipation diagnosis because the analysis was conditioned on lower endoscopy up until 4 weeks after the constipation diagnosis.

Abbreviations: CI, confidence interval; E, expected number of cases; O, observed number of cases; SIR, standardized incidence ratio.

Table 5 Standardized incidence ratios for cancer in patients with constipation by type of hospital diagnosis, Denmark, 1978–2013

	Cancers diagnosed 0–1 year after constipation diagnosis			Cancers diagnosed 2–15 years after constipation diagnosis
	O	E	SIR (95% CI)	O	E	SIR (95% CI)
Primary diagnosis
Gastrointestinal cancers	1401	249.2	5.6 (5.3–5.9)	1205	1184.8	1.0 (1.0–1.1)
Colorectal cancers	903	153.9	5.9 (5.5–6.3)	610	738.5	0.8 (0.8–0.9)
Other gastrointestinal cancers	498	95.2	5.2 (4.8–5.7)	595	446.3	1.3 (1.2–1.4)
Hormone-related cancers	602	282.6	2.1 (2.0–2.3)	1440	1487.6	1.0 (0.9–1.0)
Lymphoma	130	41.1	3.2 (2.7–3.8)	233	213.3	1.1 (1.0–1.2)
Secondary diagnosis
Gastrointestinal cancers	581	150.5	3.9 (3.6–4.2)	574	570.4	1.0 (0.9–1.1)
Colorectal cancers	346	93.4	3.7 (3.3–4.1)	311	355.6	0.9 (0.8–1.0)
Other gastrointestinal cancers	235	57.1	4.1 (3.6–4.7)	263	214.8	1.2 (1.1–1.4)
Hormone-related cancers	332	158.0	2.1 (1.9–2.3)	598	651.0	0.9 (0.9–1.0)
Lymphoma	84	23.5	3.6 (2.9–4.4)	110	95.9	1.2 (0.9–1.4)

Abbreviations: CI, confidence interval; E, expected number of cases; O, observed number of cases; SIR, standardized incidence ratio.

Figure 2 Cumulative incidence of selected non-gastrointestinal cancers in patients with a hospital-based diagnosis of constipation.^a

Notes: ^aSelected non-gastrointestinal cancers included hormone-related cancers and lymphoma in patients with a first-time hospital-based diagnosis of constipation in Denmark, 1978–2013, accounting for death as a competing risk.

Abbreviation: CI, confidence interval.

Table 2 Standardized incidence ratios for selected cancers in patients with a first-time hospital-based diagnosis of constipation in Denmark, 1978–2013

	0–1 year after constipation diagnosis			2–15 years after constipation diagnosis
Cancer site	O	E	SIR (95% CI)	O	E	SIR (95% CI)
Gastrointestinal cancers	1851	367.2	5.0 (4.8–5.3)	1658	1641.2	1.0 (1.0–1.1)
Colorectal cancers	1172	227.0	5.2 (4.9–5.5)	855	1022.6	0.8 (0.8–0.9)
Colon (incl. rectosigmoid cancers)	987	154.5	6.4 (6.0–6.8)	679	700.1	1.0 (0.9–1.1)
Rectum	185	72.6	2.6 (2.2–3.0)	176	322.5	0.6 (0.5–0.6)
Other gastrointestinal cancers	679	140.2	4.8 (4.5–5.2)	803	618.6	1.3 (1.2–1.4)
Esophagus	44	18.2	2.4 (1.8–3.3)	99	83.2	1.2 (1.0–1.5)
Stomach	138	38.0	3.6 (3.1–4.3)	179	155.2	1.2 (1.0–1.3)
Small intestine	38	3.7	10.2 (7.2–14)	36	17.5	2.1 (1.4–2.9)
Anal canal	9	4.0	2.3 (1.0–4.3)	29	20.7	1.4 (0.9–2.0)
Liver	64	15.2	4.2 (3.3–5.4)	115	68.0	1.7 (1.4–2.0)
Gall bladder and biliary tract	43	13.1	3.3 (2.4–4.4)	67	57.7	1.2 (0.9–1.5)
Pancreas	328	46.4	7.1 (6.3–7.9)	271	210.0	1.3 (1.1–1.5)
Other, poorly specified	15	1.6	9.7 (5.4–16)	7	6.4	1.1 (0.4–2.2)
Non-gastrointestinal cancers
Hormone-related cancers	859	404.4	2.1 (2.0–2.3)	1919	1999.3	1.0 (0.9–1.0)
Breast	192	172.4	1.1 (1.0–1.3)	972	952.6	1.0 (1.0–1.1)
Corpus uteri	48	33.5	1.4 (1.1–1.9)	137	175.5	0.8 (0.7–0.9)
Ovary	186	25.5	7.3 (6.3–8.4)	104	133.9	0.8 (0.6–0.9)
Prostate	420	164.6	2.6 (2.3–2.8)	646	685.7	0.9 (0.9–1.0)
Testes	5	2.8	1.8 (0.6–4.1)	19	20.1	1.0 (0.6–1.5)
Thyroid	8	5.5	1.5 (0.6–2.9)	41	31.6	1.3 (0.9–1.8)
Lymphomas	203	59.3	3.4 (3.0–3.9)	321	289.3	1.1 (1.0–1.2)
Hodgkin’s malignant lymphoma	9	3.2	2.8 (1.3–5.3)	23	21.0	1.1 (0.7–1.7)
Non-Hodgkin’s malignant lymphoma	194	56.1	3.5 (3.0–4.0)	298	268.4	1.1 (1.0–1.2)

Abbreviations: CI, confidence interval; E, expected number of cases; O, observed number of cases; SIR, standardized incidence ratio.

Table S1 Diagnosis and procedure codes used in the study

	ICD-8	ICD-10	Procedure codes (1978–1995)	Procedure codes (1996–2013)	Surgery codes
Constipation	564.00, 564.09	DK590
Cancers
Gastrointestinal cancers		DC15–26 (expect morphology codes 809,879)
Colorectal cancers		DC18–20
Other gastrointestinal cancers		DC15–17, DC21–26 (expect morphology codes 809,879)
Hormone-related cancers		DC50, DC54–56, DC61–62, DC73,
Lymphoma		DC81–85, DC90
Lower endoscopy			91070, 91080	KUJF32- KUJF35 KUJF42–45, KJFA15 – KJGA05
Surgery on the small intestine, colon, or anal canal					KJG, KJF
Inflammatory bowel disease (Crohn’s disease and ulcerative colitis and paralytic ileus)	563.19, 560.19, 563.01	K50, K51, K56
Diabetes	24900-25009, 25390, 27380	E10, E11, H36.0
Multiple sclerosis, Parkinson’s disease	340.00–340.09, 342.99, 34809	G20, G35
Myxedema	243.99–244.09	E03

Table S2 Codes for conditions included in the modified Charlson Comorbidity Index

Comorbidities	Weight	ICD-8	ICD-10
Myocardial infarction	1	410	I21; I22; I23
Congestive heart failure		427.09; 427.10; 427.11; 427.19; 428.99; 782.49	I50; I11.0; I13.0; I13.2
Peripheral vascular disease		440; 441; 442; 443; 444; 445	I70; I71; I72; I73; I74; I77
Cerebrovascular disease		430–438	I60-I69; G45; G46
Dementia		290.09-290.19; 293.09	F00-F03; F05.1; G30
Chronic pulmonary disease		490–493; 515-518	J40-J47; J60-J67; J68.4; J70.1; J70.3; J84.1; J92.0; J96.1; J98.2; J98.3
Connective tissue disease		712; 716; 734; 446; 135.99	M05; M06; M08; M09; M30; M31; M32; M33; M34; M35; M36; D86
Ulcer disease		530.91; 530.98; 531–534	K22.1; K25–K28
Mild liver disease		571; 573.01; 573.04	B18; K70.0–K70.3; K70.9; K71; K73; K74; K76.0
Diabetes without end-organ damage		249.00, 249.06, 249.07, 249.09, 250.00, 250.06, 250.07, 250.09	E10.0, E10.1, E10.9, E11.0, E11.1, E11.9
Diabetes with end-organ damage	2	249.01-249.05, 249.08, 250.01-250.05, 250.08	E10.2- E10.8, E11.2-E11.8
Hemiplegia		344	G81; G82
Moderate to severe renal disease		403; 404; 580–583; 584; 590.09; 593.19; 753.10–753.19; 792	I12; I13; N00–N05; N07; N11; N14; N17–N19; Q61
Moderate to severe liver disease	3	070.00; 070.02; 070.04; 070.06; 070.08; 573.00; 456.00-456.09	B15.0; B16.0; B16.2; B19.0; K70.4; K72; K76.6; I85
AIDS	6	079.83	B21–B24