Risk Factors for Inflammatory Bowel Disease in the General Population

L. A. García Rodríguez; A. González-Pérez; S. Johansson; M.-A. Wallander

Aliment Pharmacol Ther. 2005;22(4):309-315.

Abstract and Introduction

Background: The aetiology of inflammatory bowel disease remains largely unknown.
Aim: We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease.
Methods: We identified a cohort of patients 20–84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case–control analysis using all cases and a random sample of 10 000 frequency-matched controls.
Results: Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89–6.22) and CD (OR: 3.15; 95% CI: 1.24–7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04–6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14–1.00).
Conclusions: Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.

The incidence of inflammatory bowel disease (IBD) tends to plateau in those regions with the greatest incidence rates but is still growing in low-incidence areas such as southern Europe, Asia, and much of the developing world.^[1] Nevertheless the aetiology of the disease remains largely unknown. While some risk factors such as smoking have been studied in more detail, the impact of most other factors on the two main entities that constitute IBD, ulcerative colitis (UC) and Crohn's disease (CD) has not been established yet.

We conducted a prospective cohort study with a nested case–control analysis using data from the General Practice Research Database (GPRD) to identify risk factors associated with the occurrence of UC and CD in this population.

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Abstract and Introduction
Methods
Results
Discussion
References

Risk of UC and CD Associated With Selected Comorbidity and Prior Smoking Status
	UC cases (%) (n = 222)	CD cases (%) (n = 171)	Controls (%) (n = 10 000)	UC OR* (95% CI)	CD OR* (95% CI)
OA	36 (16.2)	35 (20.5)	1545 (15.5)	0.92 (0.62–1.38)	1.43 (0.92–2.23)
RA	5 (2.3)	8 (4.7)	112 (1.1)	2.16 (1.31–3.54)	4.38 (2.01–9.51)
Depression	44 (19.8)	28 (16.3)	1478 (14.8)	1.38 (0.95–2.00)	0.94 (0.59–1.48)
Anxiety	36 (16.2)	22 (12.9)	1200 (12)	1.33 (0.89–1.98)	0.96 (0.58–1.59)
Stress	8 (3.6)	8 (4.7)	368 (3.7)	0.80 (0.39–1.67)	1.17 (0.56–2.45)
Asthma	28 (12.6)	16 (9.4)	881 (8.8)	1.41 (0.93–2.15)	0.97 (0.57–1.67)
COPD	6 (2.7)	4 (2.3)	258 (2.6)	0.81 (0.34–1.94)	0.84 (0.29–2.41)
Diabetes	15 (6.8)	5 (2.9)	299 (3.0)	2.09 (1.20–3.66)	1.10 (0.44–2.75)
IBS^†	19 (8.6)	22 (13.0)	407 (4.1)	2.16 (1.31–3.54)	3.40 (2.11–5.47)
Smoking
non-smoker	130 (58.6)	74 (43.3)	5307 (53.1)	1	1
smoker	37 (16.7)	60 (35.1)	2379 (23.8)	0.61 (0.42–0.89)	1.74 (1.22–2.48)
ex-smoker	27 (12.2)	19 (11.1)	700 (7.0)	1.45 (0.94–2.23)	1.75 (1.01–3.00)
unknown	28 (12.6)	18 (10.5)	1614 (16.1)	0.71 (0.46–1.08)	0.80 (0.47–1.36)
Appendectomy	4 (1.8)	8 (4.7)	469 (4.7)	0.37 (0.14–1.00)	0.92 (0.45–1.91)

* Estimates adjusted for age, sex, calendar year, and all the variables in the table.
^†Prior history of IBS more than 1 year before the index date.
OA, osteoarthritis; RA, rheumatoid arthritis.

Risk of IBD Associated With NSAID Use
	IBD cases (%) (n = 444)	Controls (%) (n = 10000)	IBD OR* (95% CI)
Aspirin
Non-use	412 (92.8)	9294 (92.9)	1
Current use	16 (3.6)	400 (4.0)	0.76 (0.44–1.29)
<1 month	1 (0.2)	28 (0.3)	0.86 (0.11–6.40)
1–12 months	8 (1.8)	144 (1.4)	1.02 (0.46–2.23)
>1 year	7 (1.6)	228 (2.3)	0.60 (0.27–1.33)
Past use	16 (3.6)	306 (3.1)	1.05 (0.62–1.77)
NA-NSAIDs
Non-use	209 (47.1)	5057 (50.6)	1
Current use	47 (10.6)	625 (6.3)	1.38 (0.96–2.00)
<1 month	19 (4.3)	219 (2.2)	1.53 (0.92–2.55)
1–12 months	11 (2.5)	197 (2.0)	1.06 (0.55–2.05)
>1 year	17 (3.8)	209 (2.1)	1.45 (0.80–2.61)
Past use	188 (42.3)	4318 (43.2)	0.93 (0.75–1.15)
Paracetamol
Non-use	229 (51.6)	6022 (60.2)	1
Current use	58 (13.1)	699 (7.0)	2.02 (1.43–2.85)
<1 month	30 (6.8)	210 (2.1)	3.32 (2.15–5.14)
1–12 months	17 (3.8)	232 (2.3)	1.53 (0.87–2.68)
>1 year	11 (2.5)	257 (2.6)	0.90 (0.45–1.79)
Past use	157 (35.4)	3279 (32.8)	1.22 (0.98–1.53)

* Estimates adjusted for age, sex, calendar year, and all the variables in Table 1 and 2.

Risk of UC and CD Associated With OC and HRT Use
	UC cases (%) (n = 96)	CD cases (%) (n = 92)	Controls (%) (n = 5162)	UC OR* (95% CI)	CD OR* (95% CI)
OCs
Non-use	72 (75.0)	58 (63.0)	3669 (71.1)	1	1
Current use	11 (11.5)	14 (15.2)	410 (7.9)	1.58 (0.71–3.52)	1.94 (0.85–4.45)
<1 month	1 (1.0)	3 (3.3)	68 (1.3)	0.79 (0.10–6.09)	2.49 (0.66–9.36)
1–12 months	4 (4.2)	2 (2.2)	181 (3.5)	1.31 (0.42–4.11)	0.61 (0.13–2.87)
>1 year	6 (6.3)	9 (9.8)	161 (3.1)	2.35 (0.89–6.22)	3.15 (1.24–7.99)
Past use	13 (13.5)	20 (21.7)	1083 (21.0)	0.67 (0.32–1.39)	1.04 (0.50–2.17)
HRT
Non-use	84 (87.5)	71 (77.2)	4454 (86.3)	1	1
Current use	7 (7.3)	12 (13.0)	368 (7.1)	0.96 (0.41–2.25)	2.08 (1.00–4.38)
<1 month	1 (1.0)	1 (1.1)	51 (1.0)	0.99 (0.13–7.51)	1.13 (0.15–8.80)
1–12 months	2 (2.1)	4 (4.4)	133 (2.6)	0.76 (0.18–3.26)	1.97 (0.65–5.94)
>1 year	4 (4.2)	7 (7.6)	184 (3.6)	1.11 (0.38–3.26)	2.60 (1.04–6.49)
Past use	5 (5.2)	9 (9.8)	340 (6.6)	0.75 (0.29–1.98)	1.66 (0.71–3.86)

* Estimates adjusted for age, calendar year, and all the variables in Tables 1–3.

Risk of UC and CD Associated With OC and HRT Use
	UC cases (%) (n = 96)	CD cases (%) (n = 92)	Controls (%) (n = 5162)	UC OR* (95% CI)	CD OR* (95% CI)
OCs
Non-use	72 (75.0)	58 (63.0)	3669 (71.1)	1	1
Current use	11 (11.5)	14 (15.2)	410 (7.9)	1.58 (0.71–3.52)	1.94 (0.85–4.45)
<1 month	1 (1.0)	3 (3.3)	68 (1.3)	0.79 (0.10–6.09)	2.49 (0.66–9.36)
1–12 months	4 (4.2)	2 (2.2)	181 (3.5)	1.31 (0.42–4.11)	0.61 (0.13–2.87)
>1 year	6 (6.3)	9 (9.8)	161 (3.1)	2.35 (0.89–6.22)	3.15 (1.24–7.99)
Past use	13 (13.5)	20 (21.7)	1083 (21.0)	0.67 (0.32–1.39)	1.04 (0.50–2.17)
HRT
Non-use	84 (87.5)	71 (77.2)	4454 (86.3)	1	1
Current use	7 (7.3)	12 (13.0)	368 (7.1)	0.96 (0.41–2.25)	2.08 (1.00–4.38)
<1 month	1 (1.0)	1 (1.1)	51 (1.0)	0.99 (0.13–7.51)	1.13 (0.15–8.80)
1–12 months	2 (2.1)	4 (4.4)	133 (2.6)	0.76 (0.18–3.26)	1.97 (0.65–5.94)
>1 year	4 (4.2)	7 (7.6)	184 (3.6)	1.11 (0.38–3.26)	2.60 (1.04–6.49)
Past use	5 (5.2)	9 (9.8)	340 (6.6)	0.75 (0.29–1.98)	1.66 (0.71–3.86)

* Estimates adjusted for age, calendar year, and all the variables in Tables 1–3.

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