Chemoprevention of Colorectal Cancer in Inflammatory Bowel Disease

Sung-hee Han; Jonghun Lee

doi:10.4166/kjg.2014.63.1.3

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Han and Lee: Chemoprevention of Colorectal Cancer in Inflammatory Bowel Disease

Review Article

Korean J Gastroenterol 2014;63(1):3-10.

Published online: 4 October 2014

DOI: https://doi.org/10.4166/kjg.2014.63.1.3

Chemoprevention of Colorectal Cancer in Inflammatory Bowel Disease

Sung-hee Han, Jonghun Lee

Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea

Correspondence to: Jonghun Lee, Department of Internal Medicine, Dong-A University College of Medicine, 32 Daesingongwon-ro, Seo-gu, Busan 602-714, Korea. Tel: +82-51-240-5625, Fax: +82-51-242-5852, E-mail: jh2002@dau.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The risk of developing colorectal cancer is increased in patients with inflammatory bowel disease. Surveillance colonoscopy has not been shown to prolong survival and rates of interval cancer are reported to be high. Continuing colonic inflammation has been shown to be important in the development of colorectal cancer and therefore anti-inflammatory agents such as the 5-aminosalicylates and immunomodulators have been considered as potential chemopreventive agents. This review focuses on various chemopreventive agents that have been clearly shown to reduce the risk of colorectal adenoma and cancer in the patients with inflammatory bowel disease.

Keywords: Chemoprevention, Inflammatory bowel diseases, Colorectal neoplasms

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Table 1.

Studies Evaluating the Role of 5-Aminosalicylates (5-ASA) in the Chemoprevention of Dysplasia/Cancer in Patients with Inflammatory Bowel Disease

First author	Year	Design	Patient (n)	Agent	OR/RR (95% CI)	p-value
Case control and hospital based cohort studies
Rubin¹⁹	2006	Case control	124	5-ASA ＞1.2 g	0.28 (0.09–0.85)	0.011
Siegel²⁰	2006	Case control	54	5-ASA ＞1 yr	0.30 (0.05–1.17)	0.10
Velayos²¹	2006	Case control	376	5-ASA ＞1 yr	0.4 (0.2–0.9) ＜	＜0.05
Gupta²³	2007	Retrospective cohort	418	5-ASA ＞4 mo	0.5 (0.1–2.4)	NS
Ullman²²	2008	Retrospective cohort	311	5-ASA (yes vs. no)	0.7 (0.20–2.44)	NS
Tang²⁴	2010	Case control	48	5-ASA cumulative dose＞4,500 g	0.024 (0.0–0.65)	0.047
Population based cohort studies
Jess²⁵	2007	Population based case contro	l 145	5-ASA ＞1.2 g/day	1.6 (0.3–7.1)	NS
Terdiman²⁶	2007	Population based case contro	l 1,536	5-ASA (yes or no)	0.97 (0.77–1.23)	NS
Baars²⁷	2011	Population based case control	566	5-ASA (yes or no)	0.73 (0.42–1.27)	NS
Bernstein¹⁷	2011	Population based cohort	8,744	5-ASA ＞1 yr	1.04 (0.67–1.62)	0.87
		Population based case contro	l 404	5-ASA ＞1 yr	1.02 (0.60–1.74)	0.95
van Schaik²⁸	2012	Population based cohort	2,578	5-ASA ＞1.2 g/day for 6 mo	0.56 (0.22–1.40)	NS

Table 2.

Studies Evaluating the Role of Corticosteroids in the Chemoprevention of Dysplasia/Cancer in Inflammatory Bowel Disease

First author	Year	Design	Patient (n)	Agent	OR/RR (95% CI)	p-value
Lashner¹⁰	1997	Retrospective cohort	98	Any steroid use ＞6 mo	1.52 (0.55–4.16)	NS
Shetty²⁹	1999	Case control	328	Any steroid use ＞6 mo	1.03 (1.00–1.06)	NS
Eaden³⁰	2000	Case control	204	Regular steroid use vs. none	0.26 (0.01–0.70)	0.008
van Staa³¹	2005	Population based case control	700	Any steroid use in the last 6 mo	1.83 (1.17–2.88)	＜0.05
Velayos²¹	2006	Case control	376	Steroid use ＞1 yr	0.4 (0.2–0.8)	＜0.05
Siegel²⁰	2006	Case control	54	Any steroid use vs. none	0.56 (0.15–1.85)	0.42
Gupta²³	2007	Retrospective cohort	418	Steroid use ＞4 mo	0.6 (0.2–1.7)	NS
Terdiman²⁶	2007	Population based case control	1,536	Steroid use in the last 1 yr	1.43 (1.09–1.87)	＜0.05
Tang²⁴	2010	Case control	48	Ever used steroids vs. none	1.0 (0.17–6.29)	1.00

Table 3.

Studies Evaluating the Role of Immunomodulators in Prevention of Dysplasia/Colorectal Cancer in Patients with Inflammatory Bowel Disease

First author	Year	Design P	Patient (n)	Agent	OR/RR (95% CI)	p-value
Connell¹¹	1994	Case control	266	Azathioprine ever use vs. none	0.38 (0.02–4.26)	0.54
Lashner¹⁰	1997	Retrospective cohort	98	Azathioprine use ＞6 mo	1.12 (0.26–4.77)	NS
Fraser³²	2002	Retrospective cohort	1,349	Azathioprine (yes vs. no)	0.8 (0.33–1.85)	NS
Rutter³³	2004	Case control	204	Azathioprine ＞1 yr	0.22 (0.03–1.87)	0.17
van Staa³¹	2005	Population based case control	700	Thiopurine use in the last 6 mo	0.85 (0.25–2.94)	NS
Matula³⁴	2005	Retrospective cohort study	315	Thiopurine use ＞3 mo	1.06 (0.59–1.93)	NS
Velayos²¹	2006	Case control	376	Thiopurine use ＞1 yr	3.0 (0.7–13.6)	NS
Siegel²⁰	2006	Case control	54	Any immunomodulator ever vs. none	0.57 (0.12–2.25)	0.51
Gupta²³	2007	Retrospective cohort	418	Thiopurine ＞4 mo	0.8 (0.3–2.7)	NS
Terdiman²⁶	2007	Population based case control	1,536	Immunomodulator use in the last 1 yr	1.35 (0.92–1.98)	NS
Tang²⁴	2010	Case control	48	6MP ever use vs. none	0.38 (0.02–4.26)	0.45
Baars²⁷	2011	Population based case control	566	Thiopurine use ever vs. none	0.36 (0.16–00.56)	＜0.05
van Schaik²⁸	2012	Population based cohort (registry)	2,578	Azathioprine ＞50 mg for 6 mo	0.10 (0.01–0.75)	＜0.05

Table 4.

Studies on the Chemopreventive Effect of Folic Acid Supplementation on Dysplasia or Colon Cancer Risk in Patients with Inflammatory Bowel Disease

First author	Year	Design	Patient (n)	Agent	OR/RR (95% CI)	p-value
Studies with folic acid supplementation as primary interest
Lashner¹²	1989	Case control	99	Folic acid (yes vs. no)	0.38 (0.12–1.20)	NS
Lashner¹⁰	1997	Retrospective	98	Folic acid 0.4 mg ＞6 mo	0.76 (0.36–1.61)	NS
		Cohort study		Folic acid 1 mg ＞6 mo	0.54 (0.20–1.48)	NS
Studies where folic acid supplementation was a secondary interest
Shetty²⁹	1999	Case control	328	Folic acid (use ＞6 mo)	0.47 (0.18–1.20)	NS
Rutter³³	2004	Case control	204	Folic acid (yes vs. no)	0.4 (0.05–3.42)	0.4
Velayos²¹	2006	Case control	336	Folic acid (use noted on 2 of office visits)	0.9 (0.4–1.8)	NS
Siegel²⁰	2006	Case control	54	Folic acid (yes vs. no)	0.80 (0.16–3.72)	1.00
Gupta²³	2007	Retrospective cohort	418	Folic acid (use ＞4 mo)	1.3 (0.4–3.7)	NS
Tang²⁴	2010	Case control	48	Folic acid (1 mg/day)	0.11 (0.06–0.79)	0.002
Baars²⁷	2011	Population based case control	566	Folic acid (yes vs. no)	0.93 (0.51–1.71)	NS
van Schaik²⁸	2012	Population based cohort study	2,578	Folic acid (yes vs. no)	2.11 (0.45–9.94)	NS
Song⁵¹	2012	Case control	5,442	Folic acid (yes vs. no)	1.01	0.97

Table 5.

Studies Evaluating the Role of NSAIDs, Aspirin and Statins in Prevention of Dysplasia/Colorectal Cancer in Patients with Inflammatory Bowel Disease

First author	Year	Design	Patient (n)	Agent	OR/RR (95% CI)	p-value
NSAIDS
Bansal⁵⁸	1996	Retrospective cohort	11,446	Having an NSAID related diagnosis	0.84 (0.65–1.09)	NS
van Staa³¹	2005	Population based case control	700	Any NSAID use in the last 6 mo	0.80 (0.38–1.66)	NS
Velayos²¹	2006	Case control	376	NSAID use noted on 2 office visits	0.1 (0.03–0.5)	＜0.05
Terdiman²⁶	2007	Population based case control	1,536	NSAID use in the last 1 yr	0.97 (0.74–1.28)	NS
Tang²⁴	2010	Case control	48	Ever used NSAID vs. none	0.29 (0.17–3.07)	0.36
Baars²⁷	2011	Population based case control	376	Ever used NSAID vs. none	1.96 (0.72–5.36)	NS
Samadder⁵⁹	2011	Population based case control	60	NSAID use once weekly for at least 3 yr	0.47 (0.12–1.86)	NS
Broughton⁶⁰	2012	Case control	23	NSAID use (yes vs. no)	0.54 (0.20–1.35)	0.19
Aspirin
Eaden³⁰	2000	Case control	204	Aspirin use (yes vs. no)	0.80 (0.21–2.98)	0.74
van Staa³¹	2005	Population based case control	700	Aspirin use in the last 6 mo (prescribed only)	1.52 (0.70–3.28)	NS
Velayos²¹	2006	Case control	376	Aspirin use noted on 2 office visits (self-reported)	0.3 (0.1–0.8)	＜0.05
Broughton⁶⁰	2012	Case control	58	Aspirin use (yes vs. no)	0.36 (0.18–0.70)	＜0.01
Statin
Poynter⁶¹	2005	Case control	55	Statin use for at least 5 yr	0.06 (0.006–0.55)	＜0.05
Samadder⁵⁹	2011	Case control	60	Statin use for at least 5 yr	0.07 (0.01–0.78)	＜0.05
Broughton⁶⁰	2012	Case control	233	Statin ＜40 mg/day	0.51 (0.21–1.24)	0.14
				Statin ≥40 mg/day	0.19 (0.07–0.47)	＜0.01
				Duration ＜2 yr	0.66 (0.21–1.69)	0.47
				Duration 2–5 yr	0.38 (0.14–1.01)	0.05
				Duration ＞5 yr	0.18 (0.06–0.55)	＜0.01

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