Irritable bowel syndrome and colon cancer: A meta-analysis

Table 1 Characteristics of the included studies, mean ± SD

Ref.	Age	CRC diagnosis	IBS diagnosis	Population description	Number of participants	Study design	Country
Akhtar et al[14], 2006	Range 19-91	Biopsy	Rome I/II, Manning criteria	Not clearly specified	169 cases, 186, and controls	Cross-sectional	United States
Canavan et al[15], 2014	42.9	GP diagnosis	GP diagnosis	Inclusion: Age 18-75; exclusion: CD, IBD, CRC	112854 cases, and 546903	Cohort	United Kingdom
Chang et al[10], 2015	60.9 ± 12.2	IFOBT, colonoscopy, and national cancer registry	ICD-9: 564.0, 564.1	Excluded patients with a colonic neoplasia or IBS diagnosis before screening	91160 cases, and 39224 controls	Cohort	Taiwan
Chey et al[16], 2010	41.1 ± 12.9	NA	Rome II criteria	Excluded IBS-C, alarm features, pregnancy, family history of CRC, prior GI disease/surgery	466 cases, and 451 controls	Cross-sectional	United States
Gu et al[17], 2011	34.1 ± 7.8	Biopsy	Rome III criteria	Excluded alarm features, family history of CRC, onset > 50 years	3332 cases, and 1588 controls	Cross-sectional	China
Ejtehadi et al[5], 2023	37.8 ± 12.4	Biopsy	Rome IV criteria	IBS patients undergoing colonoscopy compared with controls	96 IBS patients, and 101 controls	Comparative cross-sectional	Iran
Hsiao et al[11], 2014	44.6 ± 19.7	ICD-9: 153, 154	ICD-9: 564.1	Excluded cancer and missing demographic data	527077 cases, and 1014793 controls	Cohort	Taiwan
Ishihara et al[18], 2012	Median 57.9	Biopsy	Rome III criteria	Excluded emergency cases with melena	198 cases, and 3831 controls	Cross-sectional	China
Staller et al[19], 2021	44.7 ± 17.0	SNOMED	ICD-9: 564B; ICD-10: K58	Colonoscopy with biopsy < 6 months from IBS diagnosis; exclusion of CD, MC, CRP, CRC	21778 cases, and 1679334 controls	Cross-sectional	Sweden

CRC: Colorectal cancer; IBS: Irritable bowel syndrome; GP: General practitioner; IFOBT: Immunochemical fecal occult blood test; NA: Not available; ICD: International Classification of Diseases; SNOMED: Systematized nomenclature of medicine; CD: Crohn’s disease; IBS-C: Irritable bowel syndrome with constipation; GI: Gastrointestinal; MC: Microscopic colitis; CRP: C-reactive protein.

Table 2 Newcastle Ottawa Scale risk of bias of the included studies

Ref.	Selection (4)	Comparability (2)	Outcome (3)	Total score	Quality
Akhtar et al[14], 2006	2	1	2	5/9	Low
Canavan et al[15], 2014	3	2	3	8/9	High
Chang et al[10], 2015	4	2	2	8/9	High
Chey et al[16], 2010	3	1	2	6/9	Moderate
Gu et al[17], 2011	3	1	2	6/9	Moderate
Ejtehadi et al[5], 2023	3	1	2	6/9	Moderate
Hsiao et al[11], 2014	4	2	2	8/9	High
Ishihara et al[18], 2012	3	1	1	5/9	Moderate
Staller et al[19], 2021	3	1	1	5/9	Moderate

Table 3 Certainty (grading of recommendations assessment, development, and evaluation) of evidence of the outcomes

Outcome	Number of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other consideration	Certainty of evidence
IBS and CRC	6	6 cross-sectional	Not serious	Serious (I2 = 79%)	Not serious	Serious	None	Very low
IBS and CRC	3	Three retrospective	Not serious	Serious (I2 = 99%)	Not serious	Serious	None	Very low
IBS and CRC, removing outliers	5	Four cross-sectional and 1 cohort	Not serious	Not serious (I2 = 0%)	Not serious	Not serious	None	Low

CRC: Colorectal cancer; IBS: Irritable bowel syndrome.

Table 4 Irritable bowel syndrome diagnostic criteria (Rome I vs II vs III vs IV)

Feature	Rome I (1990)	Rome II (1999)	Rome III (2006)	Rome IV (2016)
Core symptom	Abdominal pain relieved with defecation or associated with stool change	Abdominal pain or discomfort	Recurrent abdominal pain or discomfort	Recurrent abdominal pain only (discomfort removed)
Minimum duration	≥ 3 months	≥ 12 weeks in past 12 months	≥ 3 days/month in last 3 months	≥ 1 day/week in last 3 months
Symptom onset before diagnosis	Not clearly defined	Not clearly defined	≥ 6 months before diagnosis	≥ 6 months before diagnosis
Required associated features (≥ 2)	Relief with defecation	Relief with defecation	Related to defecation	Related to defecation
	Change in stool frequency	Change in stool frequency	Change in stool frequency	Change in stool frequency
	Change in stool form	Change in stool form	Change in stool form	Change in stool form
Discomfort allowed?	Yes	Yes	Yes	No
Subtypes defined	Not standardized	Emerging stool-based	IBS-constipation, IBS-diarrhea, IBS-mixed, IBS-U (Bristol scale)	Same subtypes, stricter stool frequency thresholds
Diagnostic strictness	Least strict	More structured	Moderate	Most strict

IBS: Irritable bowel syndrome.