Irritable bowel syndrome and colon cancer: A meta-analysis

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that negatively affects quality of life and psychological well-being. Because IBS is diagnosed using symptom-based criteria such as the Rome criteria, its clinical manifestations may overlap with those of colon cancer, raising concerns about potential misdiagnosis.

AIM

To evaluate the association between IBS and colon cancer.

METHODS

A systematic search of PubMed/MEDLINE, Web of Science, and Google Scholar was conducted for English-language articles published up to January 2026. The search was performed between December 2025 and January 2026 using the keywords “irritable bowel syndrome”, “colon cancer”, “colorectal cancer”, “rectosigmoid cancer”, and “gastrointestinal cancer”, combined with the Boolean operators “AND” and “OR”. Through this, a total of 1013 records were identified. After removing duplicates, 469 articles remained; of those remaining articles, 79 full-text articles were screened for eligibility and 9 studies were included in the final meta-analysis.

RESULTS

The pooled analysis showed no significant association between IBS and colon cancer compared with controls [odds ratio (OR) = 1.05, 95%CI: 0.57-1.94]. Sensitivity analysis after removal of outliers yielded similar results (OR = 1.25, 95%CI: 0.86-1.81). Furthermore, 3 longitudinal studies demonstrated no association between IBS and colon cancer (risk ratio = 1.00, 95%CI: 1.00-1.00).

CONCLUSION

Overall, the findings indicate that IBS is not associated with an increased risk of colon cancer. These results support adherence to current guideline-based diagnostic criteria for IBS while maintaining appropriate clinical vigilance for alarm features suggestive of malignancy.

Key Words: Irritable bowel syndrome; Colon cancer; Colorectal cancer; Rome criteria; Misdiagnosis; Cancer risk; Functional bowel disorders

Core Tip: Irritable bowel syndrome (IBS) is prevalent, and this prevalence varies depending on geography, diagnostic methods, and sociodemographic factors. The Rome criteria are the most commonly used diagnostic method, however, an important limitation of the Rome criteria overall is their potential overlap with organic diseases. This can complicate diagnosis and increase the risk of missing significant organic pathology if careful clinical evaluation is not performed. There is a recent concern regarding the association between IBS and colorectal cancer (CRC), particularly in those < 50 years of age. The current review synthesized the most recent evidence regarding the association between CRC and IBS.

INTRODUCTION

Irritable bowel syndrome (IBS) is not uncommon; its prevalence varies significantly depending on the diagnostic criteria, geography, and culture. The reported prevalence is 10.1% and 3.8% when using Rome III and Rome IV, respectively. In the United States, the prevalence varies from 7% to 16% with young women more affected[1,2]. Importantly, the change in the dynasty of symptoms along with the suggestion by the Rome IV criteria to include the gut-brain interaction, and the overlap with other functional gastrointestinal syndromes has encouraged research in this field[3,4]. It is vital to explicitly exclude patients presenting with alarm features such as unintentional weight loss, rectal bleeding, or recent changes in bowel habits. IBS is primarily diagnosed using symptom-based criteria; however, diagnostic accuracy can be improved through comprehensive clinical evaluation. This includes obtaining a detailed medical history with particular attention to somatoform and psychological comorbidities[5]. A thorough physical examination, including digital rectal examination, is essential. Additionally, limited laboratory screening, specifically the assessment of hemoglobin levels and C-reactive protein concentrations, is recommended to exclude underlying organic pathology[6].

Due to its chronic nature, mental IBS significantly impacts the patient’s quality of life due to its organic and psychological effects. In addition, the issue of IBS is dynamic, and the understanding of the syndrome is rapidly changing due to recent advances in relevant clinical research[7]. The diagnosis of IBS is based mainly on the Rome criteria, which are subjective. The Rome IV criteria are more stringent and may fail to classify milder forms of IBS as functional disorders. Therefore, they are particularly valuable in tertiary care centers, where diagnostic precision is critical, and the risk of misdiagnosing serious conditions such as colon cancer must be minimized. In contrast, the Rome III criteria were broader and more likely to capture milder or ambiguous symptom presentations[8,9].

However, an important limitation of the Rome criteria overall is their potential overlap with organic diseases. Symptoms attributed to functional bowel disorders may also occur in conditions such as inflammatory bowel disease and other chronic overlapping pain conditions, which can complicate diagnosis and increase the risk of missing significant organic pathology if careful clinical evaluation is not performed[10].

Colon cancer burden is high-it is listed as the third most common cancer worldwide. The global prevalence of colon cancer significantly increased from 4.27 million in 2016 to 11.68 million cases in 2021. Importantly, the mortality increased by 139.4%. The rising incidence of colorectal cancer (CRC) among younger populations highlights the urgent need for adapting the Rome criteria to minimize the risk of overlooking significant conditions, including colon cancer[11,12]. Therefore, assessing the overlap of IBS with colon cancer is justifiable to improve the subjective Rome criteria. This review aims to discuss the overlap between IBS and colon cancer.

MATERIALS AND METHODS

This meta-analysis was conducted during December 2025 and January 2026 and followed the PRISMA guidelines. This meta-analysis was not registered in PROSPERO because the majority of the included studies were observational (Figure 1).

Figure 1 The association between irritable bowel syndrome and colorectal cancer literature search (the PRISMA chart).

Included studies

We included prospective and retrospective cohorts, cross-sectional, and case-control studies evaluating the association of CRC and IBS.

Exclusion criteria

Case reports, case series, editorials, opinions, systematic reviews, meta-analyses, and study protocols without results were excluded. Studies not reporting the association of IBS and CRC were also excluded.

Outcomes measures

The outcome measure was the association of IBS with colorectal malignancy.

Literature search

Two authors independently searched PubMed, Web of Science, and Google Scholar for studies evaluating the association between IBS and colorectal malignancy. The search was conducted in November and December 2025 and January 2026. All English-language articles published from database inception to January 30, 2026, were considered. The keywords used included “IBS”, “irritable bowel syndrome”, “colon cancer”, “colorectal malignancy”, “rectosigmoid cancer”, and “gastrointestinal cancer”, combined using the Boolean operators “AND” and “OR”. A total of 1013 records were identified, of which 469 remained after removal of duplicates. From those, 79 full-text articles were screened, and 9 studies were included in the final meta-analysis (Supplementary Table 1).

Data extraction

The first author’s name, country, year of publication, age of patients, study duration, number of participants in IBS and controls, CRC in IBS and controls were exported to an Excel sheet (Table 1)[13-19].

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.

The quality of the included studies’ assessment

We used the Newcastle Ottawa Assessment Tools[13] (Table 2).

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

The quality of evidence

Analysis of the quality of evidence by Grading of Recommendations Assessment, Development, and Evaluation[14] (Table 3).

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.

Statistical analysis

Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, United Kingdom) was used for the data analyses. For IBS with colorectal malignancy, forest plots were used to visualize and summarize the data. All the data were dichotomous, and the odds ratio (OR) was used in the cross-sectional studies. However, in 3 studies reporting longitudinal follow-up with incident CRC outcomes, the pooled effect is more appropriately expressed as a risk ratio (RR), which accounts for time-to-event data and varying follow-up duration; for rare outcomes in large cohorts, the pooled RR closely approximates the hazard ratio (HR). A random effects meta-analysis was used to pool studies with similar characteristics, particularly when significant heterogeneity existed, and 95%CIs were calculated to quantify the precision of the pooled effect estimate. The I² statistic was used to evaluate the degree of heterogeneity among studies. An I² value < 25% was considered low heterogeneity, whereas a value > 50% indicated substantial heterogeneity. We generated funnel plots to assess potential publication bias in the meta-analysis of the included studies. A subgroup analysis was conducted to identify the source of heterogeneity after removing the outlier studies contributing most to the heterogeneity. A P value < 0.05 was considered statistically significant.

RESULTS

Characteristics of the included studies

A total of 9 studies[5,10,11,14-19] were included in the analysis. Of these, 2 were conducted in Europe, 2 in the United States, and 5 in Asia. The included studies comprised 6 with a cross-sectional design and 3 with a retrospective design. The age of participants ranged from 19 to 90 years. The majority of CRC diagnoses were confirmed by biopsy. In contrast, the diagnosis of IBS varied considerably across studies, with Rome I, Rome II, Rome III, and Rome IV criteria being used. Table 4. The quality was moderate in 5 studies, high in 3 studies, and low in 1 study (Tables 1 and 2)

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.

The association between CRC and IBS in cross-sectional studies using the OR

In this meta-analysis, IBS is not associated with CRC compared to controls after pooling 6 cross-sectional studies, OR = 1.05, 95%CI: 0.57-1.94; Z = 0.15; P = 0.88). Substantial heterogeneity was observed (I² = 79%, χ² = 23.73, df = 5, P = 0.0002; τ² = 0.38) (Figure 2A). The results were unchanged after subgroup sensitivity analysis (removing outliers), with no significant association between IBS and CRC (OR = 1.25, 95%CI: 0.86-1.81; Z = 1.18; P = 0.24). No heterogeneity was detected (I² = 0%, χ² = 3.93, df = 4, P = 0.75) (Figure 2B).

Figure 2 The conditions of patients with irritable bowel syndrome and the control group. A: Colorectal cancer (CRC) in irritable bowel syndrome (IBS) and control subjects; B: CRC in IBS and control subjects (no heterogeneity). IBS: Irritable bowel syndrome.

The association between CRC and IBS in cohort studies using the RR

Across 3 population-based cohort studies, a total of 2323011 participants were included (731091 with IBS and 1591920 controls). Using a random-effects model, IBS was not associated with an increased risk of CRC (RR = 1.00, 95%CI: 1.00-1.00; Z = 0.04; P = 0.97). Considerable heterogeneity was observed across studies (I² = 99%, χ² = 362.18, df = 2, P < 0.00001; τ² = 0.00) (Figure 3).

Figure 3 Colorectal cancer in irritable bowel syndrome and control subjects, risk ratios. IBS: Irritable bowel syndrome.

DISCUSSION

In this meta-analysis, IBS is not associated with CRC compared to controls, with an OR of 1.05, 95%CI: 0.57-1.94. The results were not changed after a subgroup sensitivity analysis (removing outliers), OR = 1.25, 95%CI: 0.86-1.81. There was no association between CRC and IBS in 3 longitudinal studies after using the HR, RR = 1.00, 95%CI: 1.00-1.00. The current findings supported Vichos et al[20], who found no association between IBS and CRC (OR = 0.40, 95%CI: 0.09-1.77). However, the authors included only 6 studies. In addition, their findings were limited by the high heterogeneity. Wu et al[6] conducted a meta-analysis and found a slightly higher CRC in IBS in the short-term, with no increased risk in the long-term. Importantly, the authors included only 5 studies that evaluated the CRC OR.

IBS is a major health burden and affects 7%-16% of the general population. Despite its high prevalence, the diagnosis remains primarily symptom-based rather than reliant on structural abnormalities. Consensus supports a more pragmatic clinical approach that focuses on the key symptom triad of recurrent abdominal pain, bowel dysfunction (diarrhea, constipation, or mixed patterns), and abdominal bloating[6]. Physical examination, including digital rectal examination, is recommended. Limited but targeted laboratory investigations, particularly hemoglobin and C-reactive protein measurements, are recommended to help exclude underlying organic disease, allowing clinicians to confidently establish a positive diagnosis of IBS without extensive and unnecessary testing[21]. A positive diagnostic approach is vital to avoid the patients’ anxiety and concerns that they may be affected by organic disorders and CRC. The current recommendations are against the diagnosis by exclusion[22].

The current findings differ from those of Wu et al[6], who suggested a slightly higher incidence of CRC following a diagnosis of IBS. In those studies, the observed increase in CRC among patients with IBS compared with non-IBS controls should be interpreted cautiously, as the data did not establish a causal relationship. Because CRC typically develops over a long latency period, a true etiological link would be expected to manifest as a progressively increasing risk with longer follow-up. However, the excess risk reported in the Wu et al’s study[6] was largely confined to the first year after the initial IBS diagnosis. This temporal pattern suggests that the apparent association may be explained by diagnostic misclassification rather than a biological effect[23,24]. It’s worth noting that big studies looking at lots of people have found that the higher number of colon cancer cases seen soon after someone is diagnosed with IBS is probably because the symptoms of the 2 conditions are similar, not because one actually causes the other. In the long run, people with IBS don’t seem to have a higher risk of getting colon cancer; their risk might even be lower[25]. IBS and CRC share several nonspecific gastrointestinal symptoms, which may lead to early CRC cases being initially misdiagnosed as IBS, especially when the malignancy is still mild or nonspecific in presentation. In contrast, our analysis did not demonstrate a significant association between IBS and CRC, supporting the interpretation that previously reported early increases in CRC incidence among IBS patients may largely reflect misclassification at the time of initial diagnosis rather than a true increase in cancer risk[26]. Our findings supported the Rome IV criteria that colonoscopy should be conducted in patients > 50 years with anemia, rectal bleeding suggestive of malignancy, unintentional weight loss, fever, abdominal masses, and lymph nodes enlargement[27].

CRC diagnosed at a younger age has become an important focus of recent research[28,29]. There is evidence that early-onset CRC cases are steadily increasing. Importantly, a longer interval is present between the onset of symptoms and definitive diagnosis. As a result, young patients with CRC are more frequently identified at more advanced stages of disease compared with older patients[30,31]. Given that CRC typically develops gradually over many years, effective screening programs have the potential to detect precancerous lesions or early malignancy before progression to advanced, less treatable stages. Early detection can therefore lower disease incidence, reduce mortality, and improve survival outcomes. In response to these trends, several investigations have evaluated whether CRC screening should begin earlier in life. Reflecting this evidence, the American Cancer Society now recommends that average-risk adults initiate CRC screening at 45 years of age rather than the previous threshold of 50 years[32-36]. The main screening methods include colonoscopy, fecal occult blood testing, fecal immunochemical testing, and stool DNA testing[25,37].

Strengths and limitations

The strength of this meta-analysis is that it included the largest up-to-date studies compared to the previous meta-analysis. In addition, we conducted a sensitivity analysis and showed that the results were not different. However, the high heterogeneity due to the inclusion of studies with different methodologies significantly limited this study.

CONCLUSION

In this meta-analysis, IBS is not associated with CRC compared to controls. Physicians need to adhere to the current guidelines for the diagnosis and treatment of IBS.

ACKNOWLEDGEMENTS

We would like to acknowledge Dr. Ihab Farah, Faculty of Science, University of Tabuk, Saudi Arabia, for the Statistical analysis, and Mohannad Osman, Fahd Bin Sultan University, Tabuk, Saudi Arabia, for recording the core tip.