Increased risk of colorectal adenoma and benign colorectal polyp associated with Helicobacter pylori infection: a systematic review and meta-analysis
Original Article

Increased risk of colorectal adenoma and benign colorectal polyp associated with Helicobacter pylori infection: a systematic review and meta-analysis

Ju Hee Kim1,2,3# ORCID logo, Hyun Wook Han1,2,3,4# ORCID logo, Joo Hye Song5 ORCID logo, Seong-Jang Kim6,7 ORCID logo, Young Kook Kim8,9 ORCID logo, Hye Jun Kim1,2,3 ORCID logo, Taeho Greg Rhee10,11,12 ORCID logo, Sung Ryul Shim13,14 ORCID logo

1Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Republic of Korea; 2Institute for Biomedical Informatics, School of Medicine, CHA University, Seongnam, Republic of Korea; 3Institute of Basic Medical Sciences, School of Medicine, CHA University, Seongnam, Republic of Korea; 4Healthcare Big-Data Center, Bundang CHA Hospital, Seongnam, Republic of Korea; 5Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea; 6Department of Nuclear Medicine, College of Medicine, Pusan National University, Yangsan, Republic of Korea; 7BioMedical Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; 8Department of Ophthalmology, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 9EyeLight Data Science Laboratory, Seoul, Republic of Korea; 10Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA; 11Mental Illness, Research, Education and Clinical Center (MIRECC) of New England, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA; 12Department of Public Health Sciences, School of Medicine, University of Connecticut, Farmington, CT, USA; 13Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea; 14Konyang Medical data Research group-KYMERA, Konyang University Hospital, Daejeon, Republic of Korea

Contributions: (I) Conception and design: SR Shim, HW Han; (II) Administrative support: SR Shim; (III) Provision of study materials or patients: SR Shim, JH Song, HJ Kim, JH Kim; (IV) Collection and assembly of data: SR Shim, JH Song, SJ Kim, JH Kim; (V) Data analysis and interpretation: SR Shim, JH Kim, SJ Kim, YK Kim, TG Rhee, HW Han; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Correspondence to: Sung Ryul Shim, MPH, PhD. Department of Biomedical Informatics, College of Medicine, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea; Konyang Medical data Research group-KYMERA, Konyang University Hospital, Daejeon, Republic of Korea. Email: sungryul.shim@gmail.com.

Background: Although the association between Helicobacter pylori (H. pylori) infection and the risk of colorectal adenomas (CRAs) is suggested, specific analysis of the histological subtype of CRA is limited. The aim of the study was to conduct a meta-analysis on the risk of histological classifications of CRA as benign colorectal polyp (BCP), CRA, and advanced CRA to investigate the effects of H. pylori.

Methods: A comprehensive literature searches of the PubMed, Embase, and Cochrane databases through January 2024. Meta-regression analysis was conducted to identify potential moderators (e.g., histological subtype and ethnic groups).

Results: Among the 503,365 participants across 40 studies, H. pylori was consistently associated with increased probabilities of BCP, CRA, and advanced CRA. In BCP, H. pylori positive was found to be associated with an increase [odds ratio (OR), 1.430; 95% confidence interval (CI): 1.292–1.583]. In CRA and advanced CRA, H. pylori positive was found to be associated with an increase (OR, 1.711; 95% CI: 1.408–2.080). In subgroup analysis by ethnicity, Western group had lower OR compared to Asian, with a statistically significant difference observed (Western OR, 1.369; 95% CI: 1.222–1.535 vs. Asian OR, 1.990; 95% CI: 1.416–2.796, P=0.04).

Conclusions: This systematic review and meta-analysis findings revealed a significant association between H. pylori infection and BCP, CRA, and advanced CRA. In particular, meta-regression analysis confirmed that ethnicity acts as a risk factor in both BCP and CRA.

Keywords: Helicobacter pylori (H. pylori); colorectal adenoma (CRA); colorectal polyp; meta-analysis; systematic review


Submitted May 14, 2024. Accepted for publication Jan 27, 2025. Published online Apr 07, 2025.

doi: 10.21037/tcr-24-795


Highlight box

Key findings

• In this systematic review and meta-analysis, we identified all reported risks for colorectal adenomas (CRAs) associated with Helicobacter pylori (H. pylori) infection.

What is known and what is new?

• The effects of sociodemographic covariates as well as moderators such as ethnicity, polyp type, and qualitative analysis of individual studies well recognized.

• This study findings revealed a significant association between H. pylori infection and benign colorectal polyp, CRAs, and advanced CRAs.

What is the implication, and what should change now?

• Our findings allow experts to assess the overall risk of CRAs following H. pylori infection by considering various covariates.


Introduction

Helicobacter pylori (H. pylori) is a predominant microorganism primarily inhabiting the stomach, and its infection is strongly linked to the development of gastrointestinal diseases such as gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma (1). Afflicted individuals typically manifest chronic gastric inflammation and an immune-mediated inflammatory reaction towards host gastric cells, culminating in heightened gastrin secretion (2). Numerous studies on H. pylori have been conducted to elucidate the pathogenesis of upper gastrointestinal disorders, revealing its association not only with digestive tract diseases but also with systemic disorders extending beyond the stomach (3,4). Given the conceivable link between upper gastrointestinal disorders and the onset of colorectal neoplasms, scholars have long endeavored to probe the potential correlation between H. pylori infection and colorectal cancer (CRC) (5,6).

CRC ranks as the third most prevalent cancer-related causes of death globally (7). Despite sustained scholarly inquiry into diverse factors encompassing dietary habits, lifestyle adjustments, environmental pollutants, and pharmaceutical agents, the pathogenesis remains intricate and only partially elucidated. Additionally, recent research indicates that the incidence rate of CRC, traditionally acknowledged as highest among middle-aged and older adults, has exceeded that of the elderly population. Based on current findings the incidence rate of CRC, measured through annual percentage change, has demonstrated a more pronounced increase in the 10–40-year age group (1.6%) compared to the 50–74-year age group (0.6%) (8). The most potent preventive measure identified thus far is prior colonoscopy screening (9,10). Colorectal adenomas (CRAs) identified during such screenings manifest a broad array of cancer-related molecular alterations, with histological, morphological, and genetic changes occurring progressively through a stepwise process (11). Previous studies have implicated the association between CRA detected during colonoscopy and H. pylori infection (12,13).

Numerous meta-analyses have suggested an association between H. pylori infection and an increased risk of CRC; however, there is limited specific analysis regarding the varying associations based on the histological subtypes of colon polyps (14). The progression to cancer is not sudden; rather, colon polyps persist as benign growths over an extended period before transitioning to malignancy (15). Thus, investigating the impact of H. pylori infection at varying stages of polyps is imperative. The aim of our study was to conduct a meta-analysis to assess the impact of H. pylori infection on colon polyps according to their histological classification as benign colorectal polyp (BCP), CRA, and advanced CRA. We present this article in accordance with the MOOSE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-795/rc).


Methods

This systematic review and meta-analysis was registered at PROSPERO (CRD42022308533).

Search strategy

For this study, we collected literature rigorously from PubMed, Embase, and Cochrane databases using Medical Subject Headings and text keywords through January 2024 (Table S1). The main key words and medical terms included those related to population of interest (i.e., individuals who received colonoscopy screening for BCP or CRA), exposure (H. pylori infection positive), and outcomes of interest (CRAs). The main key words were categorized using the Boolean operators. The study was not limited by language or study design. Two independent researchers (J.H.K. and S.R.S.) checked the clinical research registries and reference lists for additional studies to increase the completeness of the study.

Study selection

The study inclusion criteria were as follows: (I) the study population comprised patients who were diagnosed with colonic polyp after colonoscopy including BCP, CRA and advanced CRA, but excluded those diagnosed with cancer and carcinoma. Hyperplastic polyp and traditional serrated adenoma are classified as BCP, and sessile serrated adenoma, tubular adenoma, villous adenoma, non-advanced adenomatous polyp, adenomatous are classified as CRA. In the hyperplastic polyp and colorectal polyp, if there is no stage, it is defined as BCP, and if there is a stage notation, it is classified as CRA. Excluded from simple Juvenile polyposis adenoma and multiple colorectal polyps are excluded from adenoma unless there is a detailed stage. Sessile serrated adenoma is classified as advanced CRA if dysplasia exists or CRA if not. Tubular adenoma is classified as advanced CRA or CRA if not. Advanced CRA was defined as one of the following features according to the current guideline: villous component, ≥10 mm in size, and high-grade dysplasia (16); (II) the exposure included the positive detection of H. pylori infection in stomach; (III) the comparison group was those with the negative detection of H. pylori; and (IV) outcomes were the risk for colonic polyp [odds ratios (ORs)]. Two independent authors (J.H.K. and S.R.S.) checked the titles and abstracts of individual studies to ensure that they met our inclusion and exclusion criteria. Only eligible studies were then strictly selected through full text checking, and a predefined form was used for data extraction. When the two authors’ perspectives had discrepancies, individual cases were rigorously discussed and resolved in a meeting of all researchers. Finally, the studies selected for this meta-analysis were selected through a full researchers’ meeting. To ensure the absence of overlapping data and to maintain the meta-integrity, analysis’s references and data for each included study were carefully cross-checked.

Statistical analysis

All variables had the same measurement units, and the outcomes were recorded using binary data with a frequency of improvement. To adequately analyze the overall effect sizes, ORs with their corresponding 95% confidence intervals (CIs) using a random-effects model were used. If individual studies had multiple or different follow-up periods, the longest was selected.

Cochran’s Q test and the I2 statistic were used to assess proportion of total heterogeneity due to within-and between-study variations. Each moderator was subjected to a meta-regression analysis. To analyze potential moderators (e.g., number of patients, ethnic groups, study designs, polyp types, testing methods for H. pylori infection, research periods, population sources, and quality assessments), we estimated the variance of the true effects using a restricted maximum likelihood (REML) estimator. A two-sided P value less than 0.05 was considered for statistical significance. R 4.1.3 software (R Foundation for Statistical Computing, Vienna, Austria) was used to conduct this analysis (17).

Assessment of methodological quality

To evaluate the quality of this study, we used the Newcastle-Ottawa Quality Assessment Scale (NOS), which is based on three main factors (18). The first is the proper selection of participants, the second is the use of appropriate statistical analysis methods to evaluate comparisons, and the third is the clarity of the outcome measures and the adequacy of the study process. Each criterion was given a star rating; a study could receive one star for each item in the selection and outcome categories, but two stars for comparability. A maximum of nine stars can be awarded for all parameters. According to specific conditions, the qualitative power of the evidence related to the evaluation of benefits and drawbacks was exhibited (18).

Assessment of potential publication bias

We measured publication bias using a funnel plot. A funnel plot is to check whether publication bias exists in the meta-analysis by displaying the number of samples and the risk as a figure, respectively. First of all, looking at the funnel plot, it was judged that there would be no publication bias if the effect sizes of the studies were evenly distributed from side to side. In addition, it was confirmed whether publication bias exists as a test to statistically test publication bias (the Begg and Mazumdar rank correlation test and Egger’s linear regression test).


Results

Study selection

The initial search identified a total of 153 articles from different electronic databases (PubMed, n=43; Cochrane, n=2; Embase, n=105) and Websites (n=3). Twenty studies were removed as duplicates because they were extracted from more than one database. At screening, 43 studies were removed because they were not relevant to the scope of the study, and 49 studies (no target diseases, n=15; cancer or carcinoma, n=16; no exposure of H. pylori, n=6; no outcome of interest, n=2; commentary and letter, n=5; and others, n=5) were excluded because they did not meet the study’s inclusion and exclusion criteria during data extraction. Finally, 40 studies (Table 1) were selected for inclusion in this systematic review and meta-analysis after a rigorous selection process (Figure 1).

Table 1

Characteristics of the included trials

Study Country/region Age, years (mean ± SD) Male (%) No. of participants Study period Study population Study design Testing for HP infection Disease
Abbass 2011 (2) USA 59.1 39.6 192 2008–2009 Hospital Cross-sectional RUT or histologic examination CRA
Akalin 2019 (19) Turkey 60.54±10.69 61.2 831 2014–2018 Hospital Case-control IgG anti-HP antibody Benign hyperplasia, CRA
Aydin 1999 (20) Turkey 49 41.2 267 1996–1997 Hospital Case-control IgG anti-HP antibody CRA
Bae 2009 (21) Korea 61.2±9.7 72.9 346 2005–2008 Hospital Case-control UBT, RUT, or histological examination Advanced CRA
Basmaci 2023 (22) Turkey NA 46.5 3,231 2015–2019 Hospital Case-control IgG anti-HP antibody Advanced CRA
Breuer-Katschinsk 1999 (23) Germany 62.2±9.1 62.2 196 1993–1996 Hospital-based Case-control IgG anti-HP antibody CRA
Brim 2014 (24) USA ≥60 44.0 1,256 2005–2009 Hospital Cross-sectional Histologic examination or IgG anti-HP antibody CRA
ChangxiChen 2019 (25) China 58.6±11.3 81.7 1,375 2013–2014 Community-based Cross-sectional UBT Benign hyperplasia
Dong 2019 (26) China 5,543 2012–2017 Hospital NA UBT CRA
Feng 2023 (27) China 48.3±12 58.3 7,700 2015–2021 Hospital Cross-sectional UBT Benign hyperplasia
Fujimori 2005 (28) Japan 61.1±9.7 74.4 669 1996–2003 Hospital Cross-sectional UBT, RUT, or histological examination CRA
Georgopoulos 2006 (29) Greece 64 53.8 156 2000–2001 Hospital Case-control IgG anti-HP antibody CRA
Hong 2012 (30) Korea 49.2 38.3 2,195 2010 Community-based Cross-sectional UBT or histologic examination CRA, advanced CRA
Hong 2020 (31) Taiwan 56.71 73.8 2,475 2006–2015 Hospital Case-control EGD CRA
Hu 2017 (32) Taiwan 53.29±0.31 68.1 2,475 2006–2015 Community-based Cross-sectional RUT CRA
Huang 2019 (33) China 50.10±8.29 86.8 493 2010–2014 Hospital Case-control UBT Benign hyperplasia
Inoue 2011 (34) Japan 49.9 478 1996–2004 Community-based Case-control IgG anti-HP antibody Advanced CRA
Jia 2023 (35) China NA 73.2 191 2020–2022 Hospital Case-control Immune-histochemical stain Advanced CRA
Kim 2017 (36) Korea 51.6±7.9 8,916 2002–2010 Community-based Cross-sectional IgG anti-HP antibody CRA
Kumar 2018 (37) USA 64±12 38.8 8,963 2006–2016 Hospital Cross-sectional Histologic examination CRA
Lee 2022 (38) Taiwan 50 50.0 20,129 2005–2007 National-based Cross-sectional UBT Benign hyperplasia
Liou 2006 (39) Taiwan 50.27±0.55 57.5 462 NA Hospital Cross-sectional UBT Advanced CRA
Meucci 1997 (40) Italy 62 56.3 156 1993–1994 Hospital Case-control IgG anti-HP antibody CRA
Mizuno 2005 (41) Japan 58.5±1.18 60.4 307 NA Hospital Cross-sectional IgG anti-HP antibody CRA
Mohamed 2020 (42) Sudan 47.1±19.8 52.3 69 2017 Hospital NA UBT Benign hyperplasia
Nam 2017 (43) Korea 35 0 4,466 2007–2009 Community-based Cross-sectional RUT CRA, advanced CRA
Nam 2013 (44) Korea 56.9±9.5 67.5 597 2004–2005 Community-based Cross-sectional IgG anti-HP antibody CRA, advanced CRA
Patel 2014 (45) USA 53.7±11.0 42.8 798 2009–2011 Hospital Cross-sectional Histologic examination CRA
Ren 2021 (46) China 62.57±6.24 55.5 733 NA Hospital NA UBT Benign hyperplasia
Selgrad 2014 (47) Germany 66.38±9.83 50.1 377 2008–2013 Hospital Cross-sectional IgG anti-HP antibody CRA
Shao-Hua 2023 (48) China 54.34±10.92 48.1 792 2021–2022 Hospital Case-control UBT Advanced CRA
Shen 2021 (49) China 63.18±10.10 71.6 301 2018–2019 Hospital Cross-sectional UBT Benign hyperplasia
Siddheshwar 2001 (50) UK 66 64.9 368 1997–1999 Hospital Case-control IgG anti-HP antibody CRA
Sonnenberg 2013 (51) USA 57.8 58.8 119,142 2008–2011 Community-based Cross-sectional Histologic examination Advanced CRA
Sonnenberg 2020 (6) USA 62.7 28.2 302,061 2008–2018 National-based Case-control Immune-histochemical stain CRA
Teimoorian 2018 (52) Iran ≥50 66.7 150 2015–2016 Hospital Case-control IgG anti-HP antibody CRA
Tongtawee 2016 (53) Thailand 23.5 0 303 2014–2015 Hospital Cross-sectional RUT or histologic examination CRA
Yan 2017 (54) China 53.17 81.1 1,641 2014–2016 Community-based Cross-sectional UBT Benign hyperplasia
Zhuang 2022 (55) China 55.01±12.20 57.2 1,622 2019–2021 Hospital Case-control UBT Advanced CRA
Zuniga 2015 (56) USA 62.6 52.8 943 2010–2012 Community-based Case-control RUT, stool antigen test, or culture CRA

Traditional serrated adenoma, non-advanced adenomatous polyp, adenomatous are classified as CRA; in the hyperplastic polyp and colorectal polyp, if there is no stage, it is excluded from adenoma, and if there is a stage notation, it is classified as CRA; excluded from simple Juvenile polyposis adenoma; multiple colorectal polyps are excluded from adenoma unless there is a detailed stage; sessile serrated adenoma is classified as advanced CRA if dysplasia exists or CRA if not; tubular adenoma is classified as advanced CRA or CRA if not. CRA, colorectal adenoma; EGD, esophagogastroduodenoscopy; HP, Helicobacter pylori; IgG, immunoglobulin G; NA, not available; RUT, rapid urease test; SD, standard deviation; UBT, urea breath test.

Figure 1 PRISMA flow diagram of study selection process.

The 40 studies ultimately selected for systematic review and meta-analysis included 503,365 patients, and detailed demographic characteristics of the individual studies are shown in the Table 1. All of the studies were conducted in global region, and the research period included 1 to 10 years. The range of the calendar years of study and sample sizes in the quantitative meta-analysis were from 1993 to 2022 and 69 to 302,061 patients, respectively. Fifteen studies (37.5%) included Caucasian patients only and 25 studies (62.5%) had both Asian and other racial/ethnic minority groups. Further, seventeen studies used (42.5%) a case-control design and 20 studies (50.0%) used a cross-sectional design (Table 1).

Quality assessment

The quality assessment was conducted thoroughly using NOS by all authors. The authors strictly collected and evaluated each quality assessment domain. Thirty-two studies (80.0%) showed good quality, and the remaining eight studies (20.0%) had relatively small samples. It was judged that the confounding covariates were not properly controlled and evaluated as fair or poor (Table S2).

Outcomes

In CRA and advanced CRA, H. pylori positive was found to be associated with an increase (OR, 1.711; 95% CI: 1.408–2.080). Cochran’s Q test and Higgin’s I2 showed high heterogeneity (I2=90.0%). In subgroup analysis by ethnicity, Western group had lower OR compared to Asian, with a statistically significant difference observed (Western OR, 1.369; 95% CI: 1.222–1.535 vs. Asian OR, 1.990; 95% CI: 1.416–2.796, P=0.04) (Figure 2).

Figure 2 Forest plots. (A) Colorectal adenoma and advanced colorectal adenoma. (B) Benign hyperplasia. CI, confidence interval; IV, inverse variance; OR, odds ratio; SE, standard error.

In BCP, H. pylori positive was found to be associated with an increase (OR, 1.430; 95% CI: 1.292–1.583). Cochran’s Q test and Higgin’s I2 showed high heterogeneity (I2=80.0%) (Figure 2).

Effect size modifiers

The moderating effect of covariates using meta-regression analysis for each of BCP, CRA, and advanced CRA is shown in Table 2. The subgroup analysis was categorized according to sample size group (≥10,000 vs. <10,000), ethnic group (Western vs. Asian), study designs (case-control vs. cross-sectional), polyp types (CRA vs. advanced CRA), testing methods (invasive vs. non-invasive), research period (≥3 vs. <3 years), population source, and quality assessment criteria (poor & fair vs. good). Upon analyzing ethnic groups, H. pylori infection was found to be border line P value or significantly associated with an increased ORs at all stages among Asian compared to Western [BCP: Western OR, 1.26 (95% CI: 1.08–1.48), Asian OR, 1.52 (95% CI: 1.35–1.71), P=0.059; CRA and advanced CRA: Western OR, 1.37 (95% CI: 1.22–1.53), Asian OR, 1.99 (95% CI: 1.42–2.80), P=0.04]. When conducted using biopsy protocols as per the testing method, there was a significant association in promoting the detection of colorectal polyps in BCP [invasive method OR, 1.29 (95% CI: 1.17–1.42), non-invasive method OR, 1.58 (95% CI: 1.40–1.78), P=0.01]. In addition, the smaller the study period (P=0.03) were identified as risk factors in CRA and advanced CRA. However, in the subgroup analysis of polyp type, population source, and quality assessment, statistically significant differences in the association between H. pylori infection and the promotion of CRA were not found (Table 2).

Table 2

Effects of moderators for overall colorectal polyp risk

Variables CRA and advanced CRA Benign hyperplasia
k Odds ratio 95% CI P k Odds ratio 95% CI P
No. of total patients 0.06 0.23
   ≥10,000 3 1.29 1.01–1.66 3 1.33 1.21–1.47
   <10,000 34 1.78 1.43–2.18 10 1.49 1.28–1.72
Ethnic group 0.04 0.059
   Western 17 1.37 1.22–1.53 3 1.26 1.08–1.48
   Asian 20 1.99 1.42–2.80 10 1.52 1.35–1.71
Study design 0.40 <0.001
   Case-control 18 1.79 1.24–2.60 4 1.23 1.18–1.28
   Cross-sectional 19 1.52 1.37–1.69 9 1.52 1.36–1.69
Polyp type 0.20
   Colorectal adenoma 25 1.45 1.30–1.61
   Advanced colorectal adenoma 12 2.06 1.21–3.50
Test method for HP 0.57 0.01
   Invasive method 35 1.73 1.42–2.13 4 1.29 1.17–1.42
   Non-invasive method 2 1.32 0.53–3.29 9 1.58 1.40–1.78
Research period 0.03 0.29
   ≥3 years 18 1.41 1.27–1.56 5 1.33 1.10–1.60
   <3 years 19 2.13 1.48–3.07 8 1.50 1.32–1.71
Population source 0.24 0.93
   National 2 1.21 0.84–1.75 3 1.38 1.15–1.65
   Community 11 1.54 1.38–1.72 4 1.40 1.34–1.47
   Hospital 24 1.83 1.35–2.49 6 1.46 1.16–1.83
Quality assessment* 0.96
   Poor & fair 7 1.69 1.21–2.36
   Good 30 1.71 1.36–2.15

k, number of effect sizes; traditional serrated adenoma, non-advanced adenomatous polyp, adenomatous are classified as CRA; in the hyperplastic polyp and colorectal polyp, if there is no stage, it is excluded from adenoma, and if there is a stage notation, it is classified as CRA; excluded from simple Juvenile polyposis adenoma; multiple colorectal polyps are excluded from adenoma unless there is a detailed stage; sessile serrated adenoma is classified as advanced CRA if dysplasia exists or CRA if not; tubular adenoma is classified as advanced CRA or CRA if not; test methods for HP were divided into invasive (immune-histochemical stain, histologic examination, IgG anti-HP antibody, RUT) and non-invasive (UBT) methods; P value from meta-regression analysis using the restricted maximum likelihood. *, quality assessment follows Newcastle-Ottawa Quality Assessment. CI, confidence interval; CRA, colorectal adenoma; HP, Helicobacter pylori; RUT, rapid urease test; UBT, urea breath test.

Publication bias

The distribution of OR funnel plots appear to be symmetrical (Figure 3). The P values for the Begg and Mazumdar correlation test (P=0.14 of CRA and advanced CRA; P=0.90 of BCP) and Egger’s regression coefficient test (P=0.15 of CRA and advanced CRA; P=0.42 of BCP) in this meta-analysis indicate that there was no indication of publication bias or a small-study effect.

Figure 3 Funnel plots for publication bias. (A) Colorectal adenoma and advanced colorectal adenoma. (B) Benign hyperplasia.

Discussion

This systematic review and meta-analysis findings revealed a significant association between H. pylori infection and BCP, CRA, and advanced CRA. In particular, meta-regression analysis confirmed that ethnicity acts as a risk factor in both BCP and CRA.

Although most studies have focused on analyzing CRA stages that affect CRC among the various colon polyp types, our meta-analysis has been performed over a range of disease severity ranging from BCP, CRA, and advanced CRA associated with H. pylori infection. Furthermore, meta-regression analysis of various potential covariates (ethnicity, sample sizes, study designs, polyp types, test methods, technical, test methods, research period, population source, and quality assessment group) affecting risk was used to confirm whether they act as risk factors.

Previous research has consistently suggested a favorable correlation between H. pylori and CRA, particularly advanced CRA, supported by numerous significant findings (51,57), aligning with the outcomes of our meta-analysis. Hyperplastic polyps represent the most prevalent polypoid lesions encountered during colonoscopy (57). While lacking a notable association with CRC, their presence may signify a colonic microenvironment conducive to the genesis of sessile serrated polyps, whose increased size and multiplicity can heighten CRC risk (58,59). H. pylori infection fosters a positive relationship between diverse gastric histopathological abnormalities and the development of colonic polyps, attributed to diminished gastric acid barrier function and impaired gastric motility, which inhibit bacterial infiltration into the lower intestine (6). Moreover, prolonged suppression of gastric acid secretion may induce alterations in the bacterial composition of the lower gastrointestinal tract, potentially fostering the proliferation of colonic tumors (6). Additionally, chronic H. pylori infection may modulate the overall composition and responsiveness of the immune system to external stimuli (60). Our meta-analysis consistently revealed an association between H. pylori infection, spanning from BCP to CRA and advanced CRA.

In this study, it was confirmed that H. pylori infection in Asian increased the risk of BCP and CRA compared to Western. It is thought that this is probably the difference in the environment that makes up various diets and behaviors. For example, it has been suggested that H. pylori infection is associated with alterations and disparities in the gut microbial community, potentially induced through direct stimulation leading to hypergastrinemia (61-63). Moreover, the diversity of gut microbiota is subject to influence by a spectrum of environmental factors, notably including dietary parameters, which exert a notable influence (59). Previous studies analyzing the association between individual dietary patterns and overall gut bacteria uncovered no statistically significant distinctions in meal times or meal regularity between cohorts afflicted with CRC and control subjects. However, substantial disparities emerged concerning late-night snack consumption (64). Additionally, deleterious lifestyle habits such as nocturnal eating and prolonged wakefulness have been identified as risk factors for colorectal polyps (65). While consensus on whether H. pylori infection is independently associated with colorectal polyps and whether this association varies contingent on the histological subtype of colorectal polyps, the linkage between H. pylori and colorectal neoplasms is gaining traction. Our findings intimate that H. pylori infection exhibits associations commencing from the stage of BCP, with the significance of these associations amplifying concomitantly with the progression of polyp stages.

Although this study was the largest and most recent meta-analysis to date, some limitations in this study deserve comment. First, since this study is a systematic literature review and meta-analysis, it is assumed that individual studies are mixed without applying new pathological diagnostic criteria. For example, BCP is judged to have no malignant potential, but the possibility that BCP was significant in H. pylori cannot be excluded from the study results as new colon cancer pathways such as Sessile serrated adenoma is mixed. Therefore, readers should consider this in the interpretation of BCP. Second, significant heterogeneity has been confirmed in meta-analysis. This may inevitably be due to diverse research settings across the globe and/or methodological differences when synthesizing various studies. However, the validity of the results was tested using subgroup analyses or meta-regression analyses. And also, in some cases, there was a publication bias graphically; however, two publication bias tests to quantify the amount of bias captured by funnel plots reveal insignificant bias. Third, there were typical biases in observational studies. In CRA, the difference in risk according to the research period is indicated, which is presumed to be an overestimation bias commonly found in observational studies (66). In addition, the bias of these observational studies can also be confirmed in BCP, and the risk is higher when the test method is non-invasive, which is presumed to be an intended bias to increase sensitivity rather than specificity during diagnostic tests, and in the study design, it is estimated that these are general biases with a high risk of simple cross-sectional studies with a low-evidence level.


Conclusions

This systematic review and meta-analysis showed that there is a positive association between the H. pylori infection and CRA. In particular, special attention should be paid to some covariates, such as ethnicity, because they can act as risk factors. Further studies are still needed to establish a causal relationship between environmental factors or multifactorial causes and adenoma progression. In addition, prospective, long-term follow-up studies are needed for comprehensive and sufficient consideration.


Acknowledgments

None.


Footnote

Reporting Checklist: The authors have completed the MOOSE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-795/rc

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-795/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-795/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


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Cite this article as: Kim JH, Han HW, Song JH, Kim SJ, Kim YK, Kim HJ, Rhee TG, Shim SR. Increased risk of colorectal adenoma and benign colorectal polyp associated with Helicobacter pylori infection: a systematic review and meta-analysis. Transl Cancer Res 2025;14(4):2354-2366. doi: 10.21037/tcr-24-795

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