Occurrence and prognosis of metabolic dysfunction-associated steatosis liver disease and gastrointestinal tumors: a systematic review and meta-analysis

Abstract

Background

The metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common causes of chronic and abnormal liver function tests globally. The relationship between metabolic MASLD and gastrointestinal tumors (GI) remains controversial.

Methodology

We conducted a systematic review based on a protocol registered with PROSPERO (CRD42024590389). PubMed, Cochrane Library, Web of Science, and Embase were systematically searched until November 2025, Quality assessment and data extraction were performed by two investigators, and the hazard ratios and their corresponding 95% confidence intervals were combined using Stata for data analysis.

Results

A total of 29 studies were included, we found that MASLD were related to colorectal polyps (I² = 62.7, HR = 1.42, 95% CI [1.22–1.66]), colorectal cancer (I² = 82.8%, HR = 1.22, 95% CI [1.16–1.29]), p < 0.001) and esophagus cancer (I² =88.4, HR = 1.14, 95% CI [1.05–1.24], p < 0.001), gastric cancer (I² = 88, HR = 1.18, 95% CI [1.1–1.26]), cholangiocarcinoma (I² = 73.7, HR = 1.26, 95% CI [1.1 7–1. 36], P < 0.001) and gallbladder cancer (I² = 56.1, HR = 1.41, 95% CI [1.03–1.92], P < 0.001). Factors like follow-up time, study methods and countries contributed to heterogeneity of studies. Lastly, incidence rates (IR) and prognosis of GI cancer in patients with MASLD were highly correlated.

Conclusion

We conclude that there is a significant association and prognosis between MASLD and gastrointestinal tumors. Further studies should focus on prospective studies and mechanistic insights.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a major contributor to chronic liver disease, with a global prevalence of up to 30% in adults (Rinella, 2015). In 2020, an international consensus panel redefined NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), also termed metabolic-associated fatty liver disease (MAFLD) (Eslam et al., 2020). Globally, projections indicate that the number of MASLD cases in the United States and Japan could rise from approximately 83 million in 2015 to 101 million by 2030, with up to 15 million of these in the United States and Japan combined (Fan & Li, 2023). Despite this high prevalence, no standardized treatment regimen exists; consequently, management relies on lifestyle modification and off-label pharmacotherapy, which often fail to halt disease progression (Sun et al., 2015). MASLD is regarded as the hepatic manifestation of metabolic syndrome (MetS) because multiple factors disturb metabolism in the liver, pancreas, adipose tissue, and skeletal muscle (Younossi, Kalligeros & Henry, 2025). Common contributors include obesity, type 2 diabetes, and reduced health-related quality of life (Cortez-Pinto et al., 1999).

Gastrointestinal (GI) tumors are associated with poor prognosis and high mortality. GI cancers account for roughly one-quarter of global cancer cases, with particularly high burdens in Asia (Kuntz et al., 2021). Although overall incidence is declining, studies in the United States show that the incidence of specific GI cancers—such as gallbladder and colorectal cancer—continues to rise among adults aged 25–49 years (Ben-Aharon et al., 2023). Rectal and pancreatic cancers are among the most aggressive GI malignancies, and their development is linked to genetic mutations, tumor-suppressor gene inactivation, and DNA damage (Haq et al., 2012).

Recent evidence has implicated MASLD in GI tumorigenesis. Extrahepatic cancers—especially colorectal and gastric cancer—are now the leading cause of death in patients with MASLD as the disease progresses (Fujii et al., 2023). Several studies, such as those of Yang et al. (2023) and Lee et al. (2020), have reported positive associations between MASLD and colorectal polyps or GI cancer. Meta-analyses by Zhou et al. (2024) and Liu et al. (2020) likewise indicate an increased risk of GI cancer among individuals with MASLD. However, these studies were either single-centre investigations with limited sample sizes or did not evaluate prognostic outcomes. Moreover, conflicting results exist: Park et al. (2022) found no association between MASLD and oesophageal cancer, whereas Lan et al. (2022) reported no link with pancreatic cancer. Consequently, the effect of MASLD on the incidence, risk, and prognosis of GI cancers remains unclear.

To address these gaps, we performed a systematic review and meta-analysis of cohort studies to quantify the relationship between MASLD and GI tumors and to assess the influence of MASLD on tumor incidence and prognosis.

Survey methodology

Search strategy

We conducted a systematic search of the PubMed, Cochrane Library, Web of Science, and Embase databases, with a search date concluding in November 2025, to assess the risk and prognosis of gastrointestinal cancers in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We used Medical Subject Headings (MeSH) terms: (nonalcoholic fatty liver disease” or “non-alcoholic fatty liver” or “metabolic dysfunction-associated fatty liver disease or “NAFLD” or “MASLD”) in combination with (“colorectal polyps” or “colorectal adenoma” or “colorectal cancer” or “CRC” or “esophagus cancer” or “gastric cancer” or “cholangiocarcinoma” or “gallbladder cancer” or “gastrointestinal cancer”) in combination with (“associations” or “prognosis”). Our searches were not restricted by gender, ethnicity, or geographic region. Article screening was carried out independently by two researchers (Siyu Duan and Yiyi Wei) and any disagreements were resolved by a third experienced researcher (Yan Gu). After eliminating duplicates, the titles and abstracts of the remaining articles were reviewed to determine the initial article inclusion, and then the final inclusion was determined by reading the full text. The detailed search strategy is provided in the Appendix S1. This systematic review was conducted according to a priori protocol registered with PROSPERO (No. CRD42024590389) to ensure the originality of our selected topic.

Study selection

Inclusion criteria

• 1.Cohort studies that included cancers of the gallbladder, pancreas, and bile ducts. A study population with an age greater than 18 years.
• 2.Patients with a clinically confirmed diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) based on International Classification of Diseases (ICD) codes, imaging techniques, or liver biopsy.
• 3.The outcome was the incidence rate of GI cancers among MASLD, risk of extrahepatic GI cancers and colorectal polyps in patients, prognosis of GI cancer with MASLD compared to individuals without MASLD
• 4.Providing adjusted hazard ratios (HRs) odds ratios (ORs) with their corresponding 95% confidence intervals (CIs)
• 5.Studies with follow- up time at least 1 year and the study with the most comprehensive information
• 6.Studies we included are subject to patients with pathologically confirmed primary GI cancer

Exclusion criteria

• 1.Reviews, conference abstracts, case reports, and monographs.
• 2.Data that could not be obtained from the original article.
• 3.Hepatic cancer with NAFLD
• 4.Patients with metastatic GI cancer

Extraction of data

Two investigators (Siyu Duan and Yiyi Wei) independently screened the titles and abstracts of potential articles. Full texts of potentially relevant studies were reviewed for inclusion if they met the established criteria. Disagreements were resolved through consensus. For articles that met the inclusion criteria, we extracted data encompassing: (1) study characteristics, including the first author, study design, study site, MASLD diagnostic criteria, duration of follow-up, and type of gastrointestinal cancer; (2) population characteristics, including sample size, age, gender, and the distinction between MASLD and metabolic dysfunction-associated fatty liver disease (MAFLD); and (3) outcomes, focusing on the indicators of association between MASLD and gastrointestinal cancers, as well as colon polyps. Odds ratios (OR) and hazard ratios (HR) were included for discussion. Additionally, the incidences of MASLD in relation to gastrointestinal tumors and all-cause mortality were extracted.

Evaluation of literature quality

We assessed the methodological quality of the included case–control and cohort studies with the Newcastle–Ottawa Scale (NOS). The scale evaluates three domains: selection of the study groups, comparability of exposed and unexposed participants, and ascertainment of the outcome. Each study can receive up to nine points; scores of 8–9, 6–7, and ≤5 indicate low, moderate, and high risk of bias, respectively (Stang, 2010). Literature quality was assessed and cross-checked by two reviewers (Siyu Duan and Yiyi Wei) independentaly, and any disagreements were resolved by a third experienced researcher (Yan Gu).

Data analysis

For data related to metabolic dysfunction-associated steatotic liver disease (MASLD) and gastrointestinal tumors, a meta-analysis was conducted using hazard ratios (HR) and odds ratios (OR), with the primary outcome indicator being the occurrence of gastrointestinal cancers (i.e., esophageal, gastric, pancreatic, biliary, and colorectal) as well as colon polyps among patients with MASLD. Secondary outcomes included the incidence profile of MASLD concerning colorectal, and esophageal cancers, as well as all-cause mortality.

All statistical analyses were performed using Stata 15 software. Heterogeneity was assessed using the I² statistic in the forest plot. According to Higgins and Thompson, I² values were categorized as 25%, 50%, and 75%, representing low, moderate, and high heterogeneity, respectively. For outcomes with a sufficient number of studies (≥4), publication bias was evaluated using funnel plots and Egger’s test. High heterogeneity was deemed present if I² > 50%. To explore the source of heterogeneity, subgroup analyses were conducted based on study site, diagnostic method, and follow-up duration. To ensure the robustness of the results, sensitivity analyses were performed by systematically removing each study individually and analyzing the results to verify whether any study significantly impacted the overall findings.

Results

We initially identified 5,657 articles. After removing 1,494 duplicates, we obtained 4,163 articles. Following the application of exclusion criteria based on title and abstract review, 1,363 articles were excluded. Of the remaining 2,800 articles, 2,497 were found to be irrelevant to the study topic, 303 were assessed ultimately, and 274 could not be accessed. Ultimately, 29 studies were included in the analysis (Fig. 1).

Figure 1. Literature screening flowchart.

Basic characteristics of the literature

Among the included literature, there were three case-control studies and 26 cohort studies. MASLD was linked to colon polyps in six studies, colorectal cancer in 14 studies, and prognosis in four studies. Additionally, 12 publications addressed bile duct and gallbladder cancer. MASLD was associated with gastric cancer in 11 articles and esophageal cancer in another 11 articles. The majority of studies were conducted in Asian countries. Diagnostic criteria for MASLD varied across thaae articles, with 19 studies using International Classification of Diseases (ICD) criteria and two studies employing a Fatty Liver Index (FLI) greater than 60 for diagnosis. The specific results are summarized in Table 1. (Hwang et al., 2010; Lee, Lim & Park, 2012; Lee et al., 2015; Lee et al., 2020; Sun et al., 2015; Stepien et al., 2016; Choi et al., 2016; Chen et al., 2017b; Chen et al., 2017a; Chen et al., 2018; Wu et al., 2019; Allen et al., 2019; Wang et al., 2021; Kim et al., 2021; Park et al., 2021; Park et al., 2022; Park et al., 2023; Park et al., 2024; Yamamoto et al., 2021; Liu et al., 2022; Lan et al., 2022; McHenry et al., 2022; Wei et al., 2023; Chung et al., 2023; Yuan et al., 2023; Yu et al., 2023; Yang et al., 2023; Yewan et al., 2024; Li et al., 2025; Tamaki et al., 2025).

Table 1. Basic information of included literatures.

Study	Gender (male/female)	Age (mean)	Sample	Country	Study period	Study design	MASLD diagnosis	Cancer type
Hwang et al. (2010)	/	/	2,917	Korea	2007	retrospective cohort	biopsy	colorectal polyps
Lee, Lim & Park (2012)	0/5,517	35–40	5,517	Korea	2002–2008	retrospective cohort	abdominal ultrasound	colorectal polyps
Lee et al. (2015)	/	66.7	243	Korea	2007–2013	case control	biopsy	Perihilar cholangiocarcinoma
Sun et al. (2015)	1,313/796	61.3	10,545	Korea	1996–2011	retrospective cohort	ICD	GI cancer
Chen et al. (2017b)	/	47.42	2,409	China	/	case control	standard guidelines	colorectal polyps
Chen et al. (2017a)	2,430/1,256	47.97	3,686	China	2014–2016	retrospective cohort	abdominal ultrasound	colorectal polyps
Chen et al. (2018)	0/764	50	764	China	2007–2014	retrospective cohort	abdominal ultrasound	CRC
Wu et al. (2019)	/	18–80	3,262	America	2006–2011	retrospective cohort	ICD	CRC
Wang et al. (2021)	/	52.85	54,187	China	2006–2007	retrospective cohort	abdominal ultrasound	GI cancer
Choi et al. (2016)	1,094/1,301	61.5	2,395	America	2000–2014	case control	/	cholangiocarcinoma
Stepien et al. (2016)	158/128	20–85	286	Europe	7.5 years	prospective cohort	ICD	GBTC
Allen et al. (2019)	2,172/2,550	54	4,722	America	1997–2016	retrospective cohort	ICD	GI cancer
Lee et al. (2020)	4,234,418/3,886,256	46.7	8,120,674	Korea	2009	retrospective cohort	ICD	GI cancer
Kim et al. (2021)	4,659/1,523	43.3	6,182	China	2010–2014	retrospective cohort	abdominal ultrasound	colorectal polyps
Yamamoto et al. (2021)	9,517/20,655	44.3	30,172	Japan	2005–2019	retrospective cohort	ICD	GI cancer
Lan et al. (2022)	55,803/18,104	52.2	73,907	China	2006–2007	prospective cohort	abdominal ultrasound	GI cancer
Liu et al. (2022)	171,746/181,165	57.32	352,911	China	2022	prospective cohort	ICD	GI cancer
McHenry et al. (2022)	136,134/498,936	56	5,000,000	UK	2006–2010	prospective cohort	ICD	GI cancer
Park et al. (2022)	4,234,418	47.4	8,120,674	Korea	2007–2019	prospective cohort	ICD	pancreatic cancer
Chung et al. (2023)	1,066,529	47.5	10,585,844	Korea	2009	retrospective cohort	FLI	GI cancer
Park et al. (2023)	38,900/2,249,890	32.3	5,265,590	Korea	2009–2016	retrospective cohort	ICD	GI cancer
Wei et al. (2023)	19,477/28,324	52.5	47,801	China	2013–2021	retrospective cohort	ICD	GI cancer
Yang et al. (2023)	1,728/1,300	54.3	3,028	China	2018–2023	retrospective cohort	standard guidelines	colorectal polyps
Yu et al. (2023)	642/256	/	898	China	2003–2014	retrospective cohort	ICD	ICC
Yuan et al. (2023)	122,765/36,253	49.9	159,018	China	2006–2014	retrospective cohort	standard guidelines	GI cancer
Park et al. (2021)	4,234,418/3,886,256	46.7	8,120,674	Korea	/	retrospective cohort	ICD	BTC
Yewan et al. (2024)	736,569	53.67	3,596,709	Korea	2011	retrospective cohort	ICD	GI cancer
Li et al. (2025)	23,873	52.62	99,979	China	2006–2011	prospective	ICD	Colorectal cancer
Tamaki et al. (2025)	749,238	44.2	978,607	Japan	2005–2024	prospective	ICD	GI cancer

Notes.

ICD

International classification of disease

FLI

Fatty liver index

GI

Gastrointestinal

BTC

Gallbladder cancer

ICC

Intrahepatic Cholangiocarcinoma

Quality assessment and publication bias

A total of 22 studies scored eight, four studies scored seven, and three studies scored six, indicating that the overall quality of the literature was generally high (Table 2).

Table 2. The Newcastle-Ottawa quality assessment scale (NOS).

First author	Year	Selection	Comparability	Outcome	Overall quality score
		Studies
Choi et al. (2016)	2016	★★	★★	★★	6
Chen et al. (2017b)	2017	★★	★★★	★★★	7
Lee et al. (2015)	2015	★★★	★★	★★★	8
Hwang et al. (2010)	2010	★★	★★	★★	6
Lee, Lim & Park (2012)	2012	★★	★★	★★★	7
Sun et al. (2015)	2015	★★	★★	★★	6
Chen et al. (2017a)	2017	★★	★★★	★★★	8
Chen et al. (2018)	2018	★★	★★★	★★★	8
Wu et al. (2019)	2019	★★	★★	★★★	7
Wang et al. (2021)	2021	★★	★★★	★★★	8
Stepien et al. (2016)	2016	★★	★★★	★★★	8
Allen et al. (2019)	2019	★★	★★★	★★★	8
Lee et al. (2020)	2020	★★	★★★	★★★	8
Kim et al. (2021)	2021	★★	★★★	★★★	8
Yamamoto et al. (2021)	2021	★★	★★★	★★★	8
Park et al. (2022)	2022	★★	★★★	★★★	8
Lan et al. (2022)	2022	★★	★★★	★★★	8
McHenry et al. (2022)	2022	★★	★★★	★★★	8
Liu et al. (2022)	2022	★★	★★★	★★★	8
Chung et al. (2023)	2023	★★	★★★	★★★	8
Park et al. (2023)	2023	★★★	★★	★★★	8
Wei et al. (2023)	2023	★★	★★★	★★★	8
Yang et al. (2023)	2023	★★	★★★	★★★	8
Yu et al. (2023)	2023	★★★	★★	★★★	8
Yuan et al. (2023)	2023	★★	★★★	★★★	8
Park et al. (2021)	2021	★★	★★★	★★★	7
Park et al. (2024)	2024	★★	★★★	★★★	8
Li et al. (2025)	2025	★★★	★★★	★★	8
Tamaki et al. (2025)	2025	★★	★★★	★★★	8

Notes.

NOS: Three domains: participant selection, group comparability, and outcome assessment. Both cohort and case–control investigations could receive 0–9 points; scores ≥ 7 denote high quality, 4–6 moderate quality, and 0–3 low quality.

Incidence of GI cancers among MASLD patients

We conducted an analysis of MASLD in relation to gastrointestinal (GI) cancer rates. We found that patients with colorectal cancer at 10%, cholangiocarcinoma at 4%, and esophagus cancer at 8% (Table 3).

Table 3. Incidence of GI cancers among MASLD patients and incidence rate.

Type	Included studies	Heterogeneity test		Effect model	Meta-analysis results
		I 2	P-value		OR	P-value
a. Colorectal cancer	10	100.00%	0	random	0.12	<0.000
b. Gastric cancer	7
		100.00%	0	random	0.05 (0.01, 0.16)	<0.000
c. Pancreatic cancer	7
		99.99%	0	random	0.05 (0.02, 0.1)	<0.000
d. Esophagus cancer	8
		99.98%	0	random	0.05 (0.02, 0.09)	<0.000
f. Biliary duct cancer	4
		99.97%	0	random	0.06 (0.03, 0.1)	<0.000

Association of MASLD with colon polyps and digestive tract cancers

We derived 6 articles demonstrating that MASLD was associated with colon polyps. The meta-analysis, displayed in a forest plot, revealed high heterogeneity (I² = 62.7%, OR = 1.42, 95% CI [1.22–1.66], P < 0.001). Due to this heterogeneity, we employed a random effects model. Furthermore, three articles indicated that MASLD was associated with colon cancer, which exhibited considerable heterogeneity (I² = 90.2%, OR = 1.85, 95% CI [1.09–3.13]). Three articles each reported association between MASLD with pancreatic cancer (I² = 72.4%, OR = 1.33, 95% CI [1.18–1.49,] P = 0.001), and MASLD with gastric cancer (I² = 50.4%, OR = 1.64, 95% CI [2.1.25 16], P 170 < 0.05). Another three articles indicated that MASLD was related to esophageal cancer, with minimal heterogeneity, leading us to choose a fixed-effects model (I² = 0, OR = 1.41, 95% CI [1.16–1.71], P < 0.05). Furthermore, three articles reported no significant difference in the association between MASLD and cholangiocarcinoma (I² = 48.3%, OR = 1.22, 95% CI [0.94–1.58], P > 0.05) (Table 4).

Table 4. Association of MASLD with colon polyps and digestive tract cancers (OR).

Tumor type	Included studies	Heterogeneity test		Effect model	Meta-analysis results		Publication bias
		I 2	P-value		OR (95% CI)	p-value	Egger
Colorectal polyps	6	67.20%	0.00%	random	1.42 (1.22, 1.66)	0.002	0.323
Colorectal cancer	3	90.20%	0.00%	random	1.85 (1.09, 3.13)	<0.05	/
Pancreatic cancer	3	72.40%	0.01%	random	1.33 (1.18, 1.49)	<0.05	/
Gastric cancer	3	50.40%	0.11%	random	1.64 (1.25, 2.16)	<0.05	/
Esophageal cancer	3	0.00%	0.70%	fixed	1.41 (1.16, 1.71)	<0.05	/
Cholangiocarcinoma	3	48.30%	0.15%	fixed	1.22 (0.94, 1.58)	>0.05	/

In terms of follow-up duration, 14 studies indicated that patients with MASLD had a 1.22-fold increased risk of colorectal cancer compared to normal subjects (I² = 82.8%, HR = 1.22, 95% CI [1.16–1.29], P < 0.001). Due to high heterogeneity, we employed a random effects model for this analysis. Similarly, 11 studies reported that MASLD was associated with a 1.18-fold risk of developing gastric cancer, and we again used a random effects model (I² = 88%, HR = 1.18, 95% CI [1.11–1.26], P < 0.001). Additionally, 12 studies demonstrated that MASLD was associated with a 1.25-fold increased risk of developing pancreatic cancer compared to normal subjects (I² = 56%, HR = 1.25, 95% CI [1.13–1.39], P < 0.001). Furthermore, 12 studies indicated a 1.63-fold risk of esophageal cancer in patients with MASLD (I² = 89%, HR = 1.14, 95% CI [1.05–1.24], P < 0.001). In investigations of cholangiocarcinoma and gallbladder cancer, the risk associated with MASLD was found to be 1.26 (I² = 73.7%, HR = 1.26, 95% CI [1.17–1.36], P < 0.001) and 1.41 (I² = 56.1%, HR = 1.41, 95% CI [1.03–1.92], P < 0.001) times higher, respectively (Table 5).

Table 5. Association of MASLD with colon polyps and digestive tract cancers and publication bias (OR).

Tumor type	Included studies	Heterogeneity test		Effect model	Meta-analysis results		Publication bias
		I 2	P-value		HR (95% CI)	p-value	Egger
Colorectal cancer	14	82.8%	0.00%	random	1.22 (1.16, 1.29)	0.000	0.90
Pancreatic cancer	12	56%	0.001%	random	1.25 (1.13, 1.39)	<0.001	0.65
Gastric cancer	11	88%	0.00%	random	1.18 (1.11, 1.26)	<0.001	0.457
Esophageal cancer	12	89%	0.00%	random	1.14 (1.05, 1.24)	<0.001	0.497
Cholangiocarcinoma	9	73.7%	0	random	1.26 (1.17, 1.36)	<0.001	0.846
Gallbladder cancer	5	56.10%	5.80%	random	1.41 (1.03, 1.92)	<0.001	/

MASLD and prognosis of gastrointestinal cancers

The statistical results from four articles indicated that MASLD significantly affected the all-cause mortality rate of colorectal cancer. Due to high heterogeneity, we selected a random-effects model for the analysis. Patients with MASLD exhibited a 1.26-fold increase in all-cause mortality from colon cancer (I² = 68.5%, HR = 1.26, 95% CI [1.13–1.41], P < 0.001). Furthermore, two articles demonstrated that individuals with MASLD had a 1.86-fold increase in all-cause mortality from esophageal cancer (I² = 95.9%, HR = 1.86, 95% CI [1.7–2.04], P < 0.001). In addition, the all-cause mortality rate of gastric cancer among patients with MASLD was 1.2 times higher than that of normal subjects (I² = 78.8%, HR = 1.2, 95% CI [1.07–1.33], P = 0.001). One article indicated that MASLD was a prognostic risk factor for intrahepatic cholangiocarcinoma (I² = 0%, HR = 2.13, 95% CI [1.59–2.86], P < 0.001) (Table 6).

Table 6. Prognosis of MASLD and digestive tract cancers (HR).

Type	Included studies	Heterogeneity test		Effect model	Meta-analysis results
		I 2	P-value		HR (95% CI)	p-value
a. Colorectal cancer	4	68.50%	0.023	random	1.26 (1.13,1.41)	0.0063
b. Esophagus cancer	2	95.90%	0	random	1.86 (1.7, 2.04)	<0.001
c. Gastric cancer	2	78.80%	0.03	random	1.2 (1.07, 1.33)	0.001
d. Cholangiocarcinoma	1	0.00%	0.4	fixed	2.13 (1.59,2.86)	<0.001

Subgroup analysis

Follow up time

Due to the observed heterogeneity exceeding 80% in colorectal, gastric, and esophageal cancers, we performed subgroup analyses based on follow-up duration, study type, country, and diagnostic methods. We defined 12 years as the cut-off for follow-up duration and found that patients with MASLD had a 1.15-fold increased risk of colorectal cancer during this period compared to normal subjects (I² = 84.3%, HR = 1.15, 95% CI [1.07–1.23], P < 0.05). The risk of developing gastric cancer was 1.17 times higher than the norm (I² = 80.7%, HR = 1.17, 95% CI [1.07–1.29], P < 0.05). Additionally, the risk of esophageal cancer was found to be 1.75 times higher than that of the general population (I² = 88.8%, HR = 1.67, 95% CI [1.36–2.06], P < 0.05) (Table 7).

Table 7. Results of subgroup analysis (follow up time).

Follow up time (years)	Included studies	Heterogeneity test		Effect model	Meta-analysis results
		I 2	P-value		HR (95% CI)	p-value
a.12
Gastric cancer	3	71.20%	0.031	random	1.21 (1.13, 1.3)	<0.001
Esophageal cancer	1	/	/	random	7.25 (2.44, 21.56)	<0.001
Colorectal cancer	2	95.30%	0	random	1.24 (1.09, 1.42)	<0.001
b.>12
Gastric cancer	3	86.50%	0	random	1.79 (0.89, 3.6)	<0.001
Esophageal cancer	4	85.10%	0	random	1.53 (0.97, 2.42)	>0.05
Colorectal cancer	7	82.40%	0	random	1.22 (1.11, 1.34)	<0.001
c.<12
Gastric cancer	4	80.70%	0	random	1.17 (1.07, 1.29)	<0.001
Esophageal cancer	5	88.8%	0	random	1.67 (1.36, 2.06)	<0.001
Colorectal cancer	3	84.3%	0.042	random	1.15 (1.07, 1.23)	<0.001

Study type

In general, our analysis of prospective studies revealed that MASLD was associated with a 1.24-fold increased risk of developing colorectal cancer (I² = 74.1%, HR = 1.24, 95% CI [1.12–1.38], P < 0.05) compared to a 1.18-fold increased risk of gastric cancer (I² = 89.9%, HR = 1.18, 95% CI [1.11–1.26], P < 0.05) (Table 8).

Table 8. Results of subgroup analysis (study type).

Study design	Included studies	Heterogeneity test		Effect model	Meta-analysis results
		I 2	P-value		HR (95% CI)	p-value
Prospective cohort
Gastric cancer	3	89.9	0.962	random	1.18 (1.11, 1.26)	<0.001
Esophageal cancer	3	92.7%	0.001	random	1.42 (1.08, 1.86)	>0.05
Colorectal cancer	4	74.1%	0.002	random	1.24 (1.12, 1.38)	0.049
Retrospective cohort
Gastric cancer	10	89.9%	0	random	1.18 (1.11, 1.26)	<0.001
Esophageal cancer	8	89.7%	0	random	1.57 (1.26, 1.96)	<0.001
Colorectal cancer	10	87.8%	0	random	1.24 (1.22, 1.26)	<0.001

Country

Among the various countries, Korea emerged as the primary source of heterogeneity (Table 9). In Korea, individuals with gastric cancer associated with metabolic dysfunction-associated steatotic liver disease (MASLD) had a 1.16-fold increased risk (I² = 93.2%, HR = 1.16, 95% CI [1.15–1.18], P < 0.05). To further investigate the impact of heterogeneity on the robustness of our results, we excluded the studies conducted in Korea. Following this exclusion, we observed that MASLD exhibited reduced heterogeneity in gastric, esophageal, and colorectal cancers (Figs. 2–4).

Table 9. Results of subgroup analysis (country).

Region	Included studies	Heterogeneity test		Effect model	meta-analysis results
		I 2	P-value		HR (95% CI)	p-value
China groups
Gastric cancer	4	57.40%	0.052	random	1.16 (0.98, 1.37)	>0.05
Esophageal cancer	5	83.50%	0	random	1.39 (0.88, 2.19)	>0.05
Colorectal cancer	6	56.2%	0.01%	random	1.17 (1.11, 1.23)	<0.001
USA groups
Gastric cancer	1	/	/	random	1.64 (1.06, 2.54)	<0.001
Esophageal cancer	2	/	/	/	/	/
Colorectal cancer	1	0.00%	0.60%	random	1.35 (0.75, 2.43)	0.139
Korea groups
Gastric cancer	6	93.2%	0	random	1.16(1.15,1.18)	<0.001
Esophageal cancer	5	89%	0.002	random	1.8(1.46, 2.22)	<0.001
Colorectal cancer	5	96.9%	0	random	1.24 (1.22, 1.26)	<0.001

Figure 2. Results of MASLD and gastric cancer (excluded Korea).

Figure 4. Results of MASLD and colon cancer (excluded Korea).

Figure 3. Results of MASLD and esophageal cancer (excluded Korea).

Diagnostic methods

Among the various diagnostic methods, patients with MASLD diagnosed by abdominal ultrasound exhibited the highest risk of developing gastrointestinal tract cancers. Specifically, the risk of colorectal cancer was 1.41-fold higher compared to that of normal subjects (I² = 63.7%, HR = 1.41, 95% CI [1.15–1.72], P < 0.05). Additionally, the risk of gastric cancer was 1.67-fold higher (I² = 0%, HR = 1.67, 95% CI [1.23–2.27], P < 0.05) (Table 10).

Table 10. Results of subgroup analysis (MASLD diagnostic methods).

Diagnosis	Included studies	Heterogeneity test		Effect model	meta-analysis results
		I 2	P-value		HR (95% CI)	p-value
ICD
Gastric cancer	8	84.6%	0	Random	1.15 (1.08, 1.23)	<0.001
Esophageal cancer	9	90.2%	0	random	1.5 (1.09, 2.08)	<0.001
Colorectal cancer	10	88.5%	0	random	1.24 (1.17, 1.32)	<0.001
Abdominal ultrasound
Gastric cancer	3	0	0.664	random	1.67 (1.23, 2.27)	<0.001
Esophageal cancer	3	85.30%	0.001	random	2.09 (0.75, 5.8)	>0.05
Colorectal cancer	4	63.7%	0.012	random	1.41 (1.15, 1.72)	<0.001
FLI
Gastric cancer	1	/	/	random	1.24 (1.21, 1.27)	<0.001
Esophageal cancer	0	/	/	/	/	/
Colorectal cancer	1			random	1.33 (1.3, 1.37)	<0.001

Notes.

ICD, International classification of disease; FLI, Fatty liver disease.

Nomenclature of FLD

The risk of pancreatic cancer in patients with MASLD was 1.24 (I² = 0%, HR = 1.24, 95% CI [1.18–1.31], P < 0.001), NAFLD was associated with a 1.17-fold risk of developing pancreatic cancer (I² = 29.6%, HR = 1.17, 95% CI [1.1–1.23], P = 0.173). The risk associated with MASLD in gastric cancer is not evident (I² = 95%, HR = 1.13, 95% CI [0.98–1.27], P > 0.05), as well as in esophagus cancer, (I² = 83%, HR = 1.24, 95% CI [0.83–1.65], P > 0.05). In NAFLD, the risk of gastric cancer is 1.21 (I² = 66.2%, HR = 1.21, 95% CI [1.1–1.31], P < 0.001) and 1.57 times in esophagus cancer (I² = 46.4%, HR = 1.57, 95% CI [1.42–1.73], P < 0.001) (Tables S1 and S2).

Publication bias

We assessed publication bias for studies that included more than four pieces of literature and analyzed the data using Egger’s test. The P-value obtained was greater than 0.05, suggesting the absence of publication bias (Egger, Smith & Phillips, 1997) (Table 5). Additionally, we generated funnel plots using Stata 15 and observed that the plots were symmetrical from left to right (Figs. 5–9).

Figure 5. Gastric cancer and MASLD (funnel plot).

Figure 9. Colon cancer and MASLD (funnel plot).

Figure 6. Cholangiocarcinoma and MASLD (funnel plot).

Figure 7. Esophageal cancer and MASLD (funnel plot).

Figure 8. Pancreatic cancer and MASLD (funnel plot).

Discussion

In this updated systematic review and meta-analysis of 29 studies, we found that MASLD was associated with an increased likelihood of developing various extrahepatic cancers, including gastric, colorectal (polyps and cancer), pancreatic, biliary duct and gallbladder cancers as well as influencing prognosis of these cancers. The incidence rate of colorectal cancer in MASLD was about 10%. The risk of gastrointestinal cancers in patients with MASLD was 1.2 to 2 times higher than that of normal subjects over a 12-year follow-up period. Subgroup analysis showed a nearly 1.6-fold to 2-fold increased long-term risk when stratified based on follow-up duration, study type, country, and diagnostic methods. Lastly, we reviewed the literature and focused on colon cancer, gastric cancer, and esophageal cancer as statistical indicators of all-cause mortality. Our findings indicate that esophageal cancer has the highest all-cause mortality rate, with an increase of 86%.

Our results about relationships between MASLD and colon polyps is consistent with a previous study by Chen et al. (2020). This association may be attributed to inflammatory factors released from MASLD, which play a key role in regulating intestinal epithelial cell proliferation and apoptosis, potentially promoting the progression of colorectal polyps (Sanyal et al., 2001). Additionally, a meta-analysis by Mantovani et al. (2022) identified an increased incidence of GI cancer in patients with MASLD. Also, the association between MASLD and gastric and pancreatic cancer are consistent with the study by McHenry et al. (2022) and supports the notion that MASLD is a significant risk factor for pancreatic carcinogenesis. When MAFLD and NAFLD are studied separately, the heterogeneity is reduced compared to when they are combined in pancreatic, gastric and esophagus cancer. However, the risk associated with MASLD in gastric and esophagus cancer is not evident, this may due to the limited studies in MASLD were conducted in 2020–2024 period.

In patients with MASLD who have gallbladder and bile duct cancers, the risk of developing gallbladder cancer is 1.41 times higher than that of normal subjects. However, there are few studies investigating the relationship between gallbladder cancer and MASLD. A study by Liu et al. (2022) reported on the association between 24 gastrointestinal cancers and MASLD, indicating that the risk of gallbladder cancer was 1.26 times higher than that of normal subjects, a conclusion consistent with our meta-analysis. Additionally, a cohort study involving 8 million people conducted by Razumilava & Gores (2014) found that MASLD is positively associated with the development of biliary system cancers. This may be attributed to the fact that MASLD promotes bile duct cancer by inducing hepatic inflammation and cirrhosis, both of which are risk factors for bile duct cancer. We opted to include all MASLD patients in our analysis to explore the association between MASLD and gastrointestinal cancer, thereby minimizing inter-study bias. A prior meta-analysis by Ha, Yim & Karagozian (2023) explored the relationship between lean and fat MASLD and GI cancers, concluding that lean MASLD is associated with a higher risk of developing GI cancers compared to fat MASLD. For instance, the risk of colorectal cancer in patients with lean MASLD is increased by 53% (RR = 1.53, 95% CI [1.12–2.09]). A study by Souza et al. (2024) also found that individuals with lean MASLD are more susceptible to gastrointestinal cancers, potentially due to higher levels of saturated fatty acids (SFA) and the polysaccharide substitution of animal protein intake that are associated with lean MASLD (Amirkalali et al., 2021; Ahmed et al., 2022). Most patients in our cohort were between 50 and 70 years old. In a cross-sectional study by Yuan et al. (2023), the mean age of the population was 49 years, further demonstrating that MASLD is associated with an increased risk of GI cancer in older patients.

Compared to previous meta-analysis, this may be the largest and most comprehensive assessment to date, we incorporated newly published cohort studies from 2021 to 2025. Additionally, we examined the incidence rate and prognosis between MASLD and the risk of several other extrahepatic cancers (colorectal, gastric, esophagus, pancreatic, biliary duct cancers), which have not been explored in previous meta-analyses. However, due to the limited number of studies, evidence for a causal relationship between MASLD and GI-cancer prognosis remains insufficient, highlighting the need for more large-scale studies to validate whether MASLD impacts the prognosis of gastrointestinal cancers.

Given that all diseases share common progress of metabolism, studies also found that MASLD has associations with other non-GI cancers. The possible mechanisms may be that MASLD and cancers share the identical inflammation pathways and MASLD transmits pro-carcinogenic signals to distant organs (Marx, 2004). A meta-analysis conducted by Zhou et al. (2024) found associations between MASLD and thyroid, urinary, breast cancer and female genital cancer. Mantovani et al. (2022) and Liu et al. (2020) also suggested that MASLD increased the development of non-GI cancers. In our study, we mainly focus on the correlations, incidence rate and prognosis of MASLD with gastrointestinal cancers compared with previous analysis, so we do not include the non-GI cancer to make comparisons.

Our study has several strengths. First, it is based on a large sample size of data from individuals aged 50 to 70 years, with follow-up periods predominantly exceeding 10 years, which have a significant disease burden but relatively low incidence. Second, we categorized the included studies by country, study type, and duration of follow-up to explore sources of heterogeneity. We also conducted sensitivity analyses, which showed that excluding any single study did not significantly impact the overall findings, and there was no evidence of publication bias. Furthermore, we included hazard ratios (HRs) adjusted for various confounders, including smoking status, alcohol consumption, physical activity, and diabetes, thereby reducing study bias.

Nevertheless, our meta-analysis has several limitations. First, since most of the included studies were retrospective, we could not establish a definitive prognosis for MASLD. Second, the study population predominantly comprised individuals from asian countries, which may limit the generalizability of our findings. Third, the diagnostic methods for MASLD are not standardized; while the International Classification of Diseases (ICD) and abdominal ultrasound are commonly used, the gold standard for diagnosing MASLD is liver biopsy, contributing to heterogeneity among studies. Finally, there is a paucity of literature regarding the impact of MASLD on all-cause mortality and overall survival in gastrointestinal cancers, making it difficult to conclude that MASLD is a prognostic risk factor for the gastrointestinal tract.

In conclusion, the meta-analysis indicates that MASLD is independently associated with an increased risk of various gastrointestinal cancers, including gastric, colorectal cancer, colorectal polyps, pancreatic, biliary tract, and gallbladder cancers. Although the incidence of gastrointestinal cancers attributable to MASLD is relatively low, early detection and appropriate management of MASLD may help mitigate the risk of these cancers. Furthermore, additional studies on MASLD and all-cause mortality related to gastrointestinal cancers are necessary. Our research findings suggest that clinicians should not only take into account the burden of liver disease associated with MASLD in patient management, but also the relationship between diseases. Further research is needed to investigate the mechanisms underlying these associations.

Funding Statement

This work was supported by National Natural Science Foundation of China, grant number 82203555; Basic and Applied basic Research Foundation of Guangdong Province, grant number 2019A1515110078; Guangdong Science and Technology Project, grant number 2017B020209003; and National Natural Science Foundation of China, grant number 12026605. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.