Common Risk Factors in Gastrointestinal Cancers: A Narrative Review

Abstract

Gastrointestinal (GI) cancers are among the leading causes of cancer-related morbidity and mortality worldwide, presenting a significant public health challenge. Even with medical research advancements, their incidence remains rising due to modifiable and non-modifiable risk factors across lifestyle, environmental, genetic, and socioeconomic factors. This narrative review identifies and synthesizes key risk factors contributing to GI cancers, including unhealthy diets (high consumption of processed foods, red meat, and added sugars), physical inactivity, obesity, smoking, alcohol use, infections (e.g., Helicobacter pylori), environmental pollution, chronic stress, and socioeconomic disparities. The review emphasizes the interaction among these factors and how this interplay is responsible for the development and progression of GI cancer. It emphasizes the importance of early detection, lifestyle modifications, and public health interventions tailored to specific populations. Understanding these interconnected risk factors provides critical insights for guiding prevention strategies, policymaking, and health education. Addressing modifiable risk factors through a comprehensive, multi-sectoral approach may significantly reduce the global burden of GI cancers and improve long-term health outcomes.

Highlights of the Study

• Identifies common risk factors contributing to gastrointestinal cancers.

• Synthesizes evidence from reviews and original research on gastrointestinal cancer risks.

• Highlights the role of diet, lifestyle, environmental exposures, socioeconomic, behavioral, psychological, and demographic factors.

• Emphasizes the need for targeted preventive strategies to address shared cancer risks.

• Offers actionable insights to guide future research on global cancer prevention and early detection.

Background

Gastrointestinal (GI) cancer, including stomach, colorectal, liver, esophagus, and pancreatic cancers, are a significant global health issue, with more than a quarter of the total number of cancers and result in over a third of cancer-related deaths worldwide [1, 2]. Despite recent decline in gastric cancer incidence, the global rise in colorectal and pancreatic cancers, particularly in low- and middle-income regions, highlights the shifting landscape of GI cancer epidemiology [2, 3]. Geographical disparities are the reflection of lifestyle variations, infections like Helicobacter pylori (H. pylori), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), older populations, and socioeconomic changes [4, 5].

The multifactorial etiology of GI cancers is characterized by modifiable risk factors like a poor diet, smoking, alcohol consumption, physical inactivity, and chronic infection, in addition to genetic predisposition and micronutrient imbalance [6, 7]. While prior studies have addressed risk factors for individual GI cancer types, a comprehensive synthesis of common risk factors across all GI cancers is lacking. This narrative review addresses this gap by integrating current evidence to identify and highlight common and preventable risk factors underlying the development of GI cancers, offering guidance for public health interventions and future research.

In this narrative review, a structured search was conducted across major databases, including PubMed, Semantic Scholar, Web of Science, and Google Scholar, to identify studies published since 2000 addressing common risk factors for GI cancers. Only English-language studies were included to ensure consistency and international applicability. A total of 116 peer-reviewed articles were shortlisted and qualitatively synthesized through a narrative strategy emphasizing dietary, behavioral, environmental, genetic, and socioeconomic risk factors. This structured methodology ensured a thorough and unbiased review of the available literature on common risk factors for GI cancers. A summary of key meta-analyses identified through this narrative review is presented in Table 1, highlighting major associations between risk factors and GI cancer incidence.

Table 1.

Summary of key meta-analyses on GI cancer risk factors

First author	Year	Cancer type	Risk factor	Studies, n	Pooled effect estimate (95% CI or p value)	Result
Meine [8]	2024	GI cancer	Ultra-processed food consumption	5	Colorectal cancer: HR 1.11 (95% CI: 1.03–1.21; p = 0.01; I2 = 31%)	Highest UPF consumption was significantly associated with an increased risk of colorectal, colon, and noncardia gastric cancers. No association was found with hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer
					Colon cancer: HR 1.12 (95% CI: 1.02–1.23; p = 0.02; I2 = 0%)
					Noncardia gastric cancer: HR 1.43 (95% CI: 1.02–2.00; p = 0.04; I2 = 0%)
Zhang [9]	2013	Gastric cancer	Dietary fiber intake	21	OR = 0.58 (95% CI: 0.49−0.67)	Higher dietary fiber intake was inversely associated with gastric cancer risk, with a 44% reduction in risk per 10 g/day increase in fiber intake. The association remained consistent across various subgroup analyses, independent of conventional risk factors
Novianti [10]	2023	Colorectal cancer	Low-fiber diet	14	OR = 0.61 (95% CI: 0.42–0.87)	A significant relationship was found between a low-fiber diet and an increased risk of colorectal cancer. Lack of soluble fiber decreases insulin action and blood sugar control, while insufficient insoluble fiber intake increases mutagen interactions with colonic mucosa
Zamani [11]	2019	GI cancer	Dietary total antioxidant capacity	7	Relative risk (RR)	Dietary total antioxidant capacity (TAC) significantly decreased the risk of GI cancers. The protective effect was observed across different TAC indices (FRAP, TRAP, and TEAC), though further prospective studies are needed to confirm the findings
					FRAP: 0.71 (95% CI: 0.58–0.85), TRAP: 0.65 (95% CI: 0.57–0.75), TEAC: 0.70 (95% CI: 0.59–0.83)
Wang [12]	2020	Digestive system cancers	Omega-3 PUFA intake	25	RR = 0.83 (95% CI: 0.76–0.91)	Higher omega-3 PUFA intake was associated with a 17% reduced risk of digestive-system cancers. The risk reduction varied by cancer site, study location, study design, and other confounding factors such as smoking, alcohol consumption, BMI, and physical activity. No evidence of publication bias was detected
Lu [13]	2022	GI cancer	Omega-3 PUFA supplementation	10	Significant reductions in IL-6 (p = 0.001), CRP (p < 0.00001), and TNF-α (p = 0.0003). Increased CD4+T cells (p = 0.03), CD8+T cells (p = 0.02), and CD4+/CD8+ ratio (p = 0.03). No significant differences in infection complications rate (p = 0.50), prealbumin (p = 0.80), albumin (p = 0.21), or retinol-binding protein (p = 0.80). Length of hospital stay significantly reduced (p = 0.007)	Omega-3 PUFA supplementation improved immune function, reduced inflammation, and shortened hospital stay in GI cancer surgery patients but had no impact on infection complications or nutritional protein levels
Luo [14]	2022	Esophageal cancer	Hot tea consumption	23	OR = 1.79 (95% CI: 1.48–2.15, p = 0.00)	Hot tea consumption was significantly associated with an increased risk of esophageal squamous cell carcinoma (ESCC), but no significant association was found for esophageal adenocarcinoma (EAC)
Wu [15]	2023	Colorectal cancer	Fruit intake	24	Citrus: OR = 0.91 (95% CI: 0.85–0.97)	Higher intake of citrus, apples, watermelon, and kiwi was associated with a reduced risk of colorectal cancer (CRC), with a significant non-linear dose-response relationship for citrus intake. No significant association was found for other fruits
					Apples: OR = 0.75 (95% CI: 0.66–0.85)
					Watermelon: OR = 0.74 (95% CI: 0.58–0.94)
					Kiwi: OR = 0.87 (95% CI: 0.78–0.96)
					Dose-response for citrus: R = −0.0031 (95% CI: −0.0047 to −0.0014)
Di [16]	2023	GI cancer	Meat consumption	40	Red meat and increased cancer risk	Higher consumption of red meat, processed meat, or a combination of both was associated with an increased risk of colorectal cancer (CRC), colon cancer (CC), and rectal cancer (RC). Dietary interventions could be an effective strategy in preventing CRC.
					Colorectal cancer (CRC): RR = 1.09 (95% CI: 1.02–1.16)
					Colon cancer (CC): RR = 1.13 (95% CI: 1.03–1.25)
					Processed meat and increased cancer risk
					Colorectal cancer (CRC): RR = 1.19 (95% CI: 1.13–1.26)
					Colon cancer (CC): RR = 1.24 (95% CI: 1.13–1.26)
					Rectal cancer (RC): RR = 1.24 (95% CI: 1.08–1.42)
					Total red and processed meat consumption and increased cancer risk
					Colorectal cancer (CRC): RR = 1.13 (95% CI: 1.06–1.20)
					Colon cancer (CC): RR = 1.17 (95% CI: 1.04–1.33)
					Rectal cancer (RC): RR = 1.20 (95% CI: 1.04–1.39)
Kim [17]	2019	Gastric cancer	Red, processed, and white meat consumption	43	Red meat and gastric cancer risk: RR = 1.41 (95% CI: 1.21–1.66)	Higher consumption of red and processed meat was associated with an increased risk of gastric cancer, while higher consumption of white meat was associated with a reduced risk. Further research is needed, especially regarding the relationship between white meat and gastric cancer
					Processed meat and gastric cancer risk: RR = 1.57 (95% CI: 1.37–1.81)
					White meat and gastric cancer risk: RR = 0.80 (95% CI: 0.69–0.92)
					Dose-response analysis
					Red meat: RR = 1.26 (95% CI: 1.11–1.42) per 100 g/day increment
					Processed meat: RR = 1.72 (95% CI: 1.36–2.18) per 50 g/day increment
					White meat: RR = 0.86 (95% CI: 0.64–1.15) per 100 g/day increment
Ma [18]	2017	Gastric cancer	Alcohol consumption	10	OR = 1.39 (95% CI: 1.20–1.61)	Alcohol consumption was associated with an increased risk of gastric cancer. Subgroup analysis confirmed that both moderate and heavy drinking contributed to this risk. Effective moderation of alcohol consumption may help reduce the risk of gastric cancer
Xie [19]	2021	Digestive system cancer	Physical activity	47	Overall digestive-system cancer (DSC): RR = 0.82 (95% CI: 0.79–0.85)	Higher physical activity (PA) levels were associated with a reduced risk of digestive-system cancers (DSC), including colorectal, gastric, liver, and pancreatic cancers. Moderate-to-high PA was found to be a protective factor, although variations existed for specific cancers. However, limited evidence suggested that simply meeting international PA guidelines might not significantly reduce DSC risk. Future research is needed to determine the optimal PA levels for cancer prevention
					Colon cancer: RR = 0.81 (95% CI: 0.76–0.87)
					Rectal cancer: RR = 0.88 (95% CI: 0.80–0.98)
					CRC: RR = 0.77 (95% CI: 0.69–0.85)
					Gallbladder cancer: RR = 0.79 (95% CI: 0.64–0.98)
					Gastric cancer: RR = 0.83 (95% CI: 0.76–0.91)
					Liver cancer: RR = 0.73 (95% CI: 0.60–0.89)
					Oropharyngeal cancer: RR = 0.79 (95% CI: 0.72–0.87)
					Pancreatic cancer: RR = 0.85 (95% CI: 0.78–0.93)
					Moderate PA vs. Low PA: RR = 0.89 (95% CI: 0.80–1.00)
					High PA vs. moderate PA: RR = 1.11 (95% CI: 0.94–1.32)
					Meeting PA guidelines and DSC risk: RR = 0.96 (95% CI: 0.91–1.02)
Seyyedsalehi [20]	2023	GI cancer	Dietary nitrate, nitrite, and N-nitroso compounds	40	Overall GI cancer risk (nitrite): RR = 1.18 (95% CI: 1.07–1.29)	Result: The intake of dietary and water sources of nitrate, nitrite, and N-nitroso compounds (NOCs) was associated with an increased risk of gastrointestinal (GI) cancers. Specifically, dietary nitrite was linked to an elevated risk of gastric cancer (GC) and esophageal cancer (EC), while dietary NDMA intake was associated with an increased risk of colorectal cancer (CRC)
					Overall GI cancer risk (NDMA): RR = 1.32 (95% CI: 1.06–1.65)
					Gastric cancer (GC) (nitrite intake): RR = 1.33 (95% CI: 1.02–1.73)
					Esophageal cancer (EC) (nitrite intake): RR = 1.38 (95% CI: 1.01–1.89)
					Colorectal cancer (CRC) (NDMA intake): RR = 1.36 (95% CI: 1.18–1.58)
Pritchett [21]	2022	GI cancer	Outdoor particulate matter air pollution	13	Overall GI cancer risk (PM2.5 exposure): RR = 1.12 (95% CI: 1.01–1.24)	There is some evidence of an association between PM2.5 exposure and gastrointestinal (GI) cancers, with the strongest associations observed for liver and CRCs. While the overall body of evidence is rated as “moderate” in quality, the limited number of studies and inconsistent statistical significance across studies suggest the need for further research
					Liver cancer: RR = 1.31 (95% CI: 1.07–1.56)
					CRC: RR = 1.35 (95% CI: 1.08–1.62)
Liu [22]	2023	GI cancer	Circulating sex hormone levels	29	Gastric cancer: higher SHBG levels → ↑ risk (OR = 1.35; 95% CI: 1.06–1.72), stronger in men (OR = 1.43; 95% CI: 1.10–1.85)	Circulating levels of SHBG and testosterone may play a role in GI cancer risk. SHBG and testosterone were associated with an increased risk of gastric and liver cancer, particularly in men and specific subpopulations, while higher levels of both hormones were linked to a decreased risk of CRC in men but not in women
					Liver cancer
					Higher SHBG levels → ↑ risk (OR = 2.07; 95% CI: 1.40–3.06)
					Higher testosterone levels → ↑ risk (OR = 2.10; 95% CI: 1.48–2.96)
					Stronger associations observed in men (OR = 2.63; 95% CI: 1.65–4.18), Asian populations (OR = 3.27; 95% CI: 1.57–6.83), and hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI: 1.43–10.64)
					CRC (men only)
					Higher SHBG levels → ↓ risk (OR = 0.89; 95% CI: 0.80–0.98)
					Higher testosterone levels → ↓ risk (OR = 0.88; 95% CI: 0.80–0.97)
Luan [23]	2022	Gastric cancer	Sex disparity in gastric cancer	76	Lower incidence in females (p < 0.00001)	Sex-based differences significantly impact clinicopathological characteristics and survival outcomes in gastric cancer. Females have distinct tumor features and better overall survival, but younger female patients may have a worse prognosis. Gender-specific treatment approaches may be necessary for optimal management
					Clinicopathological features in females
					Younger age at diagnosis (p < 0.00001)
					Higher frequency of distal, noncardia, undifferentiated, diffuse, and signet-ring cell carcinoma (p < 0.00001)
					Survival outcomes
					Females had better 3-year (p = 0.0003) and 5-year overall survival (OS) (p < 0.00001), especially among White patients
					Younger female patients had worse 5-year OS compared to males (p = 0.0001)

HR, hazard ratio; OR, odds ratio; RR, relative risk; CI, confidence interval; I², heterogeneity index; FRAP, ferric reducing antioxidant power; TRAP, total radical-trapping antioxidant parameter; TEAC, trolox equivalent antioxidant capacity; NDMA, N-Nitrosodimethylamine; SHBG, sex hormone-binding globulin; PUFA, polyunsaturated fatty acids; PA, physical activity; OS, overall survival.

In the following section, we present the results obtained from the examination of common risk factors for GI cancers. The findings indicate that various factors significantly contribute to the occurrence of GI cancers. An overview of these risk factors is illustrated in Figure 1, which categorizes them into dietary, behavioral, environmental, genetic, socioeconomic, and demographic domains. The analyses reveal that some of the most common risk factors include.

Fig. 1.

Risk factors for GI cancers.

Nutritional Risk Factors

Processed Foods

High consumption of ultra-processed foods is strongly linked to an increased risk of GI cancers, particularly colorectal and noncardia gastric cancers [8]. These foods, rich in refined sugars, unhealthy fats, emulsifiers, and artificial additives, and poor in fiber, vitamins, and antioxidants, contribute to chronic inflammation, oxidative stress, and gut microbiota imbalance, thereby promoting carcinogenesis [24, 25]. Traditional diets like the Mediterranean diet, which emphasize fresh, minimally processed foods, healthy fats, and dietary fiber, offer protective effects against GI cancers [24]. Public health strategies should focus on food labeling and nutrition education to reduce the intake of harmful additives such as emulsifiers. In addition, promoting whole-food diets can significantly lower the burden of GI cancers.

Unhealthy Fats

Unhealthy fats, especially saturated and trans fats, elevate the risk of GI cancers by promoting obesity, chronic inflammation, and gut microbiota disruption [26, 27]. High-fat diets increase intestinal permeability, creating a tumor-promoting environment, while obesity enhances cancer risk through inflammatory mediators like Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) [27]. Conversely, omega-3 fatty acids from sources like fish, flaxseeds, and walnuts may help protect against GI cancers by reducing inflammation and oxidative stress [28]. Public health policies should mandate fat-content labeling, restrict marketing of high-fat foods to children, tax unhealthy fat-rich products, and support healthy eating through education and subsidies.

High Salt Intake

High salt intake is a recognized dietary risk factor for GI cancers, especially the gastric cancer, as excess sodium damages the stomach lining and increases the cancer susceptibility [29]. Its interaction with H. pylori increases bacterial virulence and gastric inflammation, promoting precancerous changes [29, 30]. While the link to gastric cancer is strong, evidence for associations with other GI cancers, like esophageal and colorectal, is less consistent [31]. Public health measures should include sodium labeling, reduced salt in processed foods, and educational initiatives to promote lasting dietary changes.

Added Sugars

The link between added sugar intake and GI cancers is still under investigation, with mixed research findings. Some studies suggest that high consumption of added sugars, especially from sugar-sweetened beverages and processed foods, may raise the risk of certain GI cancers by promoting insulin resistance, inflammation, and gut microbiome imbalance [32, 33]. However, other studies report no consistent association [34, 35]. Regardless, reducing added sugar is important due to its contribution to inflammation and metabolic disorders. Public policies should emphasize clear labeling, restrict marketing to children, tax sugary drinks, and promote nutritional education.

Foodborne Carcinogens

Foodborne carcinogens are significant contributors to GI cancers, particularly through mechanisms involving genotoxicity and the influence of dietary habits. Various compounds, including aflatoxins [36], nitrosamines [36], and polycyclic aromatic hydrocarbons (PAHs) [37], have been linked to increased cancer risks in the GI tract. To lower GI cancer risks, stricter food safety regulations should limit carcinogenic contaminants like aflatoxins, nitrosamines, and PAHs. Enhancing food monitoring, promoting safe cooking practices, and educating the public on healthy food choices are key preventive strategies.

Low Dietary Fiber

Low dietary fiber intake is strongly associated with a higher risk of GI cancers, particularly colorectal cancer (CRC). Insufficient fiber disrupts gut health by impairing bowel function, altering microbiota, and increasing inflammation and carcinogen exposure [9, 10]. A case-control study reported a significantly elevated CRC risk (OR = 7.003) among individuals with low-fiber intake [38]. Fiber supports cancer prevention by producing short-chain fatty acids, diluting carcinogens, and enhancing digestive health. Diets rich in fruits, vegetables, whole grains, and legumes reduce GI cancer risk [39]. Public health strategies should promote fiber consumption through nutrition policies, reformulation, and education in schools, workplaces, and healthcare systems.

Antioxidant Deficiency

The relationship between antioxidants and GI cancers is complex and findings are mixed. A meta-analysis showed that higher dietary total antioxidant capacity is linked to a reduced risk of GI cancers [11]. However, animal studies suggest that antioxidant supplements may promote tumor progression in certain cases, such as Wnt-driven intestinal tumors [40]. Antioxidants can both suppress ROS-induced carcinogenesis and, in some contexts, act as tumor promoters [41]. Therefore, public health policies should promote antioxidant-rich diets fruits, vegetables, nuts, and whole grains, while discouraging high-dose supplementation. Further research is needed to clarify the role of antioxidants in cancer prevention.

Probiotic Depletion

Gut microbiota plays a crucial role in the development and prevention of GI cancers. Probiotics and beneficial gut microorganisms, have shown potential in reducing cancer risk and postoperative inflammation in GI cancer patients [42]. Probiotics can modulate the microbiota toward a healthier state, potentially benefiting cancer patients [43]. Overall, probiotics show promise as an adjuvant or neoadjuvant treatment for cancer prevention and improving therapeutic efficacy [42]. Public health policies should promote probiotic-rich diets and their integration into cancer care to support gut health and reduce GI cancer risk. More research is needed to identify effective strains and optimize their preventive and therapeutic roles.

Omega-3 Fatty Acids Deficiency

Omega-3 polyunsaturated fatty acids have shown potential benefits in preventing and managing GI cancers. A meta-analysis found that omega-3 polyunsaturated fatty acid intake was associated with a 17% reduced risk of digestive-system cancers [12]. Supplementation in GI cancer patients improved immune response, reduced inflammation, and shortened hospital stays [13]. Omega-3 s also enhance the effectiveness of chemotherapy and radiotherapy, aiding in treatment sensitivity and reducing side effects [44]. Public health initiatives should promote omega-3-rich diets and integrate these fats into dietary guidelines and cancer care. Further research is essential to strengthen their role in GI cancer prevention and therapy.

Improper Cooking Methods

Research suggests that certain cooking methods may increase the risk of GI cancers. High-temperature cooking and frying, particularly with heavily browned meat surfaces, have been associated with increased CRC risk [45]. Frequent consumption of fried foods, reuse of cooking oil, and high frying-to-boiling ratios were linked to higher esophageal squamous cell carcinoma (ESCC) risk in high-risk areas [46]. Public health policies should encourage safer cooking methods and raise awareness about the risks of high-temperature techniques, charred foods, and reused oils. Emphasizing healthy preparation practices and supporting research on cooking-related carcinogens can strengthen GI cancer prevention.

Irregular Eating Patterns

Irregular eating patterns have been linked to a higher risk of GI cancers. Unrestrained eating – consuming food without regard to timing or health – has been associated with increased risk of digestive-system cancers, particularly CRC [47]. Skipping or delaying meals by two or more hours also raises the risk of H. pylori infection and gastritis, which are known precursors to gastric cancer [48]. These findings underscore the role of consistent eating habits in cancer prevention. Public health efforts should promote regular meal timing and mindful eating, supported by education and further research on dietary behaviors.

Reliance on Fast Foods

Food insecurity and higher fast food density are associated with increased GI cancer mortality rates, particularly among younger adults and rural populations [49]. The shift from traditional diets to Western-style processed foods, driven by socioeconomic development, contributes to the rising global burden of GI cancers [24]. These findings underscore the importance of addressing fast food consumption and its potential impact on GI health. Public health policies should reduce fast food consumption by promoting access to nutritious, traditional foods, especially in vulnerable groups. Awareness campaigns and efforts to improve food security can help lower GI cancer risk.

Consumption of Hot Beverages

Drinking very hot beverages (above 65°C) has been linked to an increased risk of GI cancers, especially ESCC [14]. Research indicates that temperatures over 60°C can cause cytotoxic effects and accelerate cell division in oral mucosa, contributing to cancer risk without causing direct genetic damage [50]. These findings highlight the importance of avoiding extremely hot drinks for GI cancer prevention. Public health policies should discourage the consumption of very hot beverages and promote safer habits, such as letting drinks cool before intake, through awareness campaigns.

Fruits and Vegetables

Low consumption of fruits and vegetables (F&V) is strongly linked to a higher risk of GI cancers [15, 51]. Diets rich in F&V – especially cruciferous vegetables – have demonstrated protective effects and contribute to overall cancer prevention [52]. Public health strategies should emphasize plant-based diets, promote daily F&V intake in dietary guidelines, and raise awareness about their benefits. Improving access to fresh produce in underserved areas is also crucial to reducing the global GI cancer burden.

Meat Consumption

High red meat intake is associated with an increased risk of colorectal, colon, and rectal cancers, likely due to carcinogenic compounds formed during cooking, such as heme iron, heterocyclic amines, and PAHs [16, 53]. Unlike red meat, which is associated with an increased risk of GI cancers when consumed excessively, white meat, such as poultry and fish, may have protective effects due to its lower saturated fat content and its richness in high-quality proteins [17]. Public health strategies should promote moderation in red meat intake, encourage lean meat alternatives, and educate on safer cooking methods.

Low Water Intake

Emerging evidence indicates a potential link between low fluid intake and increased risk of GI cancers, particularly CRC, as hydration supports digestion and prevents constipation [54, 55]. Public health policies should highlight adequate water consumption as a simple but effective preventive measure, promoting its role in maintaining gut health. To ensure success, inter-sectoral collaboration and political support are essential for improving access to clean water and encouraging healthy hydration habits.

Behavioral Risk Factors

Alcohol Consumption

Alcohol consumption is a major modifiable risk factor for GI cancers, with evidence indicating a dose-dependent relationship – meaning even moderate intake significantly raises cancer risk [56]. A meta-analysis reported a 1.39-fold increased risk of gastric cancer among alcohol consumers. Underlying mechanisms include the production of acetaldehyde, oxidative stress, DNA damage, and impaired nutrient metabolism [18]. Moreover, alcohol has a synergistic effect with tobacco use and obesity, further amplifying GI cancer risk [56]. Therefore, comprehensive public health policies are essential to reduce the alcohol-related cancer burden. These should include stricter regulations on alcohol sales and advertising, public education campaigns on alcohol-related cancer risks, and improved access to prevention and screening programs.

Tobacco Use

Tobacco use is a well-established risk factor for various GI cancers. Harmful compounds in tobacco smoke, such as PAHs and nitrosamines, induce DNA mutations and impair immune function, contributing to carcinogenesis [57, 58]. The risk further increases when combined with alcohol due to synergistic effects [59]. Evidence shows that smoking cessation significantly lowers the risk of GI cancers over time [60]. Effective tobacco control through taxation, smoke-free policies, youth prevention, and public education is essential to reduce smoking prevalence and associated cancer burden.

Physical Activity

Physical inactivity increases the risk of GI cancers by contributing to obesity, insulin resistance, inflammation, and gut microbiota imbalance [61]. In contrast, regular moderate-to-high-intensity physical activity lowers the risk of GI cancers by enhancing metabolic and immune functions [19]. Exercise also reduces insulin levels and improves survival rates among cancer patients [62]. However, excessively high-intensity training may cause adverse GI symptoms and should be approached with caution [63]. Public health initiatives should promote active lifestyles through education, urban design (e.g., walkable cities, bike lanes), and supportive policies to lower GI cancer risk and enhance overall health.

Obesity and Overweight

Obesity is a major modifiable risk factor for GI cancers, linked to increased risks of colorectal, gastric, esophageal, pancreatic, and liver cancers via mechanisms like insulin resistance, chronic inflammation, hormonal changes, and gut microbiota dysbiosis [64, 65]. Although mildly elevated BMI may offer some survival advantages due to early detection, greater nutritional reserves, and treatment tolerance (the “obesity paradox”), severe obesity (BMI ≥35) consistently worsens outcomes [66]. Public health strategies should target obesity prevention through healthy diets, physical activity, regular screening, and personalized education to reduce GI cancer risk and improve patient outcomes.

Infections from Poor Hygiene Practices

Poor hygiene practices contribute significantly to GI cancer development by promoting infections that disrupt gut microbiota and trigger chronic inflammation, DNA damage, and tumorigenesis [67]. Pathogens such as H. pylori, Fusobacterium nucleatum, and Bacteroides fragilis disrupt gut microbiota, induce oxidative stress, and activate inflammation, leading to DNA damage thus promoting tumorigenesis [68, 69]. Notably, some immune responses to infections may also help eliminate early malignant cells, reflecting the dual role of microbial interactions in cancer dynamics [70]. Public health efforts should focus on improving sanitation, hygiene education, access to clean water, and targeted infection screening, while promoting microbiome-supportive strategies like probiotic-rich diets, particularly in low-resource areas.

Environmental Pollution Risk Factors

Water and Food Contamination

Water and food contamination are major environmental risk factors for GI cancers. Dietary intake of nitrates, nitrites, and N-nitroso compounds from processed meats, polluted water, and certain crops have been strongly associated with increased risks of GI cancers [20, 71]. Additionally, chemical pollutants such as chloroform, heavy metals (e.g., arsenic, lead), and pesticide residues contribute to GI malignancies by inducing chronic inflammation, oxidative stress, and DNA damage [71, 72]. Public health policies must enforce stricter food and water safety regulations and limit hazardous chemical use in agriculture and industry. Educational initiatives and sustainable farming practices are essential to reduce exposure to environmental carcinogens.

Exposure to Chemical Toxins

Exposure to chemical toxins such as pesticides, industrial pollutants, heavy metals (e.g., arsenic, cadmium, lead), and persistent organic pollutants like PCBs and dioxins is associated with an increased risk of GI cancers [73, 74]. These agents contribute to carcinogenesis through DNA damage, oxidative stress, and disruption of gut microbiota. Agricultural workers with prolonged exposure face particularly high risks, though proper protective equipment can help reduce harm [75, 76]. Public health policies should implement stricter controls on chemical use, mandate protective measures for workers, and promote safer, environmentally friendly farming practices to lower GI cancer risk.

Air Pollution

Air pollution, particularly fine particulate matter (PM2.5), has been increasingly associated with GI cancers such as liver and CRCs, as well as inflammatory bowel diseases like Crohn’s disease and ulcerative colitis [77, 78]. PM2.5 from sources including vehicle emissions, industrial activity, and biomass burning induces systemic inflammation, oxidative stress, and gut microbiota disruption, all of which contribute to GI carcinogenesis [21]. To reduce related cancer risks, policymakers should enforce air quality standards, support green infrastructure, and promote clean energy. Public education and lifestyle changes are also vital to protect at-risk populations.

Family History

Family history of GI cancers notably increases the risk of both developing and dying from these diseases, particularly in cases such as ESCC and gastric cardia carcinoma [79, 80]. Inherited mutations in genes like CDH1, MLH1, and APC highlight the genetic basis of susceptibility to GI cancers [81]. Early screening, genetic counseling, and personalized preventive strategies are essential for high-risk individuals. Expanding access to genetic services and individualized prevention programs can help reduce the burden of hereditary GI cancers.

Psychological Factors

Chronic Stress

Chronic stress plays a significant role in the initiation and progression of GI cancers, especially gastric and colorectal types. It promotes tumor development by activating β2-adrenergic receptors (ADRB2), leading to oncogenic signaling [82], and disrupts the hypothalamic-pituitary-adrenal axis, altering mediators like corticotropin-releasing hormone, leptin, and ghrelin, which contribute to inflammation and carcinogenesis [83, 84]. Stress management strategies – such as cognitive-behavioral therapy, mindfulness, lifestyle modifications, and β-blockers, can help lower cancer risk and improve outcomes, particularly when integrated into routine care for high-risk individuals.

Anxiety and Depression

Anxiety and depression are common in GI cancer patients, with rates of 20.4% and 30.2%, respectively; highest in those with esophageal cancer [85]. These conditions are more frequent in metastatic cases due to perceived incurability [86], and they negatively affect quality of life, treatment adherence, and survival [87]. The complexity and social burden of cancers like esophageal cancer further heighten the vulnerability to these disorders [88]. Early detection and treatment of anxiety and depression should be integrated into cancer care through access to evidence-based interventions like cognitive-behavioral therapy, mindfulness, and medications. Expanding mental health services in oncology settings is essential, especially for high-risk and underserved populations.

Psychological Trauma

Research indicates a significant relationship between psychological trauma and GI cancer. Patients with post-traumatic stress disorder have substantially higher odds of developing GI cancer compared to non-trauma-exposed individuals [89]. A history of trauma is also linked to greater vulnerability to depression and reduced life satisfaction [90], and is commonly reported among patients with GI complaints, contributing to gut-brain interaction disorders [91]. Implementing trauma-informed care through routine post-traumatic stress disorder screening, access to trauma-focused cognitive-behavioral therapy, and mindfulness interventions can enhance treatment adherence, quality of life, and outcomes in affected patients.

Sleep Disorders

Emerging evidence indicates a link between sleep disorders and an increased risk of GI cancers, particularly gastric, pancreatic, and colorectal types [92]. The risk is notably higher in individuals with coexisting depression [93]. Disrupted sleep-wake cycles, exposure to artificial light at night, and underlying genetic and hormonal factors may mediate this association [94]. Integrating sleep disorder screening into cancer prevention efforts, promoting healthy sleep habits, and addressing related psychological conditions are important strategies for reducing GI cancer risk, especially in high-risk populations.

Demographic Risk Factors

Age

GI cancers are more prevalent in older adults, with approximately 20% of cases occurring in individuals over 80 years old [95]. Age-related molecular changes and weakened immune function contribute to increased vulnerability [96]. Although elderly patients often receive less intensive treatments, evidence suggests that, with appropriate selection, curative options like surgery and adjuvant therapy can offer survival outcomes comparable to younger patients [97]. Therefore, healthcare policies should prioritize equitable access to age-appropriate treatments, early detection, and lifestyle-focused prevention strategies for the elderly population.

Urban vs. Rural Location

Significant disparities exist in GI cancer outcomes between urban and rural populations. Rural residents face higher mortality rates and slower improvement over time [98], while urbanization is linked to increased risks of colon, rectal, pancreatic cancers, and hepatitis C. In urban areas, aging further amplifies GI cancer mortality, particularly for stomach, liver, and CRCs, possibly due to sedentary lifestyles and higher intake of processed foods [99]. These findings underscore the need for targeted strategies to reduce rural healthcare gaps and address urban lifestyle-related risk factors in GI cancer prevention.

Sex

Men face a higher lifetime risk of developing and dying from GI cancers compared to women [100]. This disparity is influenced by hormonal factors, such as higher testosterone and SHBG, which may raise gastric and liver cancer risk in men while potentially reducing CRC risk [22]. Obesity also impacts cancer differently by gender, with men more prone to aggressive tumors [101, 102]. In contrast, women often show better survival in gastric cancer despite earlier onset [23]. These findings highlight the importance of gender-specific prevention and treatment approaches.

Regional and Racial Disparities

Significant regional and racial disparities exist in GI cancer incidence and mortality. Eastern Asia reports the highest rates of gastric cancer, followed by Eastern and Central Europe [103]. In the USA, mortality from gastric, pancreatic, and CRCs is highest in the Southeast [104], with non-Hispanic Blacks experiencing greater incidence and death rates compared to non-Hispanic Whites [105]. In England, most non-White minorities have lower risks, with exceptions like prostate and myeloma in Black populations [106]. Among young adults in the USA, GI cancer incidence is rising, with clear racial and ethnic differences [107].

In Iran, early onset GI cancers vary by province, with rising CRC and notable north-south differences in gastric cancer patterns [108, 109]. African patients tend to be younger and include a higher proportion of women compared to other regions [103]. These differences call for region- and ethnicity-specific interventions, including targeted screening and equitable access to culturally appropriate care.

Economic and Social Risk Factors

Access to Healthcare

Access to healthcare critically influences early diagnosis, treatment, and outcomes in GI cancers. In low- and middle-income countries, insufficient health insurance leads to delayed diagnoses and advanced-stage presentations [110, 111]. Even in high-income countries, disparities persist among marginalized groups such as racial minorities, low-income individuals, and rural populations [112, 113]. Policymakers should expand health insurance coverage and strengthen healthcare infrastructure in underserved regions. Public education and early screening programs must be prioritized to enable timely diagnosis and effective treatment. These measures can reduce disparities and improve GI cancer outcomes globally.

Social and Cultural Environments

Social and cultural factors play a key role in GI cancer risk and outcomes. Limited access to nutritious food, low socioeconomic status, and cultural dietary habits influence both incidence and survival [114, 115]. Lower-income populations often face delayed diagnoses and worse outcomes due to limited healthcare access [116]. Geographic and racial disparities, particularly in the US, reflect systemic issues such as unequal access to preventive care and varying treatment availability among minority groups, contributing to worse GI cancer outcomes [104, 117]. Addressing these issues requires public health policies that promote equitable access to healthy food, healthcare services, and culturally appropriate cancer education.

Interaction between Risk Factors

GI cancers are driven by the combined influence of multiple behavioral risk factors, including smoking, an unhealthy diet, physical inactivity, and alcohol use. While each factor independently increases cancer risk, their interaction creates a synergistic effect that significantly amplifies the likelihood of malignant changes. This occurs through mechanisms such as DNA damage, chronic inflammation, slowed carcinogen elimination, and increased mucosal vulnerability [6, 118].

Smoking exacerbates H. pylori (H. pylori) infection by increasing gastric inflammation and oxidative stress, thereby raising gastric cancer risk. In contrast, dietary antioxidants, such as vitamins C and E, polyphenols, and flavonoids found in F&V, may help protect against this risk, particularly in H. pylori-infected individuals. However, high salt intake and frequent consumption of red or processed meats further elevate the risk, as salt damages the gastric lining and meat-derived nitrates and nitrites can form carcinogens [29, 119, 120].

Individuals with a genetic predisposition to GI cancers may face an increased risk when exposed to factors like smoking, poor diet, and alcohol consumption. Genetic mutations affecting DNA repair or tumor suppressor genes can interact with these lifestyle factors, accelerating cancer onset. The combination of environmental factors, such as a high-salt diet and processed meats, with genetic susceptibility can intensify inflammation in the GI system, promoting carcinogenesis. However, following healthy dietary patterns can reduce GI cancer risk, even for those with high genetic susceptibility [24, 121, 122].

GI cancer risk results from the interaction of genetic, lifestyle, and environmental factors. Healthy habits can lower this risk, even for genetically susceptible individuals. Combined exposure to smoking, poor diet, inactivity, and alcohol greatly increases cancer risk. Public health efforts should integrate prevention strategies, like behavior change, screening, genetic counseling, and H. pylori management, to reduce the overall GI cancer burden. The mechanistic pathways through which these risk factors influence GI carcinogenesis are depicted in Figure 2.

Fig. 2.

Mechanistic pathways leading to GI cancers.

While this narrative review offers a comprehensive synthesis of common risk factors for GI cancers, its findings should be interpreted with caution due to methodological differences among the included studies and the exclusion of grey literature. Additionally, the focus on shared risk factors may overlook cancer-specific determinants.

Future Directions and Research Priorities

To advance GI cancer prevention, future research should prioritize high-quality meta-analyses and longitudinal studies on gene-environment-lifestyle interactions. Including grey literature and unpublished data can address existing knowledge gaps. Emphasis should be placed on personalized strategies, such as gene-environment profiling, plant-based diets, and stress management. Policy efforts must support early detection, reduce environmental exposures, and expand healthcare access, particularly via telemedicine in underserved areas. A multi-sectoral, evidence-based approach is key to reducing the global GI cancer burden.

Policy Implications

Effectively addressing the growing burden of GI cancers requires a multilevel policy approach that integrates prevention, early detection, and equitable access to care. This includes regulating food labeling and environmental exposures, promoting healthy diets and lifestyles, expanding cancer screening and smoking cessation efforts, incorporating mental health support, and reducing healthcare disparities through subsidized services and telemedicine. A coordinated strategy combining regulation, education, and resource allocation is essential for improving outcomes and reducing GI cancer incidence.

Conclusion

GI cancers are a major global health challenge, contributing significantly to cancer-related incidence and mortality. This narrative review highlights common risk factors such as unhealthy diets, environmental pollutants, infections, and genetic predispositions, reflecting the complexity of prevention and management strategies. Despite advances in understanding these risks, disparities in healthcare access, socioeconomic conditions, and public awareness remain, particularly in low- and middle-income countries. Targeted interventions, including health education, dietary improvements, environmental regulation, and psychological support, can help reduce the burden of GI cancers. Future research should focus on gene-environment interactions, the development of personalized prevention strategies, and the use of emerging technologies for early detection and treatment. A comprehensive global approach that integrates public health policy, scientific research, and community engagement is essential to mitigate the impact of GI cancers and improve outcomes for affected populations.

Conflict of Interest Statement

The authors declare no conflict of interest concerning the research, authorship, or publication of this article.

Funding Sources

This study was not supported by any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

Hossein Akhondi: designed the study, drafted the initial manuscript, and coordinated the overall project; Ehsan Allah Kalteh: conducted the literature search, critically reviewed relevant articles, and contributed to the writing process; Mohammad Hassan Lotfi: supervised the manuscript preparation, provided scientific editing, and approved the final version of the manuscript.

Funding Statement

This study was not supported by any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.