Food processing encompasses various techniques used to transform raw foods into forms suitable for cooking, storage, or direct consumption. These processes include grinding, packaging, heating, freezing, washing, and fermenting [1]. In response to concerns over the potential adverse effects of industrial food processing on diet quality and chronic disease risk, food classification systems have been developed to categorize different types of processed foods [2]. Among these, the NOVA classification system is the most widely used; it introduced the term “ultra-processed foods” (UPFs) to describe foods subjected to the highest levels of industrial processing [3]. UPFs are often highly palatable, convenient, shelf-stable, and affordably priced, making them widely accessible and heavily marketed to consumers [4, 5].

Over the past decade, numerous meta-analyses have synthesized research examining the associations between UPF consumption and negative health outcomes [6, 7]. Increased UPF intake has emerged as a major contributor to rising global obesity rates [8], with observational studies consistently linking high UPF consumption to weight gain, overweight status, and obesity [8,9,10,11]. The World Obesity Atlas 2023 report reveals that 38% of people worldwide are classified as overweight or obese, with a body mass index (BMI) exceeding 25 kg/m2 [12]. In industrialized nations, 60–70% of adults have excess body weight. Obesity is a significant risk factor for numerous chronic conditions, including hypertension, dyslipidemia, metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), metabolic dysfunction–associated steatotic liver disease (MASLD), sleep apnea, autoimmune disorders, and various types of cancer in at least 13 different anatomical locations, including endometrial, esophageal, renal, and pancreatic adenocarcinomas, as well as hepatocellular carcinoma, gastric cardia cancer, meningioma, multiple myeloma, and cancers of the colorectum, postmenopausal breast, ovary, gallbladder, and thyroid [13,14,15,16,17,18].

Additionally, an expanding body of research suggests that UPF consumption may be associated with an increased risk of cancer and cancer-related mortality [19]. Recently, several prospective studies have begun exploring the etiological factors underlying obesity in cancer patients, aiming to clarify the links between UPFs, obesity, and cancer [20].

Till now, there are very few recent reviews, mainly systematic or umbrella, focusing on UPF and cancer risk in general or UPF and specific cancers such as gastrointestinal, breast, liver and urological cancers [21,22,23,24,25,26,27,28,29]. This narrative review synthesizes for the first time current evidence on the etiological links between UPF consumption and obesity-related cancer risk, integrating key epidemiological findings to clarify these interconnected health risks. Additionally, it explores potential underlying mechanisms, including the emerging role of gut dysbiosis, to provide a comprehensive understanding of how UPFs may contribute to cancer-related obesity.

Defining Ultra-Processed Foods

The NOVA classification system suggests that excessive consumption of UPFs may pose significant health risks [30]. The detrimental effects associated with UPFs are largely attributed to their nutritional composition and processing methods [30]. UPFs are defined as industrially formulated products composed primarily of chemically altered ingredients, combined with additives to enhance flavor, texture, and appearance [4]. Analyses of global sales data and UPF consumption patterns reveal a notable shift toward a more ultra-processed diet worldwide, although this trend shows considerable variation across regions and countries [31]. For example, the percentage of dietary energy from UPFs varies substantially among high-income countries, ranging from approximately 10% in Italy and 25% in South Korea to as high as 58% in the United States and 42% in Australia [30]. In lower- and middle-income countries, such as Mexico and Colombia, UPFs constitute 16% to 30% of total energy intake, respectively [16]. Over recent decades, the diversity and accessibility of UPFs have expanded rapidly in a wide array of countries with varying economic statuses, especially in densely populated low- and middle-income nations [31,32,33].

Shifts in global dietary patterns from unprocessed and minimally processed foods to UPFs have been largely influenced by food environments, commercial marketing, and consumer behavior. These factors, combined with the distinctive properties of UPFs, raise concerns about overall diet quality and public health [34,35,36]. For instance, UPFs often contain altered food matrices, processing contaminants, and a range of industrial additives, which contribute to less favorable nutrient profiles, characterized by higher energy density, salt, sugar, and saturated fat, and lower levels of fiber, micronutrients, and essential vitamins [37]. While mechanistic research remains in its early stages, accumulating evidence suggests that these attributes may exert compounded or synergistic effects on chronic inflammatory diseases through potential physiological mechanisms, such as gut microbiome dysregulation and increased inflammation [23, 37,38,39].

Given these health implications, the role of UPFs in shaping dietary patterns and serving as modifiable risk factors for chronic diseases and mortality has recently become a focal point for researchers, public health advocates, and the general public.

Ultra-Processed Foods and Obesity: Epidemiological Evidence and Potential Mechanisms

In recent years, a substantial body of research has highlighted the significant association between UPF consumption and the increasing prevalence of obesity, based primarily on observational studies [8]. While this relationship is well-documented among adults, findings in children and adolescents are less conclusive and occasionally conflicting [40]. Meta-analyses consistently demonstrate a dose–response effect, whereby higher UPF intake is associated with an elevated risk of both overweight and obesity [41, 42]. A recent meta-analysis synthesizing data from nine cross-sectional and three cohort studies quantified this association, indicating that each 10% increase in daily caloric intake from UPFs correlates with a 7% and 6% rise in the risk of overweight and obesity, respectively. Notably, this analysis also linked UPF intake to an increased likelihood of abdominal obesity [42]. Reducing UPF consumption is now seen as a promising strategy for both the prevention and management of obesity [42]. A seminal study by Hall et al. explored UPFs’ effect on caloric intake and body weight in a tightly controlled trial involving 20 weight-stable adults, revealing that participants consumed an additional 508 kcal/day on a UPF diet. This caloric increase, largely from higher carbohydrate and fat intake, led to an average weight gain of 0.9 kg, which was reversed during a phase with unprocessed foods [43].

The mechanisms underlying the link between UPF intake and weight gain are multifaceted. UPFs are often low in nutrient density yet high in energy density, which, combined with enhanced texture, taste, and the inclusion of additives that promote hyperpalatability, predisposes individuals to overconsume them. Additionally, UPFs are widely available, affordable, and frequently sold in large portion sizes, with aggressive marketing further driving consumption [44, 45].

Diets high in UPFs are linked to indicators of poor nutritional quality, including elevated levels of added sugars, saturated fats, and sodium, as well as higher energy density. These diets tend to lack essential nutrients, with lower amounts of fiber, protein, and vital micronutrients. UPFs often replace more nutrient-dense options like fruits, vegetables, legumes, nuts, and seeds, reducing the intake of beneficial bioactive compounds such as polyphenols and phytoestrogens. This nutrient-deficient dietary pattern has been associated with the prevalence and development of obesity and related conditions, primarily through inflammatory and oxidative stress pathways [23, 38, 39].

While some researchers argue that nutrient profiling alone can account for the health risks associated with UPFs, recent findings suggest that even when macronutrients are matched, UPF and minimally processed food diets have different effects on energy intake and body weight. Prospective cohort studies further support that the association between UPF consumption and obesity persists even after controlling for overall dietary quality, implying that the effects of UPFs on weight gain extend beyond their nutrient composition [43, 44, 46].

Obesity and Cancer Risk: Pathophysiological Mechanisms and Epidemiological Insights

Obesity, defined by the World Health Organization (WHO) as a BMI over 30 kg/m2, has risen globally at an alarming rate, now posing a major health challenge that affects nearly 600 million adults worldwide [47]. This rapid increase is driven by diverse risk factors, including genetic predisposition and environmental influences such as aging, sedentary lifestyles, and high-calorie diets [48]. Additionally, emerging evidence highlights the role of synthetic chemicals with endocrine-disrupting properties that can alter adipocyte function, further compounding obesity risk [49]. Obesity is linked to numerous chronic conditions, including T2DM, chronic kidney disease (CKD), CVD, and mental health disorders [50,51,52]. Importantly, substantial evidence now connects obesity to an elevated risk of various cancers, while also adversely impacting survival rates and recurrence risks among patients with cancer [53, 54]. Consequently, obesity management has become a critical strategy for improving outcomes in patients with early-stage cancer, underscoring the need for integrated approaches to address both obesity and cancer risk.

The Pathophysiological Link Between Obesity and Cancer Development

As previously discussed, obesity significantly heightens the risk of various cancers, with adipose tissue playing an influential role in cancer metastasis, carcinogenesis, and progression [55, 56]. The mechanisms underlying obesity-associated carcinogenesis are complex and not entirely understood. However, several biological processes are implicated, including immune dysregulation, fatty acid metabolism, extracellular matrix remodeling, hormone dysregulation, alterations in gut microbiota, and chronic inflammation. The impact of these factors may vary across different types of cancers, suggesting distinct mechanistic pathways for each cancer type [57, 58].

One primary mechanism linking obesity to cancer risk involves the function of adipose tissue as an endocrine organ. Adipose tissue, particularly due to the presence of aromatase, converts androgens to estradiol, increasing circulating estrogen levels. This rise in estrogens, predominantly in peripheral adipose tissue, has been linked to a heightened risk of endometrial, breast, and ovarian cancers [59, 60]. The second major mechanism is related to insulin resistance and hyperinsulinemia. Elevated BMI prolongs the action of insulin-like growth factor-I (IGF-1) due to sustained high levels of insulin in individuals with obesity. This condition not only precedes T2DM but is also a known risk factor for cancers, such as those of the prostate, colon, kidneys, and endometrium, driven by increased IGF-1 and insulin [61]. Insulin and IGF activate various tumor-promoting mechanisms in target cells, contributing to processes such as cell proliferation, resistance to apoptosis, angiogenesis, and lymphangiogenesis [62,63,64].

Adipose tissue also secretes adipokines, such as leptin and adiponectin, which contribute to a pro-inflammatory and pro-carcinogenic environment [65]. Obesity is associated with increased levels of leptin, which are linked to inflammation and tumorigenesis, and decreased adiponectin levels, which typically exhibit anti-proliferative properties [66]. Chronic low-grade inflammation stemming from adipocyte hypertrophy and cell death in obesity has emerged as a significant carcinogenic factor, elevating risks for cancers of the liver, biliary tract, and other organs [67]. This inflammatory state is characterized by the release of cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which, in turn, contribute to oxidative stress and DNA damage. Furthermore, structural changes in the tissues surrounding tumors, coupled with altered immune responses, create an environment that promotes cancer progression [67, 68]. Notably, metastasis in obesity-related cancers has been linked to various mechanisms, including angiogenesis, extracellular matrix modulation, metabolic shifts, systemic inflammation, immune cell modulation, adipokines, and extracellular vesicles like exosomes [58]. Figure 1 presents the main key factors linking obesity to cancer.

Fig. 1

Key factors linking obesity to cancer. Abbreviations: IGF-1: Insulin-like growth factor 1; Created in BioRender. Anastasiou IA. (2025) https://BioRender.com/j66y658. Assessed on 18 January 2025

Epidemiological Evidence on Obesity-Related Cancer Risks

Research has indicated that weight gain during adulthood is strongly associated with a higher risk for prostate, colorectal, endometrial, and post-menopausal breast cancers [69]. A significant population-based study involving over 5 million participants showed a strong correlation between increased BMI and the incidence of many common cancers [70]. Further studies utilizing Mendelian randomization techniques have demonstrated a causal relationship between higher body fat and malignancy, including esophageal, gastric, pancreatic, renal, colorectal, ovarian, and endometrial cancers [71,72,73,74,75,76,77].

The International Agency for Research on Cancer (IARC) in 2020 concluded a direct link between obesity and the risk of 13 different cancers, including postmenopausal breast, colorectal, endometrial, esophageal, pancreatic, renal, liver, stomach, gallbladder, ovarian, and thyroid malignancies, as well as multiple myeloma, and meningioma [78]. There is also moderate evidence for associations with other cancers, including diffuse large B-cell lymphoma, throat and laryngeal cancers, prostate cancer, male breast cancer, and oral cancer [