Deciphering the impact of dietary habits and behavioral patterns on colorectal cancer

Abstract

Colorectal cancer (CRC) is a malignant tumor that originates from the epithelial cells of the colon and rectum. Global epidemiological data shows that in 2020, the incidence and mortality rate of CRC ranked third and second, respectively, posing a serious threat to people’s health and lives. The factors influencing CRC are numerous and can be broadly categorized as modifiable and non-modifiable based on whether they can be managed or intervened upon. Non-modifiable factors include age, gender, family history, among others. Among the modifiable factors, dietary habits and behavioral practices are the main intervention measures that people can take to prevent CRC. Numerous studies indicate that a high intake of red and processed meats, fats, as well as habits such as smoking, alcohol consumption, and prolonged sitting, increase the risk of developing CRC. Conversely, consuming ample vegetables, fruits, high dietary fiber, and engaging in moderate regular exercise may reduce the risk of CRC. This article primarily discusses the impact of dietary habits and behavioral practices on the occurrence and development of CRC, along with possible mechanisms, laying the foundation and providing direction for the prevention and control of CRC occurrence and development.

Introduction

Colorectal cancer (CRC), also known as colorectal adenocarcinoma, typically originates from the glandular epithelial cells of the colon. It is a highly malignant tumor with both high incidence and mortality rates. CRC mainly occurs in Europe and the United States, while its incidence has also been rising in Asia in recent decades^[1]. Global cancer epidemiological data shows that in 2020, there were approximately 1.9 million new cases of CRC and around 935 000 deaths. CRC ranked third in terms of incidence and second in terms of mortality rates^[2]. It is projected that by 2040, the global burden of CRC will continue to increase to 3.2 million new cases, with deaths reaching 1.6 million^[3]. Effectively preventing and controlling CRC is a major global public health issue in urgent need of resolution.

The factors influencing CRC are numerous and complex. Current research suggests that it is the result of a combination of various factors, including genetics, environment, and lifestyle^[4]. Based on whether they can be managed or intervened upon, the factors influencing CRC can be broadly categorized into two main groups: modifiable and non-modifiable. Factors such as age^[5-7], gender^[6-8], and family history^[6,9-11] are non-modifiable influences, while lifestyle factors such as smoking^[12,13], alcohol consumption^[14,15], lack of physical exercise^[16,17], and unhealthy diet^[17-19] are modifiable influences. Among these factors, lifestyle, as a modifiable influence, is the focus of our management and intervention. Studies have shown that the majority of CRC occurrences and developments are caused by modifiable lifestyle factors^[20,21]. Research from the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) also indicates that up to 50% of CRC can be prevented by changing lifestyle factors^[22]. Furthermore, by adhering to a healthy lifestyle, the adverse effects of high genetic risk can also be significantly mitigated, leading to a 0.53% absolute reduction in the 5-year risk of CRC^[23]. Therefore, it is crucial to make appropriate lifestyle adjustments for CRC prevention.

As research progresses, more and more factors related to CRC are being discovered. This article primarily discusses the impact of dietary habits and behavioral patterns on the occurrence and development of CRC, as well as possible mechanisms. It is hoped that this article will provide a basis for further identification of potential influencing factors of CRC and the development of effective lifestyle interventions. Moreover, it aims to lay the groundwork and provide direction for better prevention and control of CRC.

Dietary habits and CRC

Figure 1.

The impact of dietary habits on the occurrence of CRC.

Dietary habits play a significant role in the occurrence and development of CRC(Fig. 1). Research indicates that about 80% of CRC cases are related to dietary factors^[24]. Extensive epidemiological studies suggest that the intake of certain foods and nutrients is associated with the risk of developing colorectal tumors^[25,26], and more than half of the risk of colon cancer can be prevented by modifiable risk factors, including diet^[27]. A high-fat diet^[28,29], high intake of red and processed meats^[30,31], and insufficient intake of fruits and vegetables^[21] increase the risk of CRC. However, a diet high in dietary fiber can decrease the risk of CRC. Additionally, food components can affect intestinal health and cancer risk by influencing colonic microbial metabolism^[30].

Red meat and processed meats

Red meat and processed meats are among the most commonly associated foods with an increased risk of CRC^[31]. Excessive consumption of red meat or processed meats can elevate the risk of colorectal adenomas and CRC^[32]. The International Agency for Research on Cancer (IARC) categorizes red meat as “probably carcinogenic to humans” (Group 2A) and processed meats as “carcinogenic to humans” (Group 1)^[33]. Numerous studies suggest that heme and nitrosyl-heme, abundant in red meat and processed meats, promote the occurrence and development of CRC^[32]. Possible mechanisms include: (1) increasing N-nitrosation/oxidative stress, leading to DNA adducts and lipid peroxidation in the intestinal epithelium; (2) directly or indirectly stimulating epithelial proliferation by heme or food-derived metabolites; (3) triggering severe inflammatory responses, initiating a series of malignant processes, among others^[32]. Some studies have also found that red meat and processed meat may increase the risk of CRC by increasing the production of secondary bile acids (BAs), hydrogen sulfide, and trimethylamine oxide through bacteria^[34]. In addition to its association with tumor development, the high choline content in red meat is also linked to tumor progression. Kana Matsuura reported that a choline-deficient diet may impair methionine metabolism, which in turn reduces fibroblast presence in the circulating tumor cell microenvironment and ultimately suppresses tumor metastasis^[35,36].

The Norwegian Women and Cancer (NOWAC) cohort study also found that compared to those who consumed less than 15 grams of processed meat daily, individuals consuming more than 60 grams per day had a significantly increased risk of CRC^[37]. A prospective study from the UK Biobank found that, compared to consuming 21 grams of red and processed meat daily, those with an average daily intake of 76 grams had a 20% higher risk of CRC^[19]. Additional research has indicated a dose-response relationship between red and processed meat intake and CRC risk. In a prospective meta-analysis conducted by Chen et al, the linear dose-response analysis revealed that every 100-gram increase in daily red and processed meat consumption was associated with a 25% increase in colon cancer risk and a 31% increase in rectal cancer risk. However, in the non-linear dose-response analysis, CRC risk increased approximately linearly with higher red and processed meat intake, reaching a plateau around 140 grams per day^[38]. Due to variations in population and subgroup characteristics across studies, the calculated results are not entirely consistent. Nonetheless, nearly all studies confirm that high levels of red and processed meat intake significantly promote CRC development.

High-fat diet

Relevant studies indicate that dietary factors such as high fat, high protein, low vitamin D, and low calcium are considered to be the cause of 80% of colon cancer cases^[39]. The main mechanism involved is the complex interaction between intestinal microbiota and bile acid metabolism^[22].

Under physiological conditions, mitochondria in the colon consume oxygen at a high rate, creating a hypoxic environment in intestinal epithelial cells. This condition favors the growth of obligately anaerobic Clostridia (phylum Firmicutes) while inhibiting the growth of facultatively anaerobic Enterobacteriaceae (phylum Proteobacteria)^[40-42]. Saturated fatty acids prevalent in high-fat diets stimulate mitochondria to produce hydrogen peroxide, which disrupts normal mitochondrial functions, decreases mitochondrial oxygen consumption, and shifts the gut microbiota from strict anaerobes to facultative anaerobes. This increase in the abundance of Enterobacteriaceae enhances the microbiota’s metabolism of choline from high-fat diets, ultimately leading to elevated levels of trimethylamine N-oxide (TMAO) in the blood^[43]. A genome-wide systematic analysis revealed that TMAO shares several genetic pathways with CRC. Moreover, elevated levels of TMAO in circulation are closely associated with an increased risk of developing CRC^[44,45]. Thus, a high-fat diet may promote the occurrence of CRC by regulating the ratio of strict anaerobes to facultative anaerobes, thereby facilitating the production of TMAO from choline degradation. Additionally, a review by Lee et al suggests that a high-fat diet may increase the abundance of facultative anaerobic Enterobacteriaceae, including Escherichia coli, which produce colibactin^[46]. This compound can induce DNA double-strand breaks, thereby promoting carcinogenesis.

BAs synthesized in the liver facilitate the absorption of fats in the small intestine and are reabsorbed during the intestinal transport process, returning to the liver through enterohepatic circulation^[47,48]. A small fraction of BAs that enter the colon undergo complex microbial transformations, producing secondary BAs with tumor-promoting activity^[49]. Elevated concentrations of BAs can be detected in the feces of individuals with CRC, those at high risk of CRC, or healthy individuals on high-fat diets^[50]. Traditional research suggests that elevated concentrations of deoxycholic acid (DCA) and lithocholic acid (LCA) in the colon can stimulate cells and activate the Wnt/β-catenin and NF-κB pathways. This activation leads to DNA oxidative damage, increased mitotic activity, and the activation of intrinsic apoptotic pathways, including mitochondrial oxidative stress, cytochrome C release, and cytoplasmic caspase activation^[51]. Recent studies have found that DCA can also target plasma membrane Ca²⁺ ATPase (PMCA), inhibiting Ca²⁺-nuclear factor of activated T cells 2 signaling. This inhibition reduces the ability of CD8⁺ T cells to kill tumor cells, thereby promoting the development of CRC^[52]. The Farnesoid X Receptor (FXR) is a nuclear receptor that mediates the transcriptional response to BA signaling. Its function is to maintain BA concentrations within physiological ranges, thereby preventing BA-induced cytotoxicity^[53]. When individuals consume high amounts of fat, disturbances occur in the BA pool within the body, resulting in impaired FXR activation. These changes are closely associated with the development of colorectal tumors^[54,55]. The experiments conducted by Fu et al confirmed that when BAs antagonize FXR, they can induce the proliferation and DNA damage of Lgr5+ cancer stem cells. They suggested that FXR might be a potential target for the treatment or prevention of CRC^[56]. APC^Min/+ mice are a classic model for studying spontaneous precancerous lesions in CRC, typically progressing only to the adenoma stage. However, APC^Min/+ mice fed a high-fat diet demonstrate sufficient progression from adenoma to adenocarcinoma, indicating that a high-fat diet can indeed drive the occurrence of CRC. This specific mechanism is related to changes in the abundance of gut microbiota and the composition of the bile acid pool in APC^Min/+ mice^[57].

In a trial investigating how dietary habits affect the risk of colon cancer, African Americans were placed on a high-fiber, low-fat African-style diet, while Africans from rural areas were placed on a high-fat, low-fiber Western-style diet. After a two-week trial period, significant effects on the participants’ colonic microbiota and metabolome were observed due to changes in the fiber and fat content of the diet, particularly in the activation of glycolytic pathways, butyrogenesis, and the inhibition of secondary BA synthesis^[58]. The Alaska Native (AN) population has the highest incidence of sporadic CRC, while the risk is lowest among rural Africans (RA). Another prospective cohort analysis of these two regions similarly found that a low-fiber, high-fat diet led to a higher incidence of CRC in the AN population. Analysis of intestinal microbiota metabolites revealed that the lack of butyrate increased the susceptibility of colonic epithelial cells to deoxycholic acid, which has tumor-promoting activity, thereby increasing the risk of carcinogenesis^[59]. It is evident that the reduction in butyrate levels in the intestine is closely associated with the occurrence of CRC. A large case-control study in Iran analyzed the types of fat and found that high intakes of total fat, cholesterol, and animal-derived fatty acids such as myristic acid, palmitic acid, and palmitoleic acid were associated with an increased risk of CRC. In contrast, certain plant-derived fatty acids, such as heptanoic acid or oleic acid, were found to reduce the risk of CRC^[60].

Vegetables

Most epidemiological studies indicate a protective relationship between vegetable intake and the risk of CRC^[61-64]. Vegetables in the daily diet can promote anti-tumor mechanisms by modulating cell signaling or proliferation pathways^[65]. Studies have found that consuming more cruciferous vegetables (such as broccoli, cabbage, and kale) may reduce the risk of CRC by approximately 8%^[66]. Cruciferous vegetables are rich in glucosinolates and their hydrolysis products, such as indoles and isothiocyanates, which may help reduce the risk of CRC^[67]. The primary mechanisms of action include protecting cells from DNA damage, inactivating carcinogens, and inducing apoptosis in cells with damaged structures^[68]. Indole-3-carbinol (I3C) is a compound found in cruciferous vegetables. Experiments by Amina Metidji et al found that mice fed a diet rich in I3C were protected from intestinal inflammation and CRC. The aryl hydrocarbon receptor (AHR) plays a crucial role in this process, as I3C can activate AHR to restore barrier homeostasis and enhance the negative feedback regulation of the Wnt/β-catenin pathway by transcriptionally regulating Rnf43 and Znrf3, thereby inhibiting tumor formation^[69]. Additionally, studies have shown that another compound from cruciferous vegetables, phenethyl isothiocyanate, can also inhibit the proliferation of tumor stem cells and induce their apoptosis by targeting the Wnt/β-catenin pathway^[70]. Recent studies have also indicated that cruciferous vegetables may enhance the efficacy of cancer treatments and induce chemopreventive effects by regulating key microRNAs^[71]. Additionally, apigenin, a flavonoid commonly found in fruits and vegetables, can exert anti-tumor effects both in vitro and in vivo by targeting the K433 site of PKM2, thereby limiting glycolysis in LS-174T and HCT-8 cells^[72]. Regarding the color of vegetable intake, research has categorized vegetables and fruits into four categories (green, orange/yellow, red/purple, and white) based on the color of their edible parts to explore the relationship between vegetable and fruit color and the risk of CRC. The results showed that in women, intake of green, red/purple, and white vegetables and fruits was negatively correlated with the risk of CRC. In men, intake of orange/yellow vegetables and fruits was associated with an increased risk of CRC^[73].

However, some studies suggest that the relationship between vegetable intake and CRC risk is not clear across different populations and CRC molecular subtypes^[19,74,75]. For instance, a systematic review and meta-analysis by Kashino et al found insufficient evidence to support a relationship between vegetable intake and CRC risk in the Japanese population^[75]. In contrast, significant negative correlations have been observed between vegetable intake and CRC in European and American populations^[76].

Fruits

Currently, a significant body of research suggests a protective relationship between fruit intake and the risk of CRC^[62,63]. Fruits are rich in various nutrients and bioactive compounds such as vitamins, carotenoids, folate, and dietary fiber, which may have preventive effects against cancer^[77]. Anthocyanins are phenolic pigments found in most red, purple, and blue fruits, renowned for their significant antioxidant and anti-inflammatory properties. Numerous experiments have indicated that they can reduce the risk of CRC by targeting multiple signaling pathways involved in CRC development^[78]. A genome-wide interaction study by Nikos Papadimitriou et al investigated the relationship between dietary fiber, fruit, and vegetable intake and CRC risk. The study found that the rs1620977 locus near the NEGR1 gene plays a crucial role in the impact of fruit intake on CRC risk. Specifically, the greater the number of G alleles at this locus, the stronger the protective effect of fruit intake against CRC^[79].

In a prospective cohort study by Terry et al involving Swedish women, it was found that both total intake of fruits and vegetables were inversely associated with the risk of CRC. However, this association was primarily driven by fruit consumption, with fruits showing the strongest association with CRC risk^[64]. Additionally, a meta-analysis conducted in 2023 examined the association between intake of different types of fruits and the incidence of CRC. The results showed that compared to low intake of citrus fruits, apples, watermelon, and kiwi, high intake reduced the risk of CRC by 9%, 25%, 26%, and 13%, respectively. Furthermore, there was a non-linear dose-response relationship between the intake of citrus fruits and the risk of CRC^[80]. Furthermore, a meta-analysis published in 2018, which included data from 19 cohort studies, also demonstrated a significant inverse association between fruit intake and the risk of CRC. The analysis reported a non-linear relationship between fruit intake and CRC risk as well^[81].

However, some studies have not found a significant association between fruit intake and the risk of CRC^[19,82,83]. Furthermore, Hidaka et al suggested that one possible reason for the heterogeneity in current research is that dietary factors may have different effects on different molecular subtypes of CRC. Therefore, they investigated the relationship between intake of fruits, vegetables, and fiber and four molecular subtypes of CRC. The results showed that higher fruit intake was not associated with overall CRC risk. However, there was a statistically significant association between higher fruit intake and reduced risk of BRAF-mutant tumors, while no association was found with the risk of BRAF wild-type tumors^[74]. Yang et al conducted a study using a two-sample Mendelian randomization approach to investigate the causal relationship between fruit intake and CRC. The results showed that fruit intake is associated with a reduced risk of CRC; however, this protective effect was primarily limited to men (OR 0.374; 95% CI: 0.157-0.892; P = 0.027), with no significant effect observed in women^[84].

High-fiber diet

The report from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) states that consuming whole grains, dietary fiber, and dairy products can reduce the risk of CRC^[22]. Dietary fiber is defined to include polysaccharides and lignin, which are found in vegetables in their indigestible forms^[85]. The recommended daily fiber intake is 30-35 g for adult men and 25-32 g for women, which benefits the stability of the gut microbiota and metabolic health. Research shows that dietary fiber reduces the risk of CRC primarily by influencing the composition, diversity, and richness of the gut microbiota, altering butyrate levels, and interacting with BAs^[86,87]. The gut microbiota can further metabolize dietary fiber into short-chain fatty acids, which exert anti-inflammatory and anti-cancer effects^[88]. The source of fiber also influences the prognosis of CRC. Generally, compared to fruits and vegetables, cereal fiber is more effective in reducing the mortality rate of CRC^[89].

In a cross-sectional study, Xie et al found that over the 30-year period from 1990 to 2019, the global burden of CRC attributed to low-fiber diets has decreased. Additionally, the comprehensive exposure value of low-fiber diets has been consistently decreasing in recent years^[90], indicating that people are gradually realizing that increasing dietary fiber intake can reduce the risk of CRC. However, in some industrialized countries, dietary fiber intake remains insufficient. Similarly, in a prospective cohort study, researchers analyzed the relationship between post-diagnosis fiber intake and survival rates in CRC patients. The results showed that for every 5 grams/day increase in fiber intake, the CRC-specific mortality rate decreased by 18% (95% CI, 7-28%, P = 0.002), and the all-cause mortality rate decreased by 14% (95% CI, 8-19%, P < 0.001). This suggests that fiber intake may provide additional benefits to the prognosis of CRC patients^[89]. Another systematic review and meta-analysis study, which included 376 papers, showed that dietary fiber intake had a more pronounced beneficial effect on colon cancer compared to rectal cancer^[91]. However, due to differences in gender and tumor location, there is still limited evidence regarding the correlation between dietary fiber intake and the protective effect against colon cancer. Further research is needed in this area.

Behavioral factors and CRC (Figure 2)

Figure 2.

The impact of behavioral patterns on the occurrence of CRC.

In addition to an unhealthy diet contributing to the occurrence of CRC, this review also explores the association between various lifestyle habits and CRC occurrence from the perspective of behavioral lifestyle factors (Fig. 2).

Cigarette smoking

Current research identifies smoking as a risk factor for CRC. Cigarette smoke can cause dysbiosis in the gut microbiota, particularly by promoting harmful bacteria such as Eggerthella lenta, which increases levels of taurodeoxycholic acid by affecting BA metabolism pathways. This alteration impacts ERK 1/2 phosphorylation, enhancing the activation of the MAPK/ERK signaling pathway and causing colonic epithelial cells to lose their normal proliferation state, ultimately leading to colon tumors. Additionally, cigarette smoke can reduce the expression of tight junction proteins, such as claudin-3 and ZO-1, thereby altering gut metabolism and impairing gut barrier function, which facilitates the penetration of harmful substances^[92]. 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone (NNK), a significant component and major carcinogen among nicotine-derived tobacco-specific nitrosamines, has been shown to upregulate the expression of TMUB1 through the METTL14/YTHDF2-mediated m6A modification pathway. Subsequently, TMUB1 activates the AKT signaling pathway by binding to AMFR, thereby promoting the proliferation and metastatic capability of CRC cells^[93].

A prospective cohort study by Tomotaka Ugai et al found that the extent of macrophage infiltration is crucial for understanding the impact of smoking on CRC. In patients with tumors characterized by low macrophage density, the risk of CRC associated with smoking gradually increases with the duration of smoking history. In contrast, there is no statistically significant association between smoking and the occurrence of CRC with moderate or high macrophage density, nor with CRC classified by M1 or M2 polarized macrophages^[94]. Botteri et al conducted a meta-analysis of 188 original studies and found that compared to never smokers, both current and former smokers had an increased risk of CRC, with relative risks (RRs) of 1.14 and 1.17, respectively. Moreover, the risk of CRC decreased significantly in smokers who had quit for over 25 years compared to current smokers^[95]. Additionally, the risk of CRC increases linearly with smoking intensity and duration^[95]. Furthermore, the severity of smoking’s impact on CRC may vary by gender^[96], with female smokers potentially having a higher risk of developing CRC than male smokers^[13,97]. Research by Gram et al found that smoking increases the risk of CRC differently depending on the anatomical site or gender. Male smokers had an increased risk of left-sided colon cancer (HR = 1.39, 95% CI: 1.16-1.67), while female smokers had an increased risk of right-sided colon cancer (HR = 0.96, 95% CI: 0.80-1.15)^[13]. In 2022, Huang et al conducted a cohort study on the relationship between smoking and CRC survival. The results showed a significant association between smoking and the risk of CRC-related mortality, with smokers having a 1.11-fold increased risk of mortality compared to non-smokers (HR = 1.11, 95% CI: 1.05-1.19)^[98].

Alcohol consumption

Heavy alcohol consumption may be a risk factor for CRC^[14,15,99]. Chen et al found that compared to low alcohol consumption (pure alcohol 0.1 grams/day to <25 grams/day), individuals with a lifetime average alcohol intake of ≥25 grams/day had an 85% increased risk of early-onset CRC (OR = 1.85, 95% CI: 1.23-2.80) and a 27% increased risk of late-onset CRC (OR = 1.27, 95% CI: 1.11-1.45)^[15]. Additionally, a large prospective cohort study in the United States confirmed that heavy alcohol consumption in early adulthood (≥15 grams/day) was associated with a higher risk of CRC (HR = 1.28, 95% CI: 0.99-1.664)^[100]. Alcohol consumption is not only associated with CRC, but there is also a dose-response relationship between alcohol intake and CRC risk^[101,102]. Related studies indicate that alcohol may contribute to the development of CRC by disrupting the composition of the gut microbiota. Additionally, alcohol metabolites can promote the formation of DNA adducts, lipid peroxidation, and oxidative stress, triggering pro-carcinogenic cascades^[103,104]. Recent research has also found that the pathogenic effects of alcohol on CRC may partially stem from DNA methylation, which regulates the expression of COLCA1/COLCA2 genes, thereby contributing to its pathogenicity^[105].

Meta-analysis results by Fedirko et al support that high alcohol intake increases the risk of CRC, and they found a dose-risk relationship between them, demonstrating an association between consuming more than one drink per day and the risk of CRC^[102]. Additionally, in a recent European Prospective Investigation into Cancer and Nutrition (EPIC) study, researchers evaluated the longitudinal changes in alcohol intake among participants at baseline and follow-up and their association with CRC risk. The results revealed that compared to stable alcohol intake, an increase of 12 grams per day in alcohol consumption during follow-up was associated with a 15% relative increase in CRC risk (HR = 1.15, 95% CI: 1.04-1.25), while a decrease of 12 grams per day in alcohol intake was inversely associated with CRC risk (HR = 0.86, 95% CI: 0.78-0.95). Trajectory analysis showed that compared to individuals with low alcohol intake, men who increased their alcohol intake to an average of 30 grams per day from early to late adulthood had a significantly increased risk of CRC (HR = 1.24, 95% CI: 1.08-1.42), whereas no such association was observed in women^[106]. A two-sample Mendelian randomization analysis conducted by Zhang et al demonstrated that weekly alcohol consumption (OR = 1.565, 95% CI = 1.068-2.293, P = 0.022) has a causal relationship with CRC risk, establishing a genetic link between alcohol consumption and CRC.^[107].

Sedentary behavior

Currently, there is ample research evidence suggesting a close association between sedentary behavior and an increased risk of CRC^{[16,17,108,109]}. Sedentary behavior is associated with a 28% to 44% increase in the risk of CRC compared to shorter periods of sitting^[110]. The potential biological mechanisms linking sedentary behavior to increased cancer risk include metabolic dysfunction, changes in circulating levels of sex hormones, and low-grade chronic inflammation throughout the body^[110]. For example, sedentary behavior can lead to increased blood sugar levels, reduced insulin sensitivity, and a heightened risk of diabetes and obesity^[111,112]. Both diabetes and obesity have been identified as significant risk factors for CRC^[113].

However, there is some discrepancy in the findings of studies examining the association between sedentary behavior and CRC. For instance, a case-control study by Hatime examining the impact of physical activity and sedentary behavior on CRC risk in the Moroccan population found a positive correlation between sedentary behavior and rectal cancer (OR = 1.19, 95% CI: 1.01-1.40). However, there was no association with the risk of colon cancer or overall CRC^[114]. Additionally, a meta-analysis by Cong et al found a significant association between sedentary behavior and colon cancer (RR = 1.30, 95% CI: 1.22-1.39), while no statistically significant association was found with rectal cancer. However, subgroup analyses indicated that in specific groups, such as males, cohort studies, and high-quality studies (study quality ≥5), there was a positive correlation between sedentary behavior and rectal cancer risk^[115]. Lee et al conducted a systematic review and meta-analysis on the association between sedentary behavior at work and CRC. The results showed that sedentary behavior at work was associated with an increased risk of both colon cancer (pooled OR = 1.21, 95% CI: 1.11-1.31) and rectal cancer (pooled OR = 1.08, 95% CI: 1.00-1.16)^[109]. Similarly, Boyle et al investigated whether sedentary behavior at work is associated with CRC and if this association varies by site. Their findings indicated that compared to no prolonged sitting, working in a sedentary job for 10 years or more was associated with nearly double the risk of distal colon cancer compared to proximal colon cancer (adjusted OR = 0.94, 95% CI: 1.28-2.93), and a 44% increased risk of rectal cancer (adjusted OR = 1.44, 95% CI: 0.96-2.18)^[116]. An et al also demonstrated a strong association between sedentary behavior and increased CRC risk, with a dose-response relationship observed. For each additional hour of sedentary time per day, the risk of CRC increased by 6% (OR = 1.06, 95% CI: 1.02-1.10)^[117].

Current research findings remain inconsistent, likely due to variations in the populations studied and the methodologies employed. For example, Hatime’s study was a case-control experiment focused on the Moroccan population, while the studies by Cong and Lee were meta-analyses. Considering the hierarchy of evidence in evidence-based medicine, we believe that the latter studies provide a more robust reflection of the association between sedentary behavior and CRC. In summary, it is undeniable that a sedentary lifestyle with a lack of physical activity increases the risk of CRC, and reducing sedentary behavior while engaging in any form of physical activity can lower this risk^[117].

Physical activity

Current research suggests that increasing physical activity is an effective preventive measure for reducing the risk of CRC^[114,118]. In a case-control study conducted in Morocco, Hatime et al investigated the association between physical activity and CRC risk. The results showed that high levels of physical activity were associated with a reduced risk of colon cancer, rectal cancer, and overall CRC^[114]. Similarly, findings from a Mendelian randomization study also support a potential causal relationship between higher levels of physical activity and lower CRC risk, suggesting that enhancing physical activity could serve as an effective strategy for primary cancer prevention^[119]. Furthermore, a prospective cohort study involving the UK Biobank revealed a negative correlation between overall physical activity levels and CRC risk. The study found no heterogeneity between proximal and distal colon cancer, but did not identify any association with rectal cancer^[16]. A recent cross-sectional study investigated the relationship between different types of physical activity (leisure, occupational, and transportation-related) as well as sedentary time and the risk of CRC. The results showed no significant correlation between different types of physical activity and CRC risk. However, as sedentary time decreased, higher levels of physical activity, regardless of the type, were associated with a reduced risk of CRC^[117]. In summary, high levels of physical activity can reduce the risk of CRC^[119], and engaging in physical activity before, during, and after cancer diagnosis can improve the prognosis of CRC^[120].

Conclusion

Currently, CRC is widely prevalent globally, and exploring better ways to prevent and control CRC remains an important direction. With the widespread implementation of early screening for CRC, the prognosis has gradually improved. However, the incidence of CRC remains high, and the impact of unhealthy lifestyles on CRC development cannot be overlooked. Behaviors such as excessive consumption of red and processed meats, fat intake, smoking, alcohol consumption, and prolonged sitting all increase the risk of developing CRC. Conversely, adequate intake of vegetables, fruits, and dietary fiber, as well as moderate and regular physical activity, may lower the risk of CRC. Currently, most studies examining the impact of dietary habits and behaviors on CRC are cohort and cross-sectional studies. Due to differences in tumor subtypes, varying standards among different cohort studies, and the influence of confounding factors, the results may differ slightly. However, the overall trend remains consistent. However, the impact of some potentially protective foods on CRC incidence lacks reliable randomized controlled trials, and recent research indicates that the gut microbiota plays a crucial role in the development of CRC. Further research is needed to clarify the relationship between diet and gut microbiota and how they influence the occurrence and progression of CRC.

In summary, currently, controlling risk factors associated with CRC and advocating for dietary and behavioral habits that may lower its risk can effectively reduce the incidence of CRC and improve its prognosis to some extent. This provides new directions and pathways for early prevention and effective management of CRC.

Ethical approval

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Sources of funding

This study was supported by Natural Science Foundation of Liaoning Province of China (2022-MS-320). The study sponsors took part in conception, design, and manuscript revising.

Author’s contribution

All authors contributed to the selection of topics, writing, and revisions of this review.

Conflicts of interest disclosure

All the authors declare to have no conflicts of interest relevant to this study.

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Guarantor

Zhijun Hong.

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Our paper was not invited.

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