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15 pages, 6514 KiB

Open AccessArticle

Black Soybean Seed Coat Extract Suppresses Gut Tumorigenesis by Augmenting the Production of Gut Microbiota-Derived Short-Chain Fatty Acids

by Yasuyuki Shimizu, Shunta Hirano, Mohammed Salah, Namiko Hoshi, Yoko Yamashita, Takeshi Fukumoto, Naritoshi Mukumoto, Ai Nakaoka, Takeaki Ishihara, Daisuke Miyawaki, Hitoshi Ashida and Ryohei Sasaki

Cancers 2024, 16(22), 3846; https://doi.org/10.3390/cancers16223846 - 15 Nov 2024

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Abstract

Background: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC). Methods: We fed the APC^min/+ mice, which are highly susceptible to spontaneous intestinal adenoma [...] Read more.

Background: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC). Methods: We fed the APC^min/+ mice, which are highly susceptible to spontaneous intestinal adenoma formation, diets supplemented with or without PACs for 7 weeks and assessed adverse effects, the number and size of intestinal polyps, and the expression of pro- and anti-proliferative proteins in the intestine. The mouse gut microbiome composition was analyzed, and the concentrations of gut short-chain fatty acids (SCFAs) were quantified. We also compared CRC incidence in Tamba in Japan, where black soybean is consumed frequently, with that in the rest of Japan. Results: The number and size of intestinal polyps notably decreased in the PAC-fed mice. Compared with control mice, the PAC-fed mice showed lower expression of proliferation markers proliferating cell nuclear antigen and β catenin and a higher expression of the anti-inflammatory protein oligomeric mucus gel-forming. PAC supplementation increased the prevalence and concentrations of beneficial gut microbes and SCFAs, respectively. Conclusions: Diet supplemented with black soybean-derived PACs could prevent CRC development in mice through gut microbiome remodeling. Regions consuming black soybeans have low CRC incidence. Notably, the incidence of CRC, breast cancer, and liver cancer was significantly lower in Tamba than in the rest of Hyogo Prefecture or Japan. Future studies should delineate the mechanisms underlying the CRC-protective effects of PACs. Nevertheless, our results demonstrate the potential of including PACs in dietary recommendations for cancer prevention. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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9 pages, 922 KiB

Open AccessArticle

The Effect of a Tailored Educational Flyer on Colorectal Cancer Screening Among Rural Residents: Lessons Learned from a Pilot Randomized Trial

by Jungyoon Kim, Cheryl Beseler, Melissa Leypoldt, Roma Subramanian, Tamara Robinson, Karen Funkenbusch, Jason Foster, Susan Harris, Aaron Yoder, Emma Hymel and Shinobu Watanabe-Galloway

Cancers 2024, 16(21), 3645; https://doi.org/10.3390/cancers16213645 - 29 Oct 2024

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Abstract

Background/Objectives: Stool-based tests, such as the fecal immunochemical test (FIT), have been widely used for increasing colorectal cancer (CRC) screening. Small media, such as printed materials or flyers, are known to be an effective intervention to increase CRC screening by fecal tests. [...] Read more.

Background/Objectives: Stool-based tests, such as the fecal immunochemical test (FIT), have been widely used for increasing colorectal cancer (CRC) screening. Small media, such as printed materials or flyers, are known to be an effective intervention to increase CRC screening by fecal tests. However, more evidence is needed to determine whether such small media are effective in improving screening uptake of a mailed FIT intervention targeted at rural populations in the USA. Methods: In this randomized study, 1230 FIT kits were mailed from July to December 2022 to rural Nebraskans aged 45–74 who were not up to date on CRC screening. Half of the participants (n = 608) also received a tailored, one-page, gender-specific educational flyer created based on focus groups with rural residents. Logistic regression was used to determine predictors of returning the FIT. Results: Study participants were predominantly female (76%), non-Hispanic White (83%), and within the age group of 55–64 (43%). Overall, 192 (15.6%) kits were returned (16.1% from the flyer group; 15.1% from the no-flyer group). However, we found no significant differences between the flyer and no-flyer groups (Adjusted Odds Ratio [AOR]: 1.21; 95% CI: 0.88–1.66). Females (AOR: 1.78; 95% CI: 1.19–6.14) and the oldest (65–74) age group (AOR: 5.03; 95% CI: 2.78–8.47) were more likely to return FIT kits than males and the youngest (45–54) age group. Conclusions: A tailored educational flyer was not effective in improving the CRC-screening-rate-by-mailed-FIT approach for rural populations. Future research should explore the content, timing, and mode of delivery of educational interventions as well as other multi-component strategies to improve screening rates. Public health officials might also consider developing strategies targeted at males and younger (45–54) age groups. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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12 pages, 687 KiB

Open AccessArticle

Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components

by Shanmuga Sundaram, Rajan Lamichhane, Alfred Cecchetti, Usha Murughiyan and Uma Sundaram

Cancers 2024, 16(19), 3350; https://doi.org/10.3390/cancers16193350 - 30 Sep 2024

Viewed by 710

Abstract

Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship [...] Read more.

Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM’s Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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11 pages, 1808 KiB

Open AccessArticle

Incidence and Dynamics of CRC Stage Migration: A Regional vs. a National Analysis

by Carol Faris, Araceli Cuaranta, Michael Abdelmasseh, Rob Finley, Barbara Payne, Alexei Gorka and Juan Sanabria

Cancers 2024, 16(19), 3245; https://doi.org/10.3390/cancers16193245 - 24 Sep 2024

Viewed by 591

Abstract

Background/Objectives: Due to an increased rate of surveillance colonoscopy, we aim to determine the impact of stage migration on the incidence and overall survival (OS) of patients who underwent pathological staging of colorectal cancer (CRC) at our Health Network System. Methods: Two datasets [...] Read more.

Background/Objectives: Due to an increased rate of surveillance colonoscopy, we aim to determine the impact of stage migration on the incidence and overall survival (OS) of patients who underwent pathological staging of colorectal cancer (CRC) at our Health Network System. Methods: Two datasets were included: subjects from the tumor registry at a regional Comprehensive Cancer Center (n = 1385) and subjects from the Surveillance, Epidemiology, and End Results (SEER) national database (n = 202,391). Results: A significant increase in the diagnosis of CRC Stage 1 and 4 was observed, with a decrease in stage 2, and no change in Stage 3 in the National datasets (p < 0.01). There was an increase in Stage 4 CRC diagnosis, with a concurrent decrease in stage 2, and no changes in stages 1 and 3 in the regional dataset (p < 0.05). OS followed the expected and progressive decrease in OS by stage (from 1 to 4, p < 0.01). Conclusions: The present findings confirmed CRC stage migration in our Health Network System, along with a national trend conducive to an increased OS for early CRC stages. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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19 pages, 3555 KiB

Open AccessArticle

Refining Risk Criteria May Substantially Reduce Unnecessary Additional Surgeries after Local Resection of T1 Colorectal Cancer

by Fernando Martínez de Juan, Samuel Navarro and Isidro Machado

Cancers 2024, 16(13), 2321; https://doi.org/10.3390/cancers16132321 - 25 Jun 2024

Viewed by 756

Abstract

Background: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Methods: [...] Read more.

Background: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Methods: Logistic regression analysis was performed to determine the association of diverse variables with LNM or ‘poor outcome’ (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. Results: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717–0.880) compared to 0.582 (CI 95% 0.479–0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with ‘poor outcome’, with an AUC of 0.801 (CI 95% 0.731–0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603–0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. Conclusions: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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19 pages, 4452 KiB

Open AccessArticle

Non-Curative Treatment Choices in Colorectal Cancer: Predictors and Between-Hospital Variations in Denmark: A Population-Based Register Study

by Søren Rattenborg, Torben Frøstrup Hansen, Sören Möller, Erik Frostberg and Hans Bjarke Rahr

Cancers 2024, 16(2), 366; https://doi.org/10.3390/cancers16020366 - 15 Jan 2024

Viewed by 1128

Abstract

Background: Variations in treatment choices have been reported in colorectal cancer (CRC). In the context of national recommendations, we aimed to elucidate predictors and between-hospital variations in refraining from curatively intended surgery and adjuvant chemotherapy in potentially curable colorectal cancer. Methods: A total [...] Read more.

Background: Variations in treatment choices have been reported in colorectal cancer (CRC). In the context of national recommendations, we aimed to elucidate predictors and between-hospital variations in refraining from curatively intended surgery and adjuvant chemotherapy in potentially curable colorectal cancer. Methods: A total of 34,116 patients diagnosed with CRC from 2009 to 2018 were included for analyses on non-curative treatment in this register-based study. Subsequently 8006 patients were included in analyses on adjuvant treatment. Possible predictors included patient-, disease-, socioeconomic- and perioperative-related factors. Logistic regressions were utilized to examine the predictors of a non-curative aim of treatment and no adjuvant chemotherapy. Results: The predictors of non-curative treatment were high age, poor performance, distant metastases and being underweight. Predictors for no adjuvant treatment were high age, poor performance, kidney disease, postoperative complications and living alone. For both outcomes we found between-hospital variations to be present. Conclusions: Non-curative overall treatment and refraining from adjuvant chemotherapy were associated with well-known risk factors, but the former was also associated with being underweight and the latter was also associated with living alone. Marked between-hospital variations were found and should be examined further. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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11 pages, 1204 KiB

Open AccessArticle

Gout and Colorectal Cancer Likelihood: Insights from a Nested Case-Control Study of the Korean Population Utilizing the Korean National Health Insurance Service-National Sample Cohort

by Mi Jung Kwon, Kyeong Min Han, Joo-Hee Kim, Ji Hee Kim, Min-Jeong Kim, Nan Young Kim, Hyo Geun Choi and Ho Suk Kang

Cancers 2023, 15(23), 5602; https://doi.org/10.3390/cancers15235602 - 27 Nov 2023

Cited by 2 | Viewed by 1335

Abstract

Considering the global importance of both gout and colorectal cancer (CRC) as significant health issues with mutual relevance, we aimed to examine the risk of colorectal cancer in Korean patients with gout. In this nested case-control study, we used data from 9920 CRC [...] Read more.

Considering the global importance of both gout and colorectal cancer (CRC) as significant health issues with mutual relevance, we aimed to examine the risk of colorectal cancer in Korean patients with gout. In this nested case-control study, we used data from 9920 CRC patients and 39,680 controls the Korean National Health Insurance Service-National Sample Cohort database. Propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounders, were used to assess the odds ratio (OR) and 95% confidence interval (CI) of the association between gout and CRC. Adjusted OR for CRC were similar between patients with gout and the control group (0.95; 95% CI, 0.86–1.04; p = 0.282). However, after adjustment, subgroup analysis revealed an 18% reduction in the probability of CRC among patients younger than 65 years with gout (95% CI, 0.70–0.95; p = 0.009). Conversely, absence of an association between gout and subsequent CRC persisted regardless of sex, income, residence, and Charlson Comorbidity Index score, even among individuals aged 65 years or older. These results imply that gout may not be a significant independent risk factor for CRC among the general population. However, in patients younger than 65 years with gout, a slightly reduced likelihood of CRC was observed. Further research is necessary to establish a causal relationship between gout and CRC and to generalize these findings to other populations. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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12 pages, 1331 KiB

Open AccessArticle

Long-Term Usage of Proton Pump Inhibitors Associated with Prognosis in Patients with Colorectal Cancer

by Chin-Chia Wu, Chuan-Yin Fang, Ben-Hui Yu, Chun-Ming Chang, Ta-Wen Hsu, Chung-Lin Hung, Shih-Kai Hung, Wen-Yen Chiou and Jui-Hsiu Tsai

Cancers 2023, 15(21), 5304; https://doi.org/10.3390/cancers15215304 - 6 Nov 2023

Cited by 1 | Viewed by 1688

Abstract

The dose–response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with [...] Read more.

The dose–response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose–response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04–1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76–0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose–response effect in various dose level. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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12 pages, 1975 KiB

Open AccessArticle

Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience

by Daniel Martinez-Perez, David Viñal, Jesús Peña-Lopez, Diego Jimenez-Bou, Iciar Ruiz-Gutierrez, Sergio Martinez-Recio, María Alameda-Guijarro, Antonio Rueda-Lara, Gema Martin-Montalvo, Ismael Ghanem, Ana Belén Custodio, Lucia Trilla-Fuertes, Angelo Gamez-Pozo, Antonio Barbachano, Javier Rodriguez-Cobos, Pilar Bustamante-Madrid, Asuncion Fernandez-Barral, Aurora Burgos, Maria Isabel Prieto-Nieto, Laura Guerra Pastrian, José Manuel González-Sancho, Alberto Muñoz, Jaime Feliu and Nuria Rodríguez-Salas Show full author list Hide full author list

Cancers 2023, 15(17), 4242; https://doi.org/10.3390/cancers15174242 - 24 Aug 2023

Viewed by 1419

Abstract

Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. Methods: We included all patients with pathologically [...] Read more.

Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. Methods: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. Results: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). Conclusions: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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17 pages, 5373 KiB

Open AccessArticle

Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database

by Fang-Shu Ou, Daniel H. Ahn, Jesse G. Dixon, Axel Grothey, Yiyue Lou, Pashtoon M. Kasi, Joleen M. Hubbard, Eric Van Cutsem, Leonard B. Saltz, Hans-Joachim Schmoll, Richard M. Goldberg, Alan P. Venook, Paulo Hoff, Jean-Yves Douillard, J. Randolph Hecht, Herbert Hurwitz, Cornelis J. A. Punt, Miriam Koopman, Carsten Bokemeyer, Charles S. Fuchs, Eduardo Diaz-Rubio, Niall C. Tebbutt, Chiara Cremolini, Fairooz F. Kabbinavar, Tanios Bekaii-Saab, Benoist Chibaudel, Takayuki Yoshino, John Zalcberg, Richard A. Adams, Aimery de Gramont and Qian Shi Show full author list Hide full author list

Cancers 2023, 15(16), 4117; https://doi.org/10.3390/cancers15164117 - 15 Aug 2023

Viewed by 1974

Abstract

Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement [...] Read more.

Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant. Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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Review

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22 pages, 2899 KiB

Open AccessReview

Colorectal Cancer: Epidemiology, Risk Factors, and Prevention

by Gholamreza Roshandel, Fatemeh Ghasemi-Kebria and Reza Malekzadeh

Cancers 2024, 16(8), 1530; https://doi.org/10.3390/cancers16081530 - 17 Apr 2024

Cited by 18 | Viewed by 12218

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related [...] Read more.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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13 pages, 1278 KiB

Open AccessReview

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer

by Alexandra N. Jones, Katharina M. Scheurlen, Anne Macleod, Hillary L. Simon and Susan Galandiuk

Cancers 2024, 16(7), 1403; https://doi.org/10.3390/cancers16071403 - 3 Apr 2024

Cited by 3 | Viewed by 2224

Abstract

Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor [...] Read more.

Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including ‘EOCRC’, ‘obesity’, ‘obesity-related hormones’, ‘itaconate’, ‘adiponectin’, ‘leptin’, ‘M2a macrophage’, and ‘microbiome’. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC. Full article

(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)

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