Risk Factor For Colorectal Cancer Research Articles

Colorectal cancer and associated genetic, lifestyle, cigarette, nargileh-hookah use and alcohol consumption risk factors: a comprehensive case-control study

AimThis study aimed to investigate the causes and risk factors of colorectal cancer (CRC) in a Turkish population, focusing on various modifiable and non-modifiable risk factors.MethodsA hospital-based case-control design was employed to compare individuals with CRC (cases) to individuals without CRC (controls). Male and female participants were recruited from the surgery, internal medicine, and out-patient departments. The study encompassed socio-demographic data, clinical information, radiological diagnoses, and biochemical measurements. Univariable and multivariable logistic regressions were used to determine associated risk factors of CRC.ResultsThe study included 704 individuals with CRC and 704 controls. Significant socio-demographic disparities were observed between the groups, with over 30% of the cases having lower levels of education and income compared to the controls. Lifestyle factors such as obesity, higher rates of smoking (cigarettes and hookah) and alcohol consumption were more prevalent among cases than controls. Further significant associations were identified with intestinal inflammation, obesity, processed food consumption, and symptoms such as abdominal pain, cramps, diarrhea, constipation, blood in stool, bloating, irritable bowel syndrome, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Diet analysis revealed that individuals with CRC consumed more red meat, processed and fast foods along with less pulses and vegetables. Genetic predispositions and exposure to chemicals also correlated strongly with increased CRC risk. Multivariable regression analysis identified, nausea/vomiting, constipation, intestinal disease, genetics factor, hookah-nargileh use, history of any cancer, family history of bowel cancer, constipation, cigarette smoking, stress, milk-yogurt consumption, obesity and red meat consumption as significant determinants for CRC.ConclusionCRC risk is influenced by dietary, lifestyle, and genetic factors. Awareness of hereditary risk and participation in screening are crucial. Lifestyle changes, such as avoiding smoking, hookah, and alcohol use, and adopting a healthy diet, are essential for prevention.

DNA methylation-driven gene FAM3D promotes colorectal cancer growth via the ATF4-SESN2-mTORC1 pathway.

Globally, colorectal cancer (CRC) is the malignant tumor with the highest mortality rate after lung cancer. Abnormal DNA methylation drives dysregulated gene expression, thereby promoting CRC progression and leading to poor prognosis. We identified a 3-CpG methylation signature that is independently associated with CRC prognosis. The model consists of three methylation-driven genes: FAM3 Metabolism Regulating Signaling Molecule D (FAM3D), DAPP1, and PIGR. However, the prognostic significance, biological function, and related mechanisms of the individual methylation-driven gene FAM3D in CRC have not been studied. Here, we discovered that FAM3D expression was reduced in CRC tissues and cells, and that high methylation and low expression of FAM3D were independent prognostic risk factors for CRC. In addition, FAM3D promoted the growth and movement of CRC cells in vitro and the proliferation in nude mice, mainly by inhibiting ATF4 transcription and downregulating SESN2 expression, and ultimately activating mTORC1. Furthermore, FAM3D resulted in reduced sensitivity of CRC cells to oxaliplatin, cisplatin, and 5-fluorouracil. Our study showed that FAM3D activates the mTORC1 pathway through the ATF4-SESN2 axis and promotes the malignant progression of CRC, which contributes to predict CRC prognosis and guide individualized treatment.

Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk.

The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case-control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24-1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38-1.78, p = 0.01) for males and 1.25 (95% CI = 1.14-1.38, p < 0.01) for females. Case-control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98-1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case-control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case-control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer.

Modifiable and non-modifiable risk factors of early-onset colorectal cancer: National Health Interview Survey analysis

Background and aimsAlthough the incidence of colorectal cancer (CRC) diagnosed in individuals younger than 50 years, early-onset CRC (EO-CRC), is rapidly increasing, the risk factors for EO-CRC are still being identified. This study aimed to confirm the modifiable and non-modifiable characteristics identified as risk factors for EO-CRC. MethodsThis cross-sectional study used 2004–2018 National Health Interview Survey (NHIS) data, which provides comprehensive health information gathered from national annual household interview surveys. Demographic, clinical, and behavioral characteristics of EO-CRC patients were compared with those without. In addition, their non-age-related characteristics (gender, race/ethnicity, region, body mass index [BMI], alcohol consumption, and smoking status) were compared with individuals with average-onset CRC (AO-CRC). For both comparisons, multivariable logistic regression analyses were performed. ResultsWe identified 156 patients with EO-CRC, 204,846 with non-CRC, and 1972 with AO-CRC. Comparison between the EO-CRC and the non-CRC groups showed that higher odds of having EO-CRC was associated with older age (Odds Ratio [OR]=1.11, 95 % CI=1.08–1.14, p<0.001), living in the Midwest (vs. South) (OR=1.64, 95 % CI=1.06–2.55, p=0.03), and history of alcohol consumption (vs. lifetime abstainer) (OR=2.09, 95 % CI=1.01–4.36, p=0.049). Lower odds of having EO-CRC were associated with being Hispanic (OR=0.43, 95 % CI=0.22–0.84, p=0.01) or Asian (OR=0.38, 95 % CI=0.16–0.92, p=0.03) (vs. non-Hispanic White) and having moderate or vigorous physical activities (vs. no activity) (OR=0.58, 95 % CI=0.34–0.999, p=0.0496 and OR=0.34; 95 % CI=0.21–0.55, p<0.0001, respectively). Compared with patients with AO-CRC, patients with EO-CRC were more likely to be Hispanic (vs. non-Hispanic White) (OR=2.21, 95 % CI=1.13–4.33, p=0.02). ConclusionThis study verified several modifiable (i.e., alcohol consumption and physical activity) and non-modifiable (i.e., race/ethnicity) risk factors while also discovering a new factor (i.e., geographical region) associated with EO-CRC.

Spatial analysis of risk factors related to colorectal cancer in Iran: An ecological study.

Colorectal cancer is the third most common cancer worldwide, accounting for 10% of cancer deaths. Therefore, this study was performed with the aim of spatial analysis of risk factors for colorectal cancer in Iran. This study was conducted ecologically using STEPS information (The WHO Stepwise Approach to NCD Risk Factor Surveillance) in Iran. To analyze the data, the researcher used cluster analysis and Geographically Weighted Regression methods with the help of ArcGIS version 10. The results of OLS analysis showed that there was a significant relationship between tobacco consumption (B = 0.571, p-value = 0.044) and smoking (B = 0.772, p-value = 0.010) and the incidence of colon cancer (CC). There was also a significant relationship between abdominal obesity and the incidence of rectal cancer (RC) (B = 0.061, p-value = 0.027). This study showed that (CC) high-risk areas are located in central and northern parts of Iran, and the significant risk factors related to CC and RC were found to be tobacco use, cigarette smoking, and abdominal obesity. These findings are helpful to inform policymakers to plan screening services to reduce CC and RC, especially in high-risk populations.

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

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.

Spatiotemporal trends in the burden of colorectal cancer incidence and risk factors at country level from 1990 to 2019.

Worldwide, the incidence of colorectal cancer (CRC) continues to rise and remains a major public health concern. This study aimed to analyze the temporal and spatial trends in CRC incidence and related risk factors at the country level. Data on CRC and related risk factors were obtained from the Global Burden of Disease Study (GBD) 2019 study. Temporal trends were evaluated using estimated annual percentage change while spatial trends were analyzed using spatial autocorrelation and autoregression. Additionally, linear mixed-effects models were employed to identify risk factors linked to CRC incidence. Globally, from 1990 to 2019, the incidence cases of CRC increased by 157.23%. At the national level, the incidence of CRC increased in most countries, with the highest increases of age-standardized incidence rate (ASIR) in Equatorial Guinea, Vietnam, and China. In both 1990 and 2019, global spatial clustering of CRC ASIR highlighted hotspots in Europe, characterized by elevated CRC ASIR levels. A comparative analysis of risk factors between hotspot countries and others indicated that gender and alcohol use exerted greater influence in hotspots than elsewhere. Although from 1990 to 2019, the highest growth in ASIR of CRC has been observed in African, Asian, and Latin American countries, the hotspots are still concentrated in Europe. In the identified hotspots, gender and alcohol use exert a more significant impact on CRC incidence compared with other countries. Thus, we should pay attention to countries where the CRC incidence is increasing and these risk factors.

Abstract A048: Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study

Abstract Background: Growing evidence suggests that air pollution may be a risk factor for colorectal cancer (CRC). We examined the association between ambient particulate matter (PM) exposure and CRC risk within the Multiethnic Cohort Study (MEC), representing the first study to include a large sample of racial and ethnic minoritized populations. Methods: The MEC is a prospective study that recruited, from 1993 through 1996, men and women ages 45-75 years largely from five racial and ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and Non-Hispanic White) living in Hawai‘i and California. This study included 98,675 California MEC participants, residing predominately in Los Angeles County. Satellite-based PM2.5 (PM with an aerodynamic diameter &amp;lt;2.5μm) exposures were estimated from a published spatiotemporal model. Kriging interpolation was used to estimate PM10 (PM &amp;lt;10μm) exposures using routine air monitoring data from the US Environmental Protection Agency. Time-varying PM exposures were assessed from time of recruitment through 12/31/2018. Incident invasive CRC cases were identified via linkage with the California Cancer Registry (n=3,217). Cox proportional hazards models were used to examine the association between PM and CRC risk using age as the time metric, with strata defined by age at cohort entry and race and ethnicity, and adjusting for demographic and lifestyle factors. Heterogeneity of the PM-CRC association was assessed by sex, race and ethnicity, and CRC subsite (right colon, left colon, rectum). Results: Risk of CRC increased with PM2.5 (per 10μg/m3 hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.96-1.33) with a larger HR observed among females (HR 1.29, 95% CI 1.03-1.62) than males (HR 0.96, 95% CI 0.76-1.22) (Pheterogeneity=0.24). CRC risk was positively associated with PM2.5 across race and ethnicity (except for African American participants) with the largest HR observed among Latino participants (HR 1.47, 95% CI 1.03-2.08) (Pheterogeneity=0.20). There was no statistically significant heterogeneity of PM2.5 effect by tumor subsite (Pheterogeneity=0.07); although larger HRs were seen for left colon (HR 1.52, 95% CI 1.08- 2.14) and rectal cancers (HR 1.54, 95% CI 1.05-2.25) than right colon cancers (HR 1.09, 95% CI 0.88-1.35). PM10 was not associated with CRC risk (per 10 μg/m3; HR 1.02, 95% CI 0.93-1.22) with no evidence of heterogeneity in associations by sex or race and ethnicity (respective Pheterogeneity 0.75, 0.44). Although HRs for PM10 appeared to differ by CRC subsite (Pheterogeneity=0.03), the 95% CI of these HRs included the null (right HR 0.95, 95% CI 0.84-1.06; left HR 1.13, 95% CI 0.95-1.35; rectal HR 1.18, 95% CI 0.97-1.43). Conclusions: Preliminary findings suggest that PM2.5 exposure is associated with CRC risk with larger associations in females and, possibly, for left colon and rectal cancer. Additional studies are needed to confirm these findings and evaluate the potential biological pathways underlying these associations. Citation Format: Ugonna Ihenacho, Chiuchen Tseng, Jun Wu, Scott Fruin, Timothy V. Larson, Salma Shariff-Marco, Loïc Le Marchand, Daniel O. Stram, Lynne R. Wilkens, Christopher A. Haiman, Beate Ritz, Iona Cheng, Anna H. Wu. Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A048.

Abstract A009: Determinants of increased generalized self-efficacy among Hispanic/Latino colorectal cancer patients participating in a Cancer Moonshot Study

Abstract Background: Colorectal cancer (CRC) accounts for a greater proportion of all cancer deaths among Hispanic/Latino/a/x (H/L) individuals compared to Non-Hispanic White (NHW) subjects. However, the tumor landscape and key determinants of outcomes for CRC among H/L patients remain understudied. Methods: As a Cancer Moonshot initiative, we launched the “Enfrentando el Cancer en Comunidad” (ENLACE) study, which engages H/L CRC patients to characterize their germline genetics and tumor genomic landscape, and to collect data to identify determinants of participation in genetics/genomics research and cancer outcomes. H/L CRC patients &amp;gt;=18 years of age are being recruited from two healthcare facilities: a safety-net hospital, Los Angeles General Medical Center (LA Gen), and a university medical center, USC Norris Comprehensive Cancer Center (Norris). An H/L bilingual team administered surveys to assess patient demographics, acculturation level, Latino values, health literacy, numeracy, CRC risk factors, genetics knowledge (Knowgene scale), and generalized self-efficacy (GSE) upon recruitment for the study, and after return-of-results (ROR) of somatic and germline testing. Results: 165 H/L CRC patients have joined the ENLACE study, with 105 completing baseline surveys (56 male, median age 53 (IQR = 45-60)), and 39 with finalized ROR. Most of the participants self-identified as White (58.1%), were Mexico-born (52.4%), and married (50%). Patients from Norris (n = 33) were more likely to be US-born (55%), college graduates (21%), and annually earn at least $100,000 (69%) while employed full-time (45%) than LA Gen patients (all p-values &amp;lt;0.01). Additionally, Norris patients had higher numeracy and health literacy scores at baseline than LA Gen (p = 0.006 &amp; p = 0.042, respectively). LA Gen patients (n = 72) showed higher scores for familism, respect, traditional gender roles, material success, and mainstream values in the Latino-American cultural values scale (all p-values &amp;lt; 0.05). Higher levels of GSE across all patients were associated with increased numeracy (p = 0.014). LA Gen participants with a higher score for GSE, had on average, higher subscores for material success (p = 0.011), competition and personal achievements (p = 0.07), and mainstream values (p = 0.051), and decreased uncertainties about genetic testing (p = 0.05). A multivariable logistic regression model adjusted for treatment facility, acculturation, age, gender, and income reported that a 1 unit increase in numeracy was statistically significantly associated with 1.62 times the odds of having a greater than the median GSE score (95% CI: 1.09-2.39, p = 0.016). After ROR, a decrease in the number of times participant selected “Don’t know” in the KnowGene scale was reported (p &amp;lt;0.001). Conclusion: We report differences in baseline characteristics for ENLACE participants across healthcare facilities and determinants of generalized self-efficacy. These findings can help inform future interventions to improve self-efficacy and optimize engagement of H/L patients navigating CRC treatment. Citation Format: Joel Sanchez Mendez, Carmen Chavez, Lucia Enriquez, Julie O Culver, Charité N Ricker, Natalia Gutierrez, Sandra Algaze, Lourdes Baezconde-Garbanati, John D. Carpten, Heinz-Josef Lenz, Mariana C. Stern. Determinants of increased generalized self-efficacy among Hispanic/Latino colorectal cancer patients participating in a Cancer Moonshot Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A009.

Who should be screened for colorectal cancer and how can it be prevented more effectively?

In this editorial, we comment on the article published by Agatsuma et al in a recent issue of the World J Gastroenterol (2024; 30: 1368-1376). We firmly concur with Agatsuma et al regarding the vital significance of colorectal cancer (CRC) screening as a public health strategy to diminish disease burden. Individuals exposed to risk factors for CRC, those with comorbid conditions, and those with limited health literacy should undergo screening. However, we believe that more regular screenings should be accompanied by a greater focus on primary prevention (PP) of CRC. CRC remains a significant global health challenge, and its incidence is strongly linked to age, lifestyle, and socioeconomic factors. It is particularly noteworthy that the majority of CRC patients are diagnosed outside of established screening pathways and frequently at an advanced stage of the disease, and the majority of patients possess inadequate or even nonexistent knowledge regarding CRC, which significantly impacts the prognosis and imposes a substantial economic burden. This study revealed that CRC identified during hospital visits for comorbid conditions was typically diagnosed at an earlier stage than detected via symptomatic pathways. Remarkably, early incidental detection of CRC aligns closely with the timing of discovery through routine cancer screenings. This suggests that by adopting more inclusive screening protocols that combine opportunistic testing with traditional screening methods, health care systems can create a more comprehensive safety net for individuals at risk of CRC. However, before maximizing the health benefits of screening programs, it is essential to make additional efforts prior to screening, such as raising awareness via public education, risk assessment, and personalized recommendations, enhancing the knowledge and skills of health care professionals, optimizing the accessibility and convenience of screening processes, ensuring the quality and safety of screening services, strengthening follow-up and support systems, and providing policy support and financial investment. The establishment of a comprehensive screening system often requires substantial investment in human, material, and financial resources, which can be challenging to achieve in regions with limited health care resources. Strengthening PP strategies can reduce the disease burden by targeting the cause, representing a more cost-effective and impactful approach. Establishing a comprehensive cancer PP service platform that integrates authoritative public education on malignant tumor PP, individualized malignant tumor risk assessment, and self-health management assistance accessible to the entire population will significantly enhance the overall effectiveness of CRC PP strategies.

Association of P53 Gene and Colorectal Cancer in Iran

Background: Colorectal cancer (CRC) is one of the leading causes of malignancies globally with a high mortality rate. Therefore, investigating the underlying mechanism and different risk factors contributing to this neoplasm is imperative, since P53 protein is a tumor suppressor protein, that has inhibiting effect on tumorigenesis, this study aims to assess the association of P53 gene and CRC within specific population, as geography is believed to be a risk factor for CRC. Materials and Methods: In this retrospective case-control study, 90 patients aged 18 years old and above, with CRC were enrolled. They were all scrutinized before and after their surgery. Data were extracted from their medical record, laboratory test results, standard questionnaire, imaging reports, physical exam, related symptoms and colonoscopy and biopsy reports. Data analysis was performed using SPSS software and the chi-square method. Results: 90 patients participated in this study, with the mean age of 71.57 years. There was no statistically significant association between age of patients and P53 mutation. Similarly, no correlation between any of the symptoms and P53 gene mutation was found. However, the risk of P53 mutation increased with larger tumor size (p&lt;0.021), deeper tissue invasion (p&lt;0.041) and higher levels of lymph node involvement (p&lt;0.031). Conclusion: this study investigates the relationship between P53 mutation and various clinical and pathological parameters. A significant association was observed between P53 mutation and tumor characteristics, including larger tumor size, deeper tissue invasion, and increased lymph node involvement. These findings suggest that P53 mutation may serve as a potential biomarker for assessing tumor aggressiveness and prognosis in colorectal cancer

Exploring the influence of anemia and inflammation indices on colorectal cancer: analysis of the national health and nutrition examination survey From 2011 to 2018.

Patients with colorectal cancer (CRC) frequently present with anemia and signs of infection. However, the relationships between these factors remain unclear. This study investigated the potential association between anemia, inflammatory indices, and CRC. We analyzed data from the 2011-2018 National Health and Nutrition Examination Survey to investigate links between anemia, inflammation, and CRC. Inflammatory indices, including the neutrophil-percentage-to-albumin ratio, neutrophil-to-lymphocyte ratio, and eosinophil-to-lymphocyte ratio, were analyzed. Following rigorous inclusion criteria, 14,114 participants were included. Statistical methods such as logistic regression and subgroup analyses were employed. Moreover, survival analysis was performed. Among the 14,114 participants, 0.6% had CRC and 11.0% were diagnosed with anemia. Anemia and inflammatory indices were associated with CRC, suggesting an increased risk (OR range: 2.03-2.50, P<0.05). Patients with CRC had lower red blood cell counts, reduced hemoglobin levels, and higher inflammatory indices. This is accompanied by an increase in the inflammatory indices, which is also a risk factor for CRC (OR range: 1.12-7.00, P<0.05). Survival analyses indicated that anemia was associated with lower survival rates, impacting all-cause, cancer, and CRC mortality. Our results indicate that anemia and inflammatory indices are correlated with CRC. Patients with CRC tend to exhibit increased inflammatory indices and decreased red blood cell count and albumin levels, potentially impacting survival.

From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma-carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.

Impact of Ascending HPV Infection on Colorectal Cancer Risk: Evidence from a Nationwide Study.

Colorectal cancer (CRC) is a prevalent and escalating health issue in Taiwan. This nationwide study delves into the relationship between Human Papillomavirus (HPV) infection and CRC risk, employing population datasets from 2007 to 2017. Cox regression analyses revealed a statistically significant hazard ratio (HR) of 1.73 (95% CI: 1.63-1.83) for CRC in HPV-positive patients, indicating a considerably elevated risk compared to non-infected individuals. Further, stratification by sex showed males with HPV have a higher CRC risk (HR = 1.49, 95% CI: 1.40-1.58) compared to females. Age-related analysis uncovered a progressive increase in CRC risk with advancing age (HR = 34.69 for over 80 years). The study of specific CRC subtypes showed varying risks: HR = 1.74 for the colon, HR = 1.64 for the rectum, and a notably higher HR = 4.72 for the anus. Comorbid conditions such as hypertension (HR = 1.26), diabetes mellitus (HR = 1.32), and abnormal liver function (HR = 1.18) also correlate with significantly increased CRC risks. These findings suggest that HPV is a significant risk factor for CRC, with disparities in risk based on anatomical location, demographic characteristics, and comorbidities, highlighting the need for intervention strategies and targeted prevention.

Comparison analysis of the burden and attributable risk factors of early-onset and late-onset colorectal cancer in China from 1990 to 2019.

The project intended to analyze the impact of burden and related risk factors of late-onset colorectal cancer (LOCRC) and early-onset colorectal cancer (EOCRC) in China, thus offering essential references for optimizing prevention and control strategies. Global Burden of Disease Study was employed to describe burden changes of EOCRC and LOCRC in China during 1990-2019, containing the numbers of incidence, deaths, prevalence, and disability-adjusted life years (DALYs), and to compare attributable deaths and DALYs risk factors in varying age and sex segments. The numbers and corresponding crude rates of incidence, deaths, prevalence, and DALYs of EOCRC and LOCRC in China during 1990-2019 demonstrated an upward trend across all age categories, with males being dramatically predominant. Overall, over time, the impact of a low-calcium diet and a low-fiber diet on mortality and DALY rates decreased, while the impact of other risk factors increased. In terms of gender, the risk factors affecting males changed greatly, with smoking, inadequate milk intake, and the low whole-grain diet being the main factors in 2019, while in 1990, the main factors were the low-calcium diet, smoking, and inadequate milk intake. The burden of colorectal cancer in China is concerning. Patients grouped by diagnostic age exhibit different characteristics, indicating the need for high-quality research in the future to achieve personalized medicine tailored to different population characteristics.

Role of Vitamin D Receptor (BsmI-VDR) and Insulin Receptor (NsiI-A/G) Gene Polymorphisms in Colorectal Adenoma Susceptibility.

Vitamin D deficiency and type 2 diabetes mellitus are risk factors for colorectal cancer, suggesting a role for vitamin D receptor (VDR) and insulin receptor (INSR) gene polymorphisms. We investigated the prevalence of the VDR-BsmI (rs1544410) and NsiI A/G-INSR (rs2059806) polymorphisms and their associations with colorectal adenoma (CRA) in a Romanian population. A case-control study was conducted with 110 participants (67 with CRA and 43 controls) who underwent colonoscopy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genotype and allele frequencies of the two polymorphisms. Regarding rs1544410 and CRA patients, genotype distribution was 35% B/B, 47% B/b, and 19% b/b. In the controls, the distribution was 21% B/B, 45% B/b, and 34% b/b. For rs2059806, 12% of CRA patients had A/A, 30% A/G, and 58% G/G, while 8% of the controls had A/A, 40% A/G, and 52% G/G. The recessive model showed an odds ratio of 2.84 (95% CI: 1.04-7.72, p = 0.033) for the b/b genotype. CRA patients with b/b or G/G genotypes were diagnosed at a younger age. The b allele of the rs1544410 was a risk factor for CRA. Patients with the b/b and G/G genotypes were diagnosed earlier.

Obesity-Associated Colorectal Cancer.

Colorectal cancer (CRC) affects approximately 2 million people worldwide. Obesity is the major risk factor for CRC. In addition, obesity contributes to a chronic inflammatory stage that enhances tumor progression through the secretion of proinflammatory cytokines. In addition to an increased inflammatory response, obesity-associated cancer presents accrued molecular factors related to cancer characteristics, such as genome instability, sustained cell proliferation, telomere dysfunctions, angiogenesis, and microbial alteration, among others. Despite the evidence accumulated over the last few years, the treatments for obesity-associated CRC do not differ from the CRC treatments in normal-weight individuals. In this review, we summarize the current knowledge on obesity-associated cancer, including its epidemiology, risk factors, molecular factors, and current treatments. Finally, we enumerate possible new therapeutic targets that may improve the conditions of obese CRC patients. Obesity is key for the development of CRC, and treatments resulting in the reversal of obesity should be considered as a strategy for improving antineoplastic CRC therapies.

Race adjustments in clinical algorithms can help correct for racial disparities in data quality

Despite ethical and historical arguments for removing race from clinical algorithms, the consequences of removal remain unclear. Here, we highlight a largely undiscussed consideration in this debate: varying data quality of input features across race groups. For example, family history of cancer is an essential predictor in cancer risk prediction algorithms but is less reliably documented for Black participants and may therefore be less predictive of cancer outcomes. Using data from the Southern Community Cohort Study, we assessed whether race adjustments could allow risk prediction models to capture varying data quality by race, focusing on colorectal cancer risk prediction. We analyzed 77,836 adults with no history of colorectal cancer at baseline. The predictive value of self-reported family history was greater for White participants than for Black participants. We compared two cancer risk prediction algorithms-a race-blind algorithm which included standard colorectal cancer risk factors but not race, and a race-adjusted algorithm which additionally included race. Relative to the race-blind algorithm, the race-adjusted algorithm improved predictive performance, as measured by goodness of fit in a likelihood ratio test (P-value: <0.001) and area under the receiving operating characteristic curve among Black participants (P-value: 0.006). Because the race-blind algorithm underpredicted risk for Black participants, the race-adjusted algorithm increased the fraction of Black participants among the predicted high-risk group, potentially increasing access to screening. More broadly, this study shows that race adjustments may be beneficial when the data quality of key predictors in clinical algorithms differs by race group.

Red and Processed Meat Intake, Polygenic Risk and the Prevalence of Colorectal Neoplasms: Results from a Screening Colonoscopy Population.

High red and processed meat intake and genetic predisposition are risk factors of colorectal cancer (CRC). However, evidence of their independent and joint associations on the risk of colorectal neoplasms is limited. We assessed these associations among 4774 men and women undergoing screening colonoscopy. Polygenic risk scores (PRSs) were calculated based on 140 loci related to CRC. We used multiple logistic regression models to evaluate the associations of red and processed meat intake and PRS with the risk of colorectal neoplasms. Adjusted odds ratios (aORs) were translated to genetic risk equivalents (GREs) to compare the strength of the associations with colorectal neoplasm risk of both factors. Compared to ≤1 time/week, processed meat intake >1 time/week was associated with a significantly increased risk of colorectal neoplasm [aOR (95% CI): 1.28 (1.12-1.46)]. This risk increase was equivalent to the risk increase associated with a 19 percentile higher PRS. The association of red meat intake with colorectal neoplasm was weaker and did not reach statistical significance. High processed meat intake and PRS contribute to colorectal neoplasm risk independently. Limiting processed meat intake may offset a substantial proportion of the genetically increased risk of colorectal neoplasms.

Sexual dimorphism of colorectal cancer in humans and colorectal tumors in a murine model.

In colorectal cancer, men exhibit a higher incidence than women, and there is a disturbance in the levels of sex steroids in serum in patients with this disease. Consistently, in animals, males have greater tumor growth than females in diverse models. Nevertheless, the role of sex steroids is not well established. For that, we analyzed the effect of the principal gonadal sex steroids in both sexes. We determined sex as a statistically risk factor for colorectal cancer with data obtained from GLOBOCAN database. To induce colorectal tumors, we used the gold standard chemical method of azoxymethane and dextran sulphate of sodium. To evaluate the role of sex steroids, we gonadectomized independent males and female animals, reconstituting and substituting them with 17β estradiol and dihydrotestosterone. Finally, we determined, in vitro, the proliferation of a human cell line exposed to 17β estradiol, testosterone, or dihydrotestosterone. Sex, as a risk factor for colorectal cancer, showed a statistically significant susceptibility of men over 50 years old. In vivo, males develop a greater number of tumors and with a larger size than females. In males, orchiectomy prevents tumor growth, whereas in females, ovariectomy promotes the development of neoplasms. DHT acts as a protumoral agent in both sexes. 17β estradiol reduces tumor growth in females but enhances it in males, showing a dimorphic effect. In vitro studies reveal that estradiol decreases the proliferation of the HCT-116 colon cancer cell line, while testosterone boosts proliferation in these cells. Interestingly, dihydrotestosterone does not influence proliferation.