Increased Risk Of Colorectal Cancer Research Articles

Understanding Lifestyle Choices That Increase Colorectal Cancer Risk

Understanding Lifestyle Choices That Increase Colorectal Cancer Risk

Colorectal cancer prognosis based on dietary pattern using synthetic minority oversampling technique with K-nearest neighbors approach

Generally, a person’s life span depends on their food consumption because it may cause deadly diseases like colorectal cancer (CRC). In 2020, colorectal cancer accounted for one million fatalities globally, representing 10% of all cancer casualties. 76,679 males and 78,213 females over the age of 59 from ten states in the United States participated in this analysis. During follow-up, 1378 men and 981 women were diagnosed with colon cancer. This prospective cohort study used 231 food items and their variants as input features to identify CRC patients. Before labelling any foods as colorectal cancer-causing foods, it is ethical to analyse facts like how many grams of food should be consumed daily and how many times a week. This research examines five classification algorithms on real-time datasets: K-Nearest Neighbour (KNN), Decision Tree (DT), Random Forest (RF), Logistic Regression with Classifier Chain (LRCC), and Logistic Regression with Label Powerset (LRLC). Then, the SMOTE algorithm is applied to deal with and identify imbalances in the data. Our study shows that eating more than 10 g/d of low-fat butter in bread (RR 1.99, CI 0.91–4.39) and more than twice a week (RR 1.49, CI 0.93–2.38) increases CRC risk. Concerning beef, eating in excess of 74 g of beef steak daily (RR 0.88, CI 0.50–1.55) and having it more than once a week (RR 0.88, CI 0.62–1.23) decreases the risk of CRC, respectively. While eating beef and dairy products in a daily diet should be cautious about quantity. Consuming those items in moderation on a regular basis will protect us against CRC risk. Meanwhile, a high intake of poultry (RR 0.2, CI 0.05–0.81), fish (RR 0.82, CI 0.31–2.16), and pork (RR 0.67, CI 0.17–2.65) consumption negatively correlates to CRC hazards.

Integrative analysis of causal associations between neurodegenerative diseases and colorectal cancer

BackgroundObservational studies have shown that the correlation between neurodegenerative diseases and colorectal cancer (CRC) remains controversial. Therefore, this study aimed to verify the causal association between these two diseases. MethodsMendelian randomization (MR) analysis was used to assess the causal relationships between five major neurodegenerative diseases and CRC. Multivariable MR (MVMR) analysis was conducted to assess the direct causal effect of neurodegenerative diseases on CRC. Colocalization and pathway enrichment analyses were conducted to further elucidate our results. Sensitivity analysis was conducted to assess the robustness of the results. ResultsGenetically predicted Alzheimer's disease (AD) nominally increased CRC risk (OR = 1.0620, 95%CI = 1.0127–1.1136, P = 0.013). There was no causal effect of genetically predicted CRC on neurodegenerative diseases. Furthermore, we demonstrated that genetically predicted AD marginally increased colon cancer risk (OR = 1.1621, 95%CI = 1.0267–1.3153, P = 0.017). Genetically predicted Lewy body dementia (LBD) had a significant causal effect on the increasing risk of colon cancer (IVW OR = 1.1779, 95%CI = 1.0694–1.2975, P = 0.001). MVMR indicated that effect of AD on colon cancer was driven by LBD, type 2 diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol (TC), processed meat consumption, smoking, alcohol consumption, and educational attainment, whereas the effect of LBD on colon cancer was only influenced by TC. Colocalization and pathway enrichment analysis suggested that LBD and colon cancer possibly shared causal variants (nearby gene APOE), and ERBB4 signaling and lipid metabolism may mediate the causal association between LBD and colon cancer. Sensitivity analysis confirmed the reliability of our findings. ConclusionsOur study demonstrated that genetic vulnerabilities to AD nominally increased the overall risk of CRC and colon cancer. Genetically predicted LBD indicated an elevated risk of colon cancer, potentially linked to ERBB4 signaling and lipid metabolism.

Income dynamics and risk of colorectal cancer in individuals with type 2 diabetes: a nationwide population-based cohort study.

Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D. Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HRn=5years vs. n=0years 1.11, 95% CI 1.04-1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HRn=5years vs. n=0years 0.81, 95% CI 0.73-0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

The association between ambient air pollution and colorectal cancer: a Mendelian randomization study

ABSTRACT Mounting epidemiology studies have reported the potential associations between ambient air pollution exposure and colorectal cancer (CRC). However, the genetic association between ambient air pollution and CRC remains unclear. Using the Genome-wide association study (GWAS) data from UK biobank, we explored the genetic association of CRC (5,657 cases and 372,016 controls) with four ambient air pollutants (PM2.5, PM10, NO2, NOx; n = 423,796 to 456,380) under the framework of Mendelian randomization (MR). Our results revealed a significant association between long-term NO2 exposure (per 10 µg/m3) and increased CRC risk, with an odds ratio (OR) of 1.02 (95% confidence interval [CI]: 1.00–1.03), while no statistical association was found between CRC risk and the other air pollutants. Sensitivity analysis confirmed the robustness of the results. It is imperative to consider the impact of air pollution, particularly NO2, in mitigating the risk of CRC.

Genetic Evidence for a Causal Relationship Between Innate Leukocytes and the Risk of Digestive System Cancers in East Asians and Europeans.

Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

Mexican physicians' knowledge and attitudes towards hereditary colorectal cancer risk management.

e22552 Background: Genetic cancer risk assessment (GCRA) has become an integral component of the management of patients with colorectal cancer (CRC). Understanding clinical criteria and interpreting screening tests to identify patients who should be prioritized for genetic testing is especially critical in resource-constrained settings such as Mexico, where access to genetic testing is limited. Methods: We designed a self-applicable survey consisting of 18 items, divided into three sections: 7 on knowledge, 5 on clinical approaches, and 6 on access to genetic testing. The aim was to assess the practice patterns of Mexican physicians in contact with patients at risk for hereditary CRC. Initially, the survey was piloted among oncology fellows to refine and improve its relevance and applicability. Following adjustments, it was disseminated using a QR code at the annual meeting of the Mexican Society of Oncology (SMeO) in September 2023. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. Results: A total of 78 physicians completed the survey, with a median age of 37 years (range, 27-70). Among them, 47.2% were female, 82% were medical oncologists, with a median practice duration of 6 years (range, 1- 40). 52.6% practice in cancer community centers, 83.4% were employed in public primary care settings, and 60% were affiliated to academic centers. Referral criteria for GCRA was identified correctly in 66.7% who recognized age at CRC diagnosis &lt; 50 years, 57.7% synchronous or metachronous CRC, 50% deficient mismatch repair CRC, and 37.2% PREMM5 score of ≥2.5%. Lynch syndrome, Familial Adenomatous Polyposis (FAP), and Cowden syndrome were identified as syndromes with an increased CRC risk by 76.9%, 71.8% and 56.7% of respondents, respectively. Decision-making based on likely pathogenic and pathogenic variants was indicated by 26.9% and 69.2%, while 12.8% reported making decisions based on variants of uncertain significance (VUS). Regarding clinical approach, 74.4% inquired about a family history of cancer at the initial consultation, and 66.7% referred patients for genetic counseling. The primary obstacles to accessing GCRA were the cost of genetic testing (43.6%) and the absence of medical genetics services at their centers (39.7%). Only 23% reported the availability of cascade testing within their practice. Conclusions: The identification of patients at risk of hereditary CRC was suboptimal among Mexican physicians. A high proportion of respondents were not fully qualified to interpret correctly genetic testing results. These indicate a need for awareness and educational programs to improve providers’ knowledge on predisposition cancer syndromes.

The association of the killer cell immunoglobulin-like receptor (KIR) genotype distribution and HLA-C ligands in colorectal cancer in the eastern region of Saudi Arabia

Colorectal cancer (CRC) is the most common cause of cancer-related mortality globally. It ranks as the most common cancer among men and the third most prevalent among women in Saudi Arabia, especially in the eastern region. The immune system's response to cancer is significantly influenced by natural killer cells through their killer-cell immunoglobulin-like receptors (KIRs) interaction with human leukocyte antigen (HLA) molecules. Our research aimed to target a homogeneous ethnic group in the eastern region of Saudi Arabia, analyzing the distribution of 16 KIR genes and HLA-C1/C2 allotypes in 50 CRC patients and 63 healthy controls using the sequence-specific PCR amplification method. Findings revealed significantly lower frequencies of the 2DL2 and 3DL1 genes in CRC patients compared to controls (OR = 2.21; P = 0.04) and (OR = 7.46; P = 0.00009), respectively. Additionally, a higher prevalence of HLA-C2 was noted in CRC patients (84 %) versus controls (66.7 %) (OR = 2.26; P = 0.04). Conversely, the HLA-C1C2 combination showed a protective effect against CRC (OR = 0.38; P = 0.04). Our combinatorial analysis further identified specific gene combinations correlating with CRC risk or protection. Notably, the absence of KIR2DL2 combined with the presence of KIR2DS2 emerged as a significant risk factor, while various combinations involving KIR2DL2 and/or KIR2DS1 with HLA-C ligands were associated with either increased susceptibility or protection. The study underscores the protective role of KIR2DL2 against CRC in Saudi Arabia's eastern region and suggests that the absence of KIR2DL2, especially when KIR2DS2 is present, might increase CRC risk. This research contributes to understanding genetic influences on CRC susceptibility, emphasizing the potential of KIR and HLA interactions as biomarkers for CRC risk assessment.

Impact of ambient air pollution on colorectal cancer risk and survival: insights from a prospective cohort and epigenetic Mendelian randomization study

This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations. In epigenetic two-sample Mendelian randomization analyses, we examine the associations between genetically predicted DNA methylation related to air pollution and CRC risk. Further genetic colocalization and gene-environment interaction analyses provided different insights to disentangle pathogenic effects of air pollution via epigenetic modification. During a median 12.97-year follow-up, 5767 incident CRC cases among 428,632 participants free of baseline CRC and 533 deaths in 2401 patients with CRC were documented in the UK Biobank. A higher APES score was associated with an increased CRC risk (HR, 1.03, 95% CI= 1.01-1.06; P=0.016) and poorer survival (HR, 1.13, 95% CI= 1.03-1.23; P=0.010), particularly among participants with insufficient physical activity and ever smokers (Pinteraction > 0.05). A subsequent meta-analysis of seven observational studies, including UK Biobank data, corroborated the association between PM2.5 exposure (per 10μg/m3 increment) and elevated CRC risk (RR,1.42, 95% CI= 1.12-1.79; P=0.004; I2=90.8%). Genetically predicted methylation at PM2.5-related CpG site cg13835894 near TMBIM1/PNKD and cg16235962 near CXCR5, and NO2-related cg16947394 near TMEM110 were associated with an increased CRC risk. Gene-environment interaction analysis confirmed the epigenetic modification of aforementioned CpG sites with CRC risk and survival. Our study suggests the association between air pollution and CRC incidence and survival, underscoring the possible modifying roles of epigenomic factors. Methylation may partly mediate pathogenic effects of air pollution on CRC, with annotation to epigenetic alterations in protein-coding genes TMBIM1/PNKD, CXCR5 and TMEM110. Xue Li is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), the National Nature Science Foundation of China (No. 82204019) and Healthy Zhejiang One Million People Cohort (K-20230085). ET is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804). MGD is supported by the MRC Human Genetics Unit Centre Grant (U127527198).

Modifiable Risk Factors and Risk of Colorectal and Endometrial Cancers in Lynch Syndrome: A Systematic Review and Meta-Analysis.

Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied in Lynch syndrome. Searches were conducted on MEDLINE, Embase, and Web of Science for cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Adjusted hazard ratios (HRs) and 95% CIs for colorectal and endometrial cancers were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462), and the meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. A total of 770 citations were reviewed. Eighteen studies were identified for qualitative synthesis, with seven colorectal cancer (CRC) studies eligible for meta-analysis. Obesity (HR, 2.38 [95% CI, 1.52 to 3.73]) was associated with increased CRC risk. There was no increased CRC risk associated with smoking (HR, 1.04 [95% CI, 0.82 to 1.32]) or alcohol intake (HR, 1.32 [95% CI, 0.97 to 1.81]). Type 2 diabetes mellitus (T2DM) and some dietary factors might increase risk of CRC although more studies are needed. In a qualitative synthesis of three endometrial cancer cohort studies, female hormonal risk factors and T2DM may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Lifestyle recommendations related to weight and physical activity may also be relevant to cancer prevention for individuals with Lynch syndrome. Further high-quality prospective cohort studies, in particular, including endometrial cancer as an end point, are needed to inform evidence-based cancer prevention strategies in this high-risk population.

Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk

We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

Effects of Helicobacter pylori infection on intestinal microbiota, immunity and colorectal cancer risk.

Infecting about half of the world´s population, Helicobacter pylori is one of the most prevalent bacterial infections worldwide and the strongest known risk factor for gastric cancer. Although H. pylori colonizes exclusively the gastric epithelium, the infection has also been associated with various extragastric diseases, including colorectal cancer (CRC). Epidemiological studies reported an almost two-fold increased risk for infected individuals to develop CRC, but only recently, direct causal and functional links between the chronic infection and CRC have been revealed. Besides modulating the host intestinal immune response, H. pylori is thought to increase CRC risk by inducing gut microbiota alterations. It is known that H. pylori infection not only impacts the gastric microbiota at the site of infection but also leads to changes in bacterial colonization in the distal large intestine. Considering that the gut microbiome plays a driving role in CRC, H. pylori infection emerges as a key factor responsible for promoting changes in microbiome signatures that could contribute to tumor development. Within this review, we want to focus on the interplay between H. pylori infection, changes in the intestinal microbiota, and intestinal immunity. In addition, the effects of H. pylori antibiotic eradication therapy will be discussed.

Comparing the Associations of Dietary Patterns Identified through Principal Component Analysis and Cluster Analysis with Colorectal Cancer Risk: A Large Case-Control Study in China.

Examining the association between dietary patterns and colorectal cancer (CRC) risk can provide valuable insights beyond the assessment of individual foods or nutrients. However, there is a lack of in-depth analysis of dietary patterns and CRC risk in Chinese populations, and few studies have compared dietary patterns derived from different posteriori methods with the aim of predicting disease risk. The aim of this study was to derive dietary patterns using both principal component analysis (PCA) and cluster analysis (CA) and to assess their respective associations with CRC risk. A large-scale case-control study was conducted in Guangdong Province, China, including 2799 incident colorectal cancer cases and an equal number of frequency-matched controls. Dietary intake information was gathered through the use of a validated food frequency questionnaire. PCA and CA were used to derive dietary patterns. A multivariable logistic regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). Four major dietary patterns were identified by PCA. CA identified two dietary patterns, referred to as the "Balanced dietary pattern" and the "Refined grain dietary pattern". Notably, there were significant inverse associations between the milk-egg-nut-soy dietary pattern (aOR, 0.51; 95% CI, 0.42, 0.62), the vegetable-fruit dietary pattern (aOR, 0.61; 95%CI, 0.51, 0.74), and the poultry-fish dietary pattern (aOR, 0.81; 95%CI, 0.68, 0.97) and CRC risk. However, the red meat-preserved food dietary pattern was associated with an increased risk of CRC (aOR, 2.99; 95%CI, 2.43, 3.67). When compared with the Refined grain dietary pattern, the Balanced dietary pattern showed a decreased risk of CRC (aOR, 0.59; 95%CI, 0.52, 0.66). The results from the comparison of the two methods indicate that both CA and PCA derived remarkably similar patterns. The combined use of PCA and CA identified consistent underlying patterns, showing comparable associations with CRC risk. These findings suggest that individuals who prefer dietary patterns characterized by a high intake of red meat, preserved food, and refined grains should be cautious about their increased CRC risk. Conversely, dietary patterns rich in fruits, vegetables, and high-quality protein sources are advisable for the prevention of CRC in the Chinese population.

The gut microbiota in adults with cystic fibrosis compared to colorectal cancer

BackgroundGut dysbiosis is implicated in colorectal cancer (CRC) pathogenesis. Cystic fibrosis (CF) is associated with both gut dysbiosis and increased CRC risk. We therefore compared the faecal microbiota from individuals with CF to CRC and screening samples. We also assessed changes in CRC-associated taxa before and after triple CF transmembrane conductance regulator (CFTR) modulator therapy. MethodsBacterial DNA amplification comprising V4 16S rRNA analysis was conducted on 84 baseline and 53 matched follow-up stool samples from adults with CF. These data were compared to an existing cohort of 430 CRC and 491 control gFOBT samples from the NHS Bowel Cancer Screening Programme. Data were also compared to 26 previously identified CRC-associated taxa from a published meta-analysis. ResultsFaecal CF samples had a lower alpha diversity and clustered distinctly from both CRC and control samples, with no clear clinical variables explaining the variation. Compared to controls, CF samples had an increased relative abundance in 6 of the 20 enriched CRC-associated taxa and depletion of 2 of the 6 taxa which have been reported as reduced in CRC. Commencing triple modulator therapy had subtle influence on the relative abundance of CRC-associated microbiota (n = 23 paired CF samples). ConclusionsCF stool samples were clearly dysbiotic, clustering distinctly from both CRC and control samples. Several bacterial shifts in CF samples resembled those observed in CRC. Studies assessing the impact of dietary or other interventions and the longer-term use of CFTR modulators on reducing this potentially pro-oncogenic milieu are needed.

Abstract B143: Temporal trends in colorectal cancer mortality in the five regions of Georgia, 1975-2018: A Joinpoint regression analyses

Abstract Background: Colorectal cancer (CRC) is the third leading cause of death in Georgia. There remain significantly higher CRC mortality rates in the five public health regions of Georgia (Clayton, West Central, East Central, Southeast, and Northeast regions) in comparison to the rates in the State of Georgia. However, studies that examined temporal trends in CRC mortality rates in small geographic regions are still limited. The aim of this study was to analyze the time trends in mortality due to CRC within five regions of Georgia, stratified by age groups to assess any changes in mortality trends for the period 1975 -2018. Methods: Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database: Mortality - All COD, Aggregated with County, Total U.S. were used to select 1975-2018 CRC mortality data. We conducted Joinpoint regression analyses of the trends in age-adjusted mortality rates (ADMRs) due to CRC, stratified by the five regions of Georgia. Age differences in mortality were also examined. The average annual percent change (AAPC) and annual percent change (APC) with confidence intervals of 95% were calculated. Results: A total of 12,972 deaths from CRC were reported in these five regions during the period 1975-2018. The ADMR of CRC were 24.4, 24.9, 23.4, 22.7, and 25.7 per 100,000 in Clayton, East Central, Southeast, Northeast, and West Central regions, respectively. The mortality rates for CRC decreased from 1975 to 2018 in Clayton, Northeast, and Southeast regions (AAPC: -1.7% to -3.4%, p-value&amp;lt;0.05). One Joinpoint trend found a significant reduction in mortality in the East Central (1984-2018) (APC: -4.1%, p-value&amp;lt;0.001) and West Central (1981-2018) regions (APC: -3.2%, p-value=0.003). When examining age differences, patients aged 75 years or older had a significant decrease in mortality from 1975 to 2018 except in the East Central region (AAPC: -2.4% to -4.5%, p-value&amp;lt;0.05). In the East Central region, one Joinpoint demonstrated a significant decrease in mortality during 1987-2018 for the 60-74 age group and during 1984 -2018 for 75+ age group (APC: -5.1% &amp; -6.1%, respectively; both p-value&amp;lt;0.05). Reduced mortality rates were also found from 1984 to 2018 in the 60-74 age group in the Northeast region (APC: -4.3%, p-value&amp;lt;0.001). However, Northeast Georgians aged 15-59 years demonstrated a non-significant trend for increase in mortality from 1975 to 2018 (AAPC: 2.1%, p-value=0.181). Conclusion: The regional burden of colorectal cancer varied across the five regions of Georgia with CRC mortality rates decreased significantly in the Clayton, Northeast, and Southeast regions. Although reduced mortality rates were found in older patients in most regions, younger patients living in Northeast regions demonstrated a slight increase in mortality. Increased CRC risk awareness, culturally tailored prevention strategies through timely CRC screening uptake, and improved access to cancer treatment are extremely important to reduce the CRC burden, especially in the most affected regions in Georgia. Citation Format: Meng-Han Tsai, Daramola N. Cabral, Justin X. Moore, Jorge Cortes. Temporal trends in colorectal cancer mortality in the five regions of Georgia, 1975-2018: A Joinpoint regression analyses [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B143.

Diet-Wide Association, Genetic Susceptibility and Colorectal Cancer Risk: A Prospective Cohort Study.

Both genetic and dietary factors play significant roles in the etiology of colorectal cancer (CRC). To evaluate the relationship between certain food exposures and the risk of CRC, we carried out a large-scale association analysis in the UK Biobank. The associations of 139 foods and nutrients' intake with CRC risk were assessed among 118,210 participants. A polygenic risk score (PRS) of CRC was created to explore any interaction between dietary factors and genetic susceptibility in CRC risk. The hazard ratio (HR) and 95% confidence interval (CI) of CRC risk linked to dietary variables and PRS were estimated using Cox regression models. Multiple comparisons were corrected using the error discovery rate (FDR). During a mean follow-up of 12.8 years, 1466 incidents of CRC were identified. In the UK Biobank, alcohol and white bread were associated with increased CRC risk, and their HRs were 1.08 (95% CI: 1.03-1.14; FDRP = 0.028) and 1.10 (95% CI: 1.05-1.16; FDRP = 0.003), whereas dietary fiber, calcium, magnesium, phosphorus, and manganese intakes were inversely associated. We found no evidence of any PRS-nutrient interaction relationship in relation to CRC risk. Our results show that higher intakes of alcohol and white bread are associated with increased CRC risk, whilst dietary fiber, calcium, magnesium, phosphorus, and manganese are inversely associated.

Type 2 Diabetes and Colorectal Cancer Risk

ImportanceType 2 diabetes and colorectal cancer (CRC) disproportionately burden indviduals of low socioeconomic status and African American race. Although diabetes is an emerging CRC risk factor, associations between diabetes and CRC in these populations are understudied.ObjectiveTo determine if diabetes is associated with CRC risk in a cohort representing understudied populations.Design, Setting, and ParticipantsThis cohort study uses data from the prospective Southern Community Cohort Study in the US, which recruited from 2002 to 2009 and completed 3 follow-up surveys by 2018. Of about 85 000 participants, 86% enrolled at community health centers, while 14% were enrolled via mail or telephone from the same 12 recruitment states. Participants with less than 2 years of follow-up, previous cancer diagnosis (excluding nonmelanoma skin cancer) at enrollment, missing enrollment diabetes status, diabetes diagnosis before age 30, and without diabetes at enrollment with no follow-up participation were excluded. Data were analyzed from January to September 2023.ExposuresPhysician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups.Main Outcomes and MeasuresDiabetes diagnosis was hypothesized to be positively associated with CRC risk before analysis. Incident CRC was assessed via state cancer registry and National Death Index linkage. Hazard ratios and 95% CIs were obtained via Cox proportional hazard models, using time-varying diabetes exposure.ResultsAmong 54 597 participants, the median (IQR) enrollment age was 51 (46-58) years, 34 786 (64%) were female, 36 170 (66%) were African American, and 28 792 (53%) had income less than $15 000 per year. In total, 289 of 25 992 participants with diabetes developed CRC, vs 197 of 28 605 participants without diabetes. Diabetes was associated with increased CRC risk (hazard ratio [HR], 1.47; 95% CI, 1.21-1.79). Greater associations were observed among participants without colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and with smoking history (HR, 1.62; 95% CI, 1.14-2.31), potentially due to cancer screening differences. Greater associations were also observed for participants with recent diabetes diagnoses (diabetes duration &amp;amp;lt;5 years compared with 5-10 years; HR, 2.55; 95% CI, 1.77-3.67), possibly due to recent screening.Conclusions and RelevanceIn this study where the majority of participants were African American with low socioeconomic status, diabetes was associated with elevated CRC risk, suggesting that diabetes prevention and control may reduce CRC disparities. The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening.

A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.

Transcriptome-wide association studies (TWAS) have identified many putative susceptibility genes for colorectal cancer (CRC) risk. However, susceptibility miRNAs, critical dysregulators of gene expression, remain unexplored. We genotyped DNA samples from 313 CRC East Asian patients and performed small RNA sequencing in their normal colon tissues distant from tumors to build genetic models for predicting miRNA expression. We applied these models and data from genome-wide association studies (GWAS) including 23 942 cases and 217 267 controls of East Asian ancestry to investigate associations of predicted miRNA expression with CRC risk. Perturbation experiments separately by promoting and inhibiting miRNAs expressions and further in vitro assays in both SW480 and HCT116 cells were conducted. At a Bonferroni-corrected threshold of P < 4.5 × 10-4, we identified two putative susceptibility miRNAs, miR-1307-5p and miR-192-3p, located in regions more than 500kb away from any GWAS-identified risk variants in CRC. We observed that a high predicted expression of miR-1307-5p was associated with increased CRC risk, while a low predicted expression of miR-192-3p was associated with increased CRC risk. Our experimental results further provide strong evidence of their susceptible roles by showing that miR-1307-5p and miR-192-3p play a regulatory role, respectively, in promoting and inhibiting CRC cell proliferation, migration, and invasion, which was consistently observed in both SW480 and HCT116 cells. Our study provides additional insights into the biological mechanisms underlying CRC development.

Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank

BackgroundThis study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk.MethodsWe analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term.ResultsDuring a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05–1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18–1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97–2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08–1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00–1.19 for low vs. high WCRF dietary scores).ConclusionDietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

Knowledge and Attitude of Inflammatory Bowel Disease Patients Toward Colorectal Cancer Risk, Its Management, and the Role of Healthcare Providers: A Cross-Sectional Study in the UK.

Inflammatory bowel disease (IBD) increases the risk for colorectal cancer (CRC). Limited literature exists on patients' knowledge of CRC risk and management. Attitude toward doctor-recommended management and the role of healthcare providers (HCPs) in CRC risk awareness remain unexplored. This study aimed to fill the gap in knowledge about CRC risk awareness and management in IBD patients in the UK. This cross-sectional internet-based study was conducted in April-July 2019. Adult (>18 years) IBD patients with a confirmed diagnosis for 2 years and adequate command of English language were invited from non-Natinal Health Services sources. A self-designed and piloted questionnaire with open- and closed-ended questions was used. Closed-ended data were analyzed using descriptive statistics and open-ended responses were analyzed using content analysis. Ninety-two participants (52.5% Crohn's disease and 67.5% females) responded. Around 88% knew that IBD increased CRC risk. Only 20.7% were aware of colonoscopy as the best screening tool; 88% were unaware of screening initiation time. Almost 90% would agree to a doctor's recommendation of colonoscopy. For dysplasia with 10% risk of CRC, 46.7% would not agree with colectomy. Some 48% reported to have never had a discussion about the risk of CRC in IBD with their HCPs, while 58% were not informed of the role of screening and surveillance in managing CRC risk. IBD patients were poorly aware of CRC risk management and had mixed willingness to comply with a doctor's recommendation. HCP's role in cancer knowledge dissemination was suboptimal and patients desired more information.