Risk Of Incident Colorectal Cancer Research Articles

Higher levels of neighborhood deprivation and risk for incident colorectal cancer and mortality outcomes: A systematic review and meta-analysis.

131 Background: Significant geographic and racial disparities exist for colorectal cancer (CRC) incidence and mortality in the United States (US), which may be caused by neighborhood-level deprivation and limited access to preventative cancer screening. We completed the first systematic review and meta-analysis of neighborhood-level deprivation in relation to CRC incidence, mortality, and screening among individuals from the US. Methods: A systematic literature review was completed to identify original research articles from PubMed, Scopus, and Web of Science. Eligible studies reported associations between deprivation at the census block or tract level using a validated deprivation index (e.g. the Area Deprivation Index or Yost Index) and CRC incidence, mortality, or screening outcomes in a US-based sample. A fixed-effects meta-analysis was completed using inverse-variance weighting to estimated hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for CRC incidence, mortality, and screening outcomes, comparing the highest vs. lowest quantiles of neighborhood-level deprivation. All analyses were completed using the meta package in R. Results: In total, 19 studies were included in the meta-analysis. Living in a neighborhood in the highest quantile of deprivation was associated with significantly higher risk for incident CRC (HR 1.37, 95% CI 1.34-1.41, seven studies). In stratified analysis, positive associations with incident CRC were observed for White (HR 1.43, 95% CI 1.39-1.47, three studies), Black (HR 1.18, 95% CI 0.96-1.44, three studies), and Asian/Pacific Islander individuals (HR 1.18, 95% CI 1.08-1.28, two studies). For individuals diagnosed with CRC, higher deprivation was associated with elevated risk for overall mortality (HR 1.11, 95% CI 1.10-1.13, four studies) and CRC-specific mortality (HR 1.17, 95% CI 1.15-1.19, seven studies). Higher deprivation was associated with lower completion of recommended screening for CRC, including colonoscopy, sigmoidoscopy, or fecal occult blood testing (OR 0.76, 95% CI 0.74-0.79, four studies). Conclusions: Individuals who reside in neighborhoods with high levels of deprivation have significantly elevated risk for CRC incidence and mortality compared to individuals from low deprivation neighborhoods. Targeting healthcare resources to highly deprived neighborhoods to increase uptake of preventative screening may help to address racial and geographic disparities for CRC.

Comparative analysis of GLP-1 receptor agonists versus metformin on cancer outcomes in patients with polycystic ovarian syndrome: A real-world multi-center cohort study in the United States.

402 Background: To compare the effects of GLP-1 receptor agonists (GLP1RA) versus metformin on incident cancer outcomes in the female polycystic ovarian syndrome (PCOS) population. Methods: This retrospective cohort study utilized electronic health records from over 50 U.S. healthcare organizations (TriNetX). The baseline cohort comprised females aged ≥ 18 with ≥ two prescriptions for GLP1 RAor metformin following a diagnosis of PCOS, between May 1, 2005 (first GLP1 RA approval date), and December 31, 2021. All cancer types were identified using ICD-10 codes. The index date was the initiation of GLP1RA or metformin. We performed a 1:1 propensity score matched based on demographics, comorbidities, socioeconomic factors, healthcare utilization, and biomarkers (HbA1c, LDL, HDL, triglycerides, and cholesterol), insulin use and PCOS medications before index date. Analysis was performed with intention-to-treat approach. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the comparison groups were calculated by the Cox regression model. Patients were followed and censored upon meeting any of the following criteria: development of an outcome, the study end date of May 19, 2024, or loss to follow-up, whichever occurred first. Results: A total of 8,223 pairs of GLP1RA initiators and metformin initiators were included. Compared to metformin, GLP1RA was associated with a lower risk of incident colorectal cancer (HR 0.35, 95% CI 0.22-0.57) and breast cancer (HR 0.55, 95% CI 0.39-0.78). There were no significant differences in risk between the GLP1RA group and metformin group for endometrial (HR 0.82, 95% CI 0.49-1.37), cervical (HR 1.17, 95% CI 0.64-2.12), ovarian (HR 1.09, 95% CI 0.56-2.11), respiratory (HR 0.32, 95% CI 0.17-0.60), skin (HR 0.51, 95% CI 0.37-0.69), kidney cancer(HR 0.99, 95% CI 0.33-3.06), thyroid cancer (HR 1.37, 95% CI 0.88-2.13), other endocrine (HR 0.81, 95% CI 0.15- 0.44), leukemia and lymphoma (HR 1.03, 95% CI 0.91-1.16), brain (HR 0.97, 95% CI 0.24-3.96), pancreatic cancer(HR 0.50, 95% CI 0.16-1.55), esophageal cancer (HR 1.99, 95% CI 0.24-16.18), stomach cancer (HR 0.33, 95% CI 0.07-1.47), and intrahepatic cancer (HR 0.89, 95% CI 0.40-1.99). Conclusions: GLP-1 receptor agonists were associated with a lower risk of colorectal and breast cancer compared to metformin in females with PCOS, with no significant differences in risk for other cancer types.Further investigation is necessary to verify the underlying therapeutic mechanisms.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia

The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Body mass index, calculated as weight in kilograms divided by height in meters squared. The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

The association between dietary folate intake and risk of colorectal cancer incidence: A systematic review and dose‒response meta-analysis of cohort studies

BackgroundDietary components can influence the incidence of colorectal cancer (CRC). Folate is one of the compounds that plays an essential role in the formation of DNA structures, which can lead to or prevent tumorigenesis. The present study is the first systematic review and dose–response meta-analysis of cohort studies evaluating the association between dietary folate intake and the risk of CRC. MethodsThe PubMed/Medline, Scopus, and ISI Web of Science databases were systematically searched for cohort studies that assessed the association between folate intake and CRC up to January 2024. Summary relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using a random effects model. Also, linear and nonlinear dose-response analyses were conducted for the dose-response associations between folate intake and risk of CRC. ResultsEighteen prospective cohort studies with 931,469 participants, 14,860 CRC patients, 3536 colon cancer (CC) patients, and 1075 rectal cancer (RC) patients were included in the analysis. The summary RR of CRC for each 100-μg increase in dietary folate intake was 0.97 (95 % CI: 0.95–0.99, I2: 0.0 %, P-heterogeneity: 0.616), which can be related to BMI (0.97 (95 % CI: 0.95–0.99)); a more protective effect was also observed in subjects who drank alcohol (0.97 (95 % CI: 0.95–0.99)) and those who smoked (0.97 (95 % CI: 0.95–0.99)). Additionally, it was positively related to a 7 % lower risk of CC (0.93 (95 % CI: 0.87–0.99, I2: 33.7 %, P-heterogeneity: 0.159)), and the null relation for RC was 0.98 (95 % CI: 0.90–1.08), I2: 16.6 %, P-heterogeneity: 0.309). There was evidence of nonlinearity in which up to 500 μg/day dietary folate intake was inversely associated with CC (P nonlinearity = 0.04). ConclusionThe findings showed an inverse association between dietary folate intake and the risk of CRC, especially in high-risk persons, those who have a higher BMI, alcohol drinkers, and smokers.

Duration of risk reduction in colorectal cancer incidence and mortality after a complete colonoscopy in Ontario, Canada: a population-based cohort study

Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy. We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality. 5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]). Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed. Canadian Institutes of Health Research.

Blood-Based Epigenetic Age Acceleration and Incident Colorectal Cancer Risk: Findings from a Population-Based Case-Control Study.

This study investigates the association between epigenetic age acceleration (EAA) derived from DNA methylation and the risk of incident colorectal cancer (CRC). We utilized data from a random population sample of 9,360 individuals (men and women, aged 45-69) from the HAPIEE Study who had been followed up for 16 years. A nested case-control design yielded 35 incident CRC cases and 354 matched controls. Six baseline epigenetic age (EA) measures (Horvath, Hannum, PhenoAge, Skin and Blood (SB), BLUP, and Elastic Net (EN)) were calculated along with their respective EAAs. After adjustment, the odds ratios (ORs) for CRC risk per decile increase in EAA ranged from 1.20 (95% CI: 1.04-1.39) to 1.44 (95% CI: 1.21-1.76) for the Horvath, Hannum, PhenoAge, and BLUP measures. Conversely, the SB and EN EAA measures showed borderline inverse associations with ORs of 0.86-0.87 (95% CI: 0.76-0.99). Tertile analysis reinforced a positive association between CRC risk and four EAA measures (Horvath, Hannum, PhenoAge, and BLUP) and a modest inverse relationship with EN EAA. Our findings from a prospective population-based-case-control study indicate a direct association between incident CRC and four markers of accelerated baseline epigenetic age. In contrast, two markers showed a negative association or no association. These results warrant further exploration in larger cohorts and may have implications for CRC risk assessment and prevention.

Abstract 4429: Plasma metabolic profiles in association with subsequent risk of colorectal cancer in the UK Biobank cohort

Abstract Background: Dysregulation of metabolic processes contributes to colorectal cancer (CRC) etiology. We aimed to comprehensively evaluate the prospective associations between pre-diagnostic metabolic biomarkers and CRC risk in 230,420 UK Biobank participants. Methods: A total of 249 metabolic biomarkers were measured by nuclear magnetic resonance spectroscopy from baseline plasma samples. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of metabolic biomarkers with CRC risk after adjusting for potential confounders. Subgroup analyses were performed by sex and CRC subsites (i.e., proximal colon, distal colon, rectum). We also conducted factor analyses to identify latent factors and examined their associations with CRC risk. Results: During a median follow-up time of 9.7 years, 2,410 incident primary CRC cases were identified after excluding participants diagnosed with CRC within two years after blood collection. After correcting for multiple testing, 50 metabolic biomarkers, including lipids and lipoproteins, fatty acids, ketone bodies, and inflammation, were significantly associated with incident CRC risk. No statistically significant differences were observed for the biomarker-CRC associations by sex and CRC subsite. In the sensitivity analysis, excluding cholesterol-lowering medication users did not alter the main findings. In factor analyses, we identified a significant association of CRC risk (HR = 1.08; 95% CI = 1.04-1.13; P-value = 6.89×10-5) with a metabolite pattern which was positively correlated with triglycerides and inversely correlated with relative concentrations of omega-6 fatty acids and polyunsaturated fatty acids. Conclusion: We identified multiple metabolic biomarkers and a metabolite pattern associated with CRC risk in a large prospective cohort. These findings suggest lipid metabolism may contribute to carcinogenesis of the colorectum. Citation Format: Fangcheng Yuan, Guochong Jia, Wanqing Wen, Wei Zheng. Plasma metabolic profiles in association with subsequent risk of colorectal cancer in the UK Biobank cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4429.

Metformin’s role in lowering colorectal cancer risk among individuals with diabetes from the Southern Community Cohort Study

BackgroundMetformin, utilized to manage hyperglycemia, has been linked to a reduced risk of colorectal cancer (CRC) among individuals with diabetes. However, evidence is lacking for non-Hispanic Black individuals and those with lower socioeconomic status (SES), who face elevated risk for both diabetes and CRC. In this study, we investigated the association between metformin use and incident CRC risk within the Southern Community Cohort Study (SCCS), a racially- and SES-diverse prospective cohort. MethodsParticipants reported their diabetes diagnosis and medications, including metformin, upon enrollment (2002–2009) and during follow-up surveys approximately every five years. Incident cases of CRC were identified through state cancer registries and the National Death Index. Proportional hazards models were employed to explore the relationship between metformin use and CRC risk, adjusted for cancer risk factors. ResultsA total of 25,992 participants with diabetes were included in the analysis, among whom 10,095 were taking metformin. Of these participants, 76% identified as non-Hispanic Black, and 60% reported household incomes <$15,000/year. Metformin use was associated with a significantly lower CRC risk (HR [95% CI]: 0.71 [0.55–0.93]), with consistent results for both colon (0.80 [0.59–1.07]) and rectal cancers (0.49 [0.28–0.86]). The protective association appeared to be stronger among non-Hispanic White individuals (0.51 [0.31–0.85]) compared to non-Hispanic Black participants (0.80 [0.59–1.08], p-interaction =.13). Additionally, a protective association was observed among obese individuals (BMI ≥30 kg/m2, 0.59 [0.43–0.82] but not among non-obese participants (0.99 [0.65–1.51], p-interaction =.05) ConclusionOur findings indicate that metformin use is associated with a reduced risk of CRC in individuals with diabetes, including among those from predominantly low SES backgrounds. These results support previous epidemiological findings, and demonstrate that the protective association for metformin in relation to incident CRC likely generalizes to populations with higher underlying risk.

The risk of colorectal cancer incidence in a cohort of individuals occupationally exposed to ionizing radiation

The increased risk of colorectal cancer following ionizing radiation exposure was demonstrated in a number of epidemiological studies. Earlier, no impact of occupational radiation exposure on colorectal cancer incidence or mortality was observed in a cohort of workers of the nuclear industrial facility, Mayak Production Association (PA). Extension of the follow-up of the cohort and improvement of dose estimates for personnel made it possible to update the earlier findings. The study objective is to assess the risk of colorectal cancer incidence associated with chronic occupational radiation exposure taking into account non-radiation factor effects. The study cohort included 22,377 workers employed at the reactor, plutonium-producing and radiochemical plants of Mayak PA (hiring period 1948–1982; follow-up period ended on December 31, 2018). Using the Poisson regression (EPICURE software), the relative risks (RRs with 95 % confidence intervals, (95 % CI)) of colorectal cancer incidence were estimated depending on the most significant non-radiation factors (sex, age, smoking, alcohol consumption, excessive body mass and obesity, intestinal polyps, chronic colitis). These values were also calculated for certain ranges of occupational exposure doses relying on data provided by ‘The Mayak Worker Dosimetry System – 2013’. The linear model was used to analyze the dose-response relationship. In the study cohort, the RR of colorectal cancer incidence was lower in females than in males: 0.72 (95 % CI: 0.55; 0.96) for colon and 0.48 (95 % CI: 0.34; 0.67) for rectum. The increased RR of the rectum cancer incidence was observed for cases with intestinal polyps: 3.42 (95 % CI: 1.68; 6.19). The colon cancer incidence risk increased with increasing age of workers, but other non-radiation factors were not shown to affect the results. This study supported the earlier results: no association was observed between the risk of colorectal cancer incidence and doses of occupational external gamma-ray or internal alpha-particle exposures.

Риск заболеваемости раком кишечника в когорте работников, подвергшихся хроническому профессиональному облучению

The increased risk of colorectal cancer following ionizing radiation exposure was demonstrated in a number of epidemiological studies. Earlier, no impact of occupational radiation exposure on colorectal cancer incidence or mortality was observed in a cohort of workers of the nuclear industrial facility, Mayak Production Association (PA). Extension of the follow-up of the cohort and improvement of dose estimates for personnel made it possible to update the earlier findings. The study objective is to assess the risk of colorectal cancer incidence associated with chronic occupational radiation exposure taking into account non-radiation factor effects. The study cohort included 22,377 workers employed at the reactor, plutonium-producing and radiochemical plants of Mayak PA (hiring period 1948–1982; follow-up period ended on December 31, 2018). Using the Poisson regression (EPICURE software), the relative risks (RRs with 95 % confidence intervals, (95 % CI)) of colorectal cancer incidence were estimated depending on the most significant non-radiation factors (sex, age, smoking, alcohol consumption, excessive body mass and obesity, intestinal polyps, chronic colitis). These values were also calculated for certain ranges of occupational exposure doses relying on data provided by ‘The Mayak Worker Dosimetry System – 2013’. The linear model was used to analyze the dose-response relationship. In the study cohort, the RR of colorectal cancer incidence was lower in females than in males: 0.72 (95 % CI: 0.55; 0.96) for colon and 0.48 (95 % CI: 0.34; 0.67) for rectum. The increased RR of the rectum cancer incidence was observed for cases with intestinal polyps: 3.42 (95 % CI: 1.68; 6.19). The colon cancer incidence risk increased with increasing age of workers, but other non-radiation factors were not shown to affect the results. This study supported the earlier results: no association was observed between the risk of colorectal cancer incidence and doses of occupational external gamma-ray or internal alpha-particle exposures.

Does Elderly-Onset Inflammatory Bowel Disease Increase Risk of Colorectal Cancer? A Systematic Review and Meta-Analysis.

Although younger adults with inflammatory bowel disease (IBD) are known to have an increased risk of developing colorectal cancer (CRC), the impact of IBD on CRC risk in elderly patients is not yet fully understood. Therefore, we conducted this systematic review and meta-analysis to address this knowledge gap. We thoroughly searched Embase, PubMed, and Scopus, covering the literature from inception to 31 August 2023, in any language. We enrolled population-based cohort studies that appraised the risk of CRC development in elderly patients (≥60 years) with IBD as compared to the non-IBD population. Our meta-analysis provided pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effect model. Out of 3904 citations, 3 eligible cohort studies were ultimately included, reporting 694 CRC events in 35,187 patients with IBD. According to analysis, the risk of developing CRC did not increase in patients with elderly-onset IBD (RR = 1.17 [95% CI: 0.86-1.47]; I2 = 62.6%). This lack of a significant association was observed in both patients with Crohn's disease (RR = 1.28 [95% CI: 0.88-1.69]) and ulcerative colitis (RR = 0.99 [95% CI: 0.90-1.09]) (p for interaction = 0.166). Our findings revealed no significant increase in the risk of incident CRC in patients with elderly-onset IBD, suggesting that intense screening of these patients for CRC may not be necessary.

Dietary medium-chain fatty acids and risk of incident colorectal cancer in a predominantly low-income population: a report from the Southern Community Cohort Study

BackgroundNo prospective observational study has specifically examined the associations between dietary intakes of medium-chain fatty acids and risk of colorectal cancer. ObjectivesThis study examined the association between dietary intakes of medium-chain fatty acids and colorectal cancer risk overall and by racial subgroups in a predominantly low-income United States population. MethodsThis prospective study included 71,599 eligible participants aged 40 to 79 who were enrolled in the Southern Community Cohort Study between 2002 and 2009 in 12 southeastern United States states. Incident colorectal cancer cases were ascertained via linkage to state cancer registries, which was completed through 31 December, 2016. The dietary intakes of medium-chain fatty acids were assessed using a validated 89-item food frequency questionnaire. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between intakes of medium-chain fatty acids and risk for incident colorectal cancer. ResultsAmong 71,599 participants, 48,008 (67.3%) were Black individuals and 42,260 (59.0%) were female. A total of 868 incident colorectal cancer cases occurred during a median follow-up of 13.7 y. Comparing the highest to the lowest quartile, high intake of dodecanoic acid/lauric acid (C12:0) was associated with reduced risk of colorectal cancer among White participants (HR: 0.52; 95% CI: 0.30, 0.91; P-trend = 0.05), but not in Black individuals (HR: 0.92; 95% CI, 0.68, 1.24; P-trend = 0.80) in multivariable-adjusted models. No associations were found between intakes of hexanoic acid/caproic acid (C6:0), octanoic acid/caprylic acid (C8:0), or decanoic acid/capric acid (C10:0) and risk of incident colorectal cancer overall or within racial subgroups. ConclusionsIn a predominantly low-income United States population, an increased dietary C12:0 intake was associated with a substantially reduced risk of colorectal cancer only among White individuals, but not in Black individuals.

Plant-based dietary patterns, genetic predisposition and risk of colorectal cancer: a prospective study from the UK Biobank

BackgroundPlant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk.MethodsThis prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model.ResultsOver a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81–0.96) and 0.91 (95% CI, 0.84–0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males.ConclusionsOur results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.

Serum 25-Hydroxyvitamin D Levels and Risk of Colorectal Cancer: An Age-Stratified Analysis

The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults. Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders. During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals. Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease.

Association of modifiable lifestyle with colorectal cancer incidence and mortality according to metabolic status: prospective cohort study.

Metabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population. This prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized based on the presence or absence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into "favorable," "intermediate", and "unfavorable") with CRC incidence and mortality, stratified by metabolic health status. During a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). MetS was associated with greater CRC incidence (HR = 1.24, 95% CI: 1.16 - 1.33) and mortality (HR = 1.24, 95% CI: 1.08 - 1.41) when compared with those without MetS. An unfavorable lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 - 1.36) and mortality (HR = 1.36, 95% CI: 1.16 - 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable lifestyle with MetS had a higher risk (HR = 1.56, 95% CI: 1.38 - 1.76) and mortality (HR = 1.75, 95% CI: 1.40 - 2.20) than those adopting a favorable healthy lifestyle without MetS. This study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with MetS.

Saturated fatty acid intake, genetic risk and colorectal cancer incidence: A large-scale prospective cohort study.

Previous investigations mainly focused on the associations of dietary fatty acids with colorectal cancer (CRC) risk, which ignored gene-environment interaction and mechanisms interpretation. We conducted a case-control study (751 cases and 3058 controls) and a prospective cohort study (125 021 participants) to explore the associations between dietary fatty acids, genetic risks, and CRC. Results showed that high intake of saturated fatty acid (SFA) was associated with a higher risk of CRC than low SFA intake (HR =1.22, 95% CI:1.02-1.46). Participants at high genetic risk had a greater risk of CRC with the HR of 2.48 (2.11-2.91) than those at low genetic risk. A multiplicative interaction of genetic risk and SFA intake with incident CRC risk was found (PInteraction = 7.59 × 10-20 ), demonstrating that participants with high genetic risk and high SFA intake had a 3.75-fold greater risk of CRC than those with low genetic risk and low SFA intake. Furthermore, incorporating PRS and SFA into traditional clinical risk factors improved the discriminatory accuracy for CRC risk stratification (AUC from 0.706 to 0.731). Multi-omics data showed that exposure to SFA-rich high-fat dietary (HFD) can responsively induce epigenome reprogramming of some oncogenes and pathological activation of fatty acid metabolism pathway, which may contribute to CRC development through changes in gut microbiomes, metabolites, and tumor-infiltrating immune cells. These findings suggest that individuals with high genetic risk of CRC may benefit from reducing SFA intake. The incorporation of SFA intake and PRS into traditional clinical risk factors will help improve high-risk sub-populations in individualized CRC prevention.

Abstract 6451: Dietary medium-chain fatty acids and risk of incident colorectal cancer in a predominantly low-income population: a report from the Southern Community Cohort Study (SCCS)

Abstract Purpose: Previous studies have investigated medium-chain fatty acids (MCFAs) as a part of saturated fat intake and risk of colorectal cancer (CRC). However, unlike long-chain saturated fatty acids, MCFAs possess many unique properties, including inhibition of pro-carcinogenic bacteria, biofilm formation, and induction of apoptosis. Further, C12:0 has been consistently shown in vitro to exhibit the most potent anti-microbial properties in a dose-dependent manner compared to other MCFAs. Black Americans have the highest CRC incidence and mortality across all racial subgroups in the US. In a predominantly low-income population, we aimed to examine whether dietary intake of MCFAs is associated with a reduced risk of CRC overall and among racial subgroups. Methods: The daily intake of total energy and individual nutrients, including MCFAs, was derived from a food frequency questionnaire. Multivariable-adjusted Cox regression was used to assess the associations between dietary intake of MCFAs and the risk of incident CRC during the 13.75-year follow up after adjustment for confounders. Results: Among 71,599 eligible participants, 868 incident CRC cases were identified (622 Blacks, 220 Whites and 26 other racial groups). High intake of C12:0 was significantly associated with a reduced risk of CRC only in White participants in a dose-response manner (for highest VS lowest quartile: HR, 0.37; 95% CI, 0.17 to 0.80; P for trend =0.0068). This protective association primarily appeared in White participants at high risk of CRC, such as those aged 50 years or older, overweight or obese, ever smokers, or living in a neighborhood with greater deprivation. On the other hand, we did not find a significant association in Black participants (HR, 0.87; 95% CI, 0.59 to 1.27); P for trend =0.72). However, there was a marginal linear association in Black participants with the lowest deprivation index while the association disappeared among Black participants with higher deprivation index. Finally, we found from the NHANES 2005-2016, a representative sample of the US general population, that Black Americans had the lowest intake of MCFAs across all racial subgroups and, overall, intakes of MCFAs decreased with reducing poverty-income ratio. No associations were found between intakes of C6:0, C8:0, or C10:0 and the risk of incident CRC overall or within the racial group. Conclusion: In this predominantly low-income population, increasing dietary C12:0 intake was associated with a substantially reduced risk of CRC only among White participants, but not in Black participants. This racial difference in associations may be because Black Americans consumed the lowest levels of MCFAs in all racial groups while a much higher proportion of Black participants had lactose intolerance and a lower proportion of them consumed lactose-free fermented foods. Citation Format: Lei Fan, Xiangzhu Zhu, Qingxia Chen, Xiang Huang, Mark D. Steinwandel, Martha Shrubsole, Qi Dai. Dietary medium-chain fatty acids and risk of incident colorectal cancer in a predominantly low-income population: a report from the Southern Community Cohort Study (SCCS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6451.

Leukocyte telomere length and mitochondrial DNA copy number association with colorectal cancer risk in an aging population

In this study, we evaluated the association of blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) with the risk of incident colorectal cancer (CRC). We studied and followed-up a cohort of Russian men and women (aged 45 – 69 years, n = 9360, 54% female) from the HAPIEE study for 15 years. Using the nested case-control design, we selected cases with incident CRC among those free from any baseline cancer (n = 146) and sex- and age-stratified controls among those free from baseline cancer and cardiovascular disease and alive at the end of the follow-up (n = 799). We employed multivariable-adjusted logistic regression to estimate the odds ratios (ORs) of CRC per 1 decile of LTL or mtDNA-CN. We observed an inverse association of LTL and mtDNA-CN baseline values with the 15-year risk of incident CRC. Carriers of shorter telomeres had an increased 15-year risk of incident CRC with adjusted OR 3.2 (95% CI: 2.56 – 3.87, P &lt; 0.001) per 1 decile decrease in LTL, independent of baseline age, sex, smoking, body mass index, blood pressure, lipid levels, and education. Similarly, lower mtDNA-CN was associated with the higher risk of incident CRC with adjusted OR 1.7 (95% CI: 1.12 – 1.89, P &lt; 0.001) per 1 decile decrease in mtDNA-CN, independent of the aforementioned factors. Using the modified values of LTL and mtDNA-CN adjusted for multiple factors and their interactions with a case–control status, the ORs of CRC were 2.53 and 1.52 per 1 decile decrease in adjusted baseline LTL and mtDNA-CN, respectively. In conclusion, LTL and mtDNA-CN were independent inverse predictors of the 15-year risk of CRC in the Russian cohort. These findings highlight the relevance for subsequent research to exploit the mechanisms through which LTL and mtDNA-CN may reflect human health.

The relationship between serum uric acid and colorectal cancer: a prospective cohort study

Serum uric acid (SUA) may play an important role in the occurrence of colorectal cancer (CRC). This study aims to explore the association of SUA with the risk of CRC incidence by drawing data from the Kailuan Study. We prospectively examined the association between SUA and risk of CRC incidence among 93,356 Chinese. Eligible participants were divided into three groups based on their tertiles of SUA. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. During a median follow-up of 13.02 years, 583 new-onset CRC cases were identified. After adjustments were made for confounders, participants in the highest tertiles of SUA exhibited a 1.55-fold increased risk of CRC compared with patients with the lowest SUA levels (HRT3 vs. T1 = 1.55, 95% CI: 1.09–2.30). The associations of SUA with the risk of CRC were slightly reduced but remained substantial in the competing risk analyses when treating CRC unrelated death as the competing risk event. This study found a positive association of SUA with CRC incidence. Specific prevention efforts could be focused on the population with higher levels of SUA.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning Ten Years after a Negative Colonoscopy, among Screen-Eligible Adults 76 to 85 Years Old.

Few empirical data are available to inform older adults' decisions about whether to screen or continue screening for colorectal cancer based on their prior history of screening, particularly among individuals with a prior negative exam. Using a retrospective cohort of older adults receiving healthcare at three Kaiser Permanente integrated healthcare systems in Northern California (KPNC), Southern California (KPSC), and Washington (KPWA), we estimated the cumulative risk of colorectal cancer incidence and mortality among older adults who had a negative colonoscopy 10 years earlier, accounting for death from other causes. Screen-eligible adults ages 76 to 85 years who had a negative colonoscopy 10 years earlier were found to be at a low risk of colorectal cancer diagnosis, with a cumulative incidence of 0.39% [95% CI, 0.31%-0.48%) at 2 years that increased to 1.29% (95% CI, 1.02%-1.61%) at 8 years. Cumulative mortality from colorectal cancer was 0.04% (95% CI, 0.02%-0.08%) at 2 years and 0.46% (95% CI, 0.30%-0.70%) at 8 years. These low estimates of cumulative colorectal cancer incidence and mortality occurred in the context of much higher risk of death from other causes. Knowledge of these results could bear on older adults' decision to undergo or not undergo further colorectal cancer screening, including choice of modality, should they decide to continue screening. See related commentary by Lieberman, p. 6.