Risk Of Incident Colorectal Cancer Research Articles

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.

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.

Title: Involvement of unsaturated fatty acid biosynthesis in CRC progression based on in vitro and in silico studies

Obesity is one of the risk factors concerns of colorectal cancer (CRC), the most common type of gastrointestinal cancer, due to the changing lifestyle and especially diet. There are various molecular pathways associated with obesity and the risk of CRC incidence, such as insulin resistance or elevated plasma free fatty acids, which alter the signaling pathways of intestinal epithelial cells. The aim of this study was to better understand the significance of unsaturated fatty acid biosynthesis on pathogenesis of colon cancer in obese. Based on GSE20931 dataset, obese individuals affected by CRC had higher increased gene expression than non-obese individuals. The analysis showed that in obese individuals, the 16 signaling pathway genes were activated and increased (FDR <0.05) significantly. The biosynthetic pathway of unsaturated fatty acids showed a cross-talk with the arachidonic acid metabolism pathway and the PPAR signaling pathway is influenced and regulated via these pathways. The biosynthetic pathway of unsaturated fatty acids consisting of 22 genes, were analyzed using GEO data and revealed that 4 genes (HSD17B12, TECR, FADS2, ELOVL5) from this pathway were significantly increased (FDR <0.05). These data were validated based on TCGA data (Adj.p.value <0.001). The expression level of candidate genes in HT-29 cells decreased significantly (P.value <0.01), and PPARγ expression increased under linoleic acid treatment (200 μM) compared to control cells. Moreover, in presence of linoleic acid treatment, migration, colony formation, and proliferation decreased (P.value <0.01) in presence of treatment. In summary, the Biosynthesis pathway of unsaturated fatty acids is an interesting and critical pathway in CRC.

Incidence and Survival Outcomes of Colorectal Cancer in Long-Term Metformin Users with Diabetes: A Population-Based Cohort Study Using a Common Data Model

Background and aims: Previous studies have reported that metformin use in patients with diabetes mellitus may reduce the risk of colorectal cancer (CRC) incidence and prognosis; however, the evidence is not definite. This population-based cohort study aimed to investigate whether metformin reduces the risk of CRC incidence and prognosis in patients with diabetes mellitus using a common data model of the Korean National Health Insurance Service database from 2002 to 2013. Methods: Patients who used metformin for at least 6 months were defined as metformin users. The primary outcome was CRC incidence, and the secondary outcomes were the all-cause and CRC-specific mortality. Cox proportional hazard model was performed and large-scaled propensity score matching was used to control for potential confounding factors. Results: During the follow-up period of 81,738 person-years, the incidence rates (per 1000 person-years) of CRC were 5.18 and 8.12 in metformin users and non-users, respectively (p = 0.001). In the propensity score matched cohort, the risk of CRC incidence in metformin users was significantly lower than in non-users (hazard ratio (HR), 0.58; 95% CI (confidence interval), 0.47–0.71). In the sensitivity analysis, the lag period extending to 1 year showed similar results (HR: 0.63, 95% CI: 0.51–0.79). The all-cause mortality was significantly lower in metformin users than in non-users (HR: 0.71, 95% CI: 0.64–0.78); CRC-related mortality was also lower among metformin users. However, there was no significant difference (HR: 0.55, 95% CI: 0.26–1.08). Conclusions: Metformin use was associated with a reduced risk of CRC incidence and improved overall survival.

Association between proteinuria and incident colorectal cancer: analysis of a nationwide population-based database

ObjectivesThis study aimed to assess whether adults with proteinuria were at a higher risk of incident colorectal cancer (CRC) than those without proteinuria using a large-scale population-based database.DesignA retrospective observational...

Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals.

There is strong evidence to support prophylactic aspirin use for the prevention of colorectal cancer. However recent recommendations suggest the risk of bleeding in older individuals outweighs the benefit. We sought to determine whether some older individuals might still benefit from aspirin based on their genetic susceptibility.

Irritable Bowel Syndrome and Long-Term Risk of Cancer: A Prospective Cohort Study Among 0.5 Million Adults in UK Biobank.

To investigate the prospective association of irritable bowel syndrome (IBS) with long-term risk of overall, site-specific cancer and cancer-specific mortality in general population. Participants free of inflammatory bowel disease, celiac disease, and any cancer at baseline from the UK Biobank were included, with patients with IBS as the exposure group and non-IBS patients as the reference group. The primary outcome was the incidence of overall cancer and cancer-specific mortality. Secondary outcomes included site-specific cancers and types of digestive cancers. The Cox proportional hazard model was used to investigate the associated risk of incident malignancies and related mortality. Among 449,595 participants, 22,338 (5.0%) were diagnosed with IBS. During a median of 12.2-year follow-up, 2,937 cases of incident cancer were identified in patients with IBS (11.47 per 1,000 person-years), compared with 60,556 cases in reference individuals (12.51 per 1,000 person-years). Of these cases, 512 and 12,282 cancer-specific deaths occurred in IBS and non-IBS groups. Compared with non-IBS, the adjusted hazard ratio for overall cancer and cancer-specific mortality was 0.97 (95% confidence interval: 0.93-1.00, P = 0.062) and 0.83 (0.76-0.91, P < 0.001) among patients with IBS. Specifically, decreased risk of digestive (0.79 [0.71-0.89]), particularly colon (0.75 [0.62-0.90]) and rectal (0.68 [0.49-0.93]), cancers was observed in patients with IBS. Further sensitivity analysis and subgroup analysis by age and sex indicated similar results. Compared with the general population, IBS does not increase the overall risk of cancer. Conversely, IBS is associated with lower risk of incident colorectal cancer and cancer-specific mortality.