Urinary metabolites of 1,3-butadiene, benzene and toluene and colorectal cancer incidence: a clinical case-control study.

Background: Although type 2 diabetes (T2D) has been linked to an increased risk of colorectal cancer (CRC), a causal relationship remains to be established. Also, the influence of hyperglycemia and impaired beta-cell function on CRC remains to be determined. Methods: We performed a Mendelian randomization (MR) study using common single nucleotide polymorphisms (SNPs) identified from prior genome-wide association studies for T2D (78 SNPs), fasting glucose (36 SNPs), glycosylated hemoglobin (HbA1c, 11 SNPs), and homeostatic model assessment for beta-cell function (HOMA-B, 13 SNPs) (all SNPs reached genome-wide significance at 5 x10-8). We first assessed the association of each SNP with CRC risk using logistic regression in 26,357 CRC cases and 20,505 control participants in the Colon Cancer Family Registry, Colorectal Transdisciplinary Study and the Genetics and Epidemiology of Colorectal Cancer Consortium. The MR estimates for the association of each risk factor with CRC were calculated using the inverse-variance weighted method that combines summary data on the association of the SNPs with each trait derived from previous genome-wide association studies. Given the potential sex difference in the relationship of metabolic factors with CRC, all analyses were performed in men and women separately. Results: We did not find any statistically significant association between each of the genetically predicted risk factors and CRC incidence for sex-stratified or combined analyses. The odds ratios (ORs) of CRC associated with genetic risk of T2D were 1.02 (95% confidence interval [CI], 0.95-1.08, P=0.62) in women and 0.96 (95% CI, 0.90-1.03, P=0.25) in men. For fasting glucose, the ORs of CRC associated with one mmol/L increment was 0.91 (95% CI, 0.68-1.20, P=0.49) in women and 1.20 (95% CI, 0.90-1.59, P=0.22) in men, respectively. For HbA1c, the ORs of CRC associated with one percent increment was 0.83 (95% CI, 0.57-1.22, P=0.35) in women and 0.99 (95% CI, 0.67-1.45, P=0.95) in men. For HOMA-B, the ORs of CRC associated with a unit increase in log-transformed measurement was 0.92 (95% CI, 0.53-1.60, P=0.76) in women and 0.77 (95% CI, 0.44-1.35, P=0.36) in men. Conclusion: Our findings do not support a causal association of T2D, impaired beta-cell function, and hyperglycemia with CRC risk. However, the null findings may be due to weak instrument bias since these common SNPs account for only a limited proportion of the inter-individual variation in these glycemic traits. Citation Format: Mingyang Song, Yiwen Lu, Marc Gunter, Neil Murphy, Barbara L. Banbury, Wenjie Ma, Jennifer Prescott, Graham Casey, Stephen B. Gruber, Edward L. Giovannucci, Ulrike Peters, Andrew T. Chan. Type 2 diabetes and glycemic traits in relation to colorectal cancer risk: A Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 235.

Novel, Emerging Risk Factors for Colorectal Cancer Remain Understudied

Lower Endoscopy and Prevention of Colon Cancer

3532 Background: Colorectal cancer (CRC) incidence is increasing in young patients ( < 50 years old) without a clear etiology. Emerging data has implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC (YO-CRC) is poorly defined. Colibactin producing E. Coli and fadA producing Fusobacterium nucleatum can drive CRC carcinogenesis, however their effects across the age spectrum are unknown. Methods: We performed a meta-analysis of fecal metagenomics sequencing from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate species and known microbial derived factors (colibactin and FadA) associated with CRC as a function of age. Generalized linear mixed effects regression was used to model the predicted prevalence of gene families and taxa as a non-linear function of age. Two-stage individual patient data meta-analysis (IPDMA) with adjustment for gender, CRC status, and body mass index was also used to estimate summary odds ratios for colibactin, F. nucleatum, and E. Coli. Interaction ORs were obtained to assess the difference in the effect of each gene or taxa on CRC case status in YO-CRC. Shannon Diversity index and metabolic pathway differences in the fecal metagenome for YO-CRC patients were assessed using phyloseq and MetaCyc respectively using an IPDMA approach. Results: Summary odds ratios (OR) for CRC were increased relative to controls with the presence of colibactin (OR 1.92 95%CI 1.08-3.38), fadA (OR 4.57 95%CI 1.63-12.85), and F. nucleatum (OR 6.93 95%CI 3.01-15.96) in models of all patients adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of F. nucleatum (OR = 1.40 [1.18; 1.65] and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. No difference was observed for Shannon Diversity (OR 1.36 95%CI 0.68-2.72) or MetaCyc pathways in YO-CRC patients. Species relative abundance was differentially enriched in YO-CRC relative to old CRC patients and controls for five species- Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis. Conclusions: Strong associations with CRC status were observed for colibactin, fadA, and F. nucleatum with increased F. nucleatum in older patients. Several species were enriched in YO-CRC patients including B. wadsworthia which can produce carcinogenic sulfur metabolites and is increased with adherence to a sulfur microbial diet-low in vegetables and legumes. A sulfur microbial diet has also been associated with higher incidence of YO-CRC in population studies (Nguyen Gastroenterology 2021). Additional study is warranted to understand causal mechanisms of enriched species observed in YO-CRC patients.

Past research on the social determinants of colorectal cancer (CRC) has shown that lower socioeconomic status (SES) is associated with a higher risk of CRC. Similar to SES at the individual level, the neighbourhood social environment may partly affect the development of CRC. Although one important aspect of the neighbourhood social environment is social capital, no large-scale follow-up study has examined its potential effect on CRC. We examined whether neighbourhood "linking social capital," which is established through social relationships and may enable individuals to gain health-promotional resources, is associated with the incidence of and mortality related to CRC, after adjusting for individual- and familial-level factors. This longitudinal study, conducted in Sweden, comprised over 2 million men and over 2 million women aged 25years or older. The follow-up period started on January 1, 2002 and continued until first incidence of CRC, death due to CRC, death from any other cause, emigration, or the end of the study period on December 31, 2015. We identified over 20,000 CRC cases during the follow-up period. We used multilevel logistic regression models to calculate odds ratios (ORs) with 95% confidence intervals. After adjustment for potential confounding factors, higher ORs of CRC were observed in individuals who lived in neighbourhoods with low, relative to high social capital. Our results suggest that neighbourhood linking social capital has independent effects on CRC. Future studies could explore how simple interventions that can build linking social capital can enhance people's health.

Background Outcomes of endoscopic surveillance following surgery for colorectal cancer (CRC) vary with the incidence and timing of CRC detection, at anastomosis or elsewhere in the colorectum. We performed systematic review and meta-analysis to evaluate the incidence of CRCs identified during surveillance colonoscopies of patients with previous CRC surgery. Methods We searched PubMed, EMBASE, SCOPUS, and the Cochrane Central Register through January 1, 2018, to identify studies investigating rates of CRCs at anastomoses or other colorectal locations after curative surgery for primary CRC. We collected data from randomized controlled, prospective, and retrospective cohort studies. Data were analyzed by multivariate meta-analytic models. Results From 2,373 citations, we selected 27 studies with 15,803 index CRCs (89% stage I-III CRCs). Overall, 296 CRCs at non-anastomotic locations were reported over time periods of more than 16 years (cumulative incidence, 2.2% of CRCs; 95% CI, 1.8%-2.9%). The risk of non-anastomotic CRC is shown in figure A (figure 1A) and significantly decreased after 36 months or more from resection, compared with that before this time point (odds ratio for non-anastomotic CRCs at 36–48 months vs 6–12 months after surgery, 0.61; 95% CI, 0.37–0.98; P=.031); 53.7% of all non-anastomotic CRCs were detected within 36 months from surgery. One hundred fifty-eight anastomotic CRCs were detected over more than 16-years follow-up (cumulative incidence of 2.7%; 95% CI, 1.9%-3.9%). The risk of anastomotic CRCs is shown in figure B (figure 1B), and was significantly lower after 24 months or more from resection than before (odds ratio for CRCs at anastomoses at 25–36 months after surgery vs. 6–12 months, 0.56; 95% CI, 0.32–0.98; P=.036); 90.8% of anastomotic CRCs were detected within 36 months from surgery. Conclusions After surgery for CRC, the highest risk of anastomotic and non-anastomotic CRCs is highest during 36 months after surgery - risk decreases thereafter. Patients who have undergone CRC resection should be evaluated by colonoscopy more closely during this time period. Longer intervals may be considered thereafter.

Does Colon Polyp Surveillance Improve Patient Outcomes?

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 < 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 < 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.

BackgroundThe potential association between dietary inflammatory index (DII) and colorectal cancer (CRC) risk, as well as colorectal adenomas (CRA) risk, has been extensively studied, but the findings remain inconclusive. We conducted this systematic review and dose-response meta-analysis to investigate the relationship between the DII and CRC and CRA.MethodsWe comprehensively searched the PubMed, Embase, Cochrane Library, and Web of Science databases for cohort and case-control studies reporting the relationship between DII and CRA, or between DII and CRC, as of 15 July 2025. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Dose-response analysis was conducted where possible. Subgroup analyses were conducted to account for possible sources of heterogeneity. Funnel plot, Egger’s test, and Begg’s test were utilized to assess publication bias.ResultsTwenty-two studies were included, involving 7,612 CRA patients, 25,359 CRC patients, and 896,592 controls. The pooled ORs for CRC and CRA in total population comparing the highest DII to the lowest DII were 1.61 (95% CI, 1.42–1.83) and 1.19 (95% CI, 0.96–1.47), respectively. The pooled ORs for CRC and CRA per unit increase in DII were 1.14 (95% CI, 1.08–1.20) and 1.19 (95% CI, 1.03–1.38), respectively. Stratification by sex revealed a positive association between DII and CRC risk in both males and females. However, this association was stronger in males (Highest DII vs. lowest DII: OR = 1.67, 95% CI [1.39, 2.00]) (Continues DII: OR = 1.16, 95%CI [1.06, 1.26]). Dose-response analysis revealed a nonlinear positive correlation between CRC risk and DII (P for non−linearity < 0.0001).ConclusionsOur findings suggest that dietary habits characterized by a high inflammatory index may increase the risk of CRA and CRC.Trial registration PROSPERO registration number: CRD42025641934.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12937-025-01202-9.

Interim 10-year results from the Nordic-European Initiative on Colorectal Cancer (NordICC), a randomized controlled trial (RCT) of screening colonoscopy, demonstrated a statistically significant reduction in colorectal cancer (CRC) incidence but not mortality, contrary to results from 4 flexible sigmoidoscopy RCTs. We constructed CRC incidence and mortality Kaplan-Meier curves through 10 years to standardize comparisons across RCTs and examined CRC screen detection and stage. Novel analyses of 1 flexible sigmoidoscopy RCT (Prostate, Lung, Colorectal, and Ovarian cancer screening trial [PLCO]) assessed year-by-year mortality in screen-detected CRCs. At 10 years, all RCTs demonstrated statistically significant CRC incidence reductions with screening (ratio = 0.77, 95% confidence interval [CI] = 0.70 to 0.84, to ratio = 0.82, 95% CI = 0.69 to 0.97, vs control arm; P ≤ .011). Two flexible sigmoidoscopy RCTs and NordICC showed no statistically significant CRC mortality reduction (ratio = 0.84, 95% CI = 0.64 to 1.10, to ratio = 0.90, 95% CI = 0.69 to 1.18; P = .10-0.23). In 3 flexible sigmoidoscopy RCTs and NordICC, relative reductions were greater in CRC incidence than CRC mortality, but only NordICC reported higher CRC mortality with screening vs the control arm for the first 7 years. In contrast, PLCO observed fewer CRC deaths with screening by year 2 (ratio = 0.59; P = .03), and screen-detected CRCs were less often advanced (odds ratio = 0.26; P < .001) or fatal (ratio = 0.50; P < .001). After 10 years, NordICC is similar to 2 flexible sigmoidoscopy RCTs in observing statistically significant reductions in CRC incidence but not CRC mortality. However, only NordICC observed greater CRC mortality with screening vs the control arm for 7 years. Granular analyses of CRC cases and deaths in NordICC, paralleling our PLCO analyses, could provide insight into why CRC mortality results differ in NordICC vs flexible sigmoidoscopy RCTs.

To determine whether school milk consumption in childhood decreased the risk of adult colorectal cancer, the authors conducted a national population-based, case-control study of 562 cases and 571 controls. The authors identified new cases of colorectal cancer in 2007 among people aged 30-69 years from the New Zealand Cancer Registry. Controls were randomly selected from the electoral rolls and frequency matched to cases in 5-year age groups. Participation in school milk programs was associated with a reduced odds ratio for colorectal cancer (odds ratio (OR) = 0.70, 95% confidence interval (CI): 0.51, 0.96). Odds ratios decreased with increasing numbers of bottles of milk drunk compared with no school milk (for 1-799 bottles, OR = 1.04, 95% CI: 0.66, 1.67; for 800-1,199 bottles, OR = 0.81, 95% CI: 0.51, 1.29; for 1,200-1,599 bottles, OR = 0.62, 95% CI: 0.41, 0.93; for 1,600-1,799 bottles, OR = 0.57, 95% CI: 0.37, 0.90; and for 1,800 or more bottles, OR = 0.62, 95% CI: 0.41, 0.96). Participation in school milk programs in New Zealand was associated with a 2.1% reduction (95% CI: 0.7, 3.5) in the odds ratio for colorectal cancer for every 100 half-pint bottles drunk (1 half-pint bottle = 284 mL).

Colorectal cancer (CRC) ranked 3rd for cancer incidence and 4th for cancer death worldwide. Despite the increasing number of CRC studies, the etiology is not yet clear. In this study, we investigated the effects of the dinner-to-bed time, post-dinner walk and sleep duration on the risk for CRC.We conducted a matched case-control study based on hospital population. We involved 166 patients had a newly histologically confirmed CRC without previous treatment and 166 healthy healthy residents matched by age and gender at Fujian Medical Union Hospital. A self-designed questionnaire was used to information on demographic characteristics, dinner-to-bed time, post-dinner walk, sleep duration, and other behavioral factors. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CIs) to assess the effect of dinner-to-bed time, post-dinner walking, and sleep duration as well as their joint effect on the risk of CRC at different genders.The adjusted odds ratio (AOR) of CRC for subjects with shorter dinner-to-bed time (2.0–2.9 h) were 2.527 (95% CIs = 1.127–5.337), relative to those with longer dinner-to-bed time (≥4 h), the difference was statistically significant (P < .05). Post-dinner walk was associated with a significantly decreased CRC risk (AOR = 0.339, 95% CIs = 0.203–0.865) compared with post-dinner non-walk. Compared with 6–9 h of sleep duration, the risk OR of CRC were 3.843 (95% CIs = 2.767–7.800, P < .05) and 2.12 (95% CIs = 0.754–5.959, P > .05) for long (≥9 h) and short (<6 h) sleep duration. The risk of CRC individuals with shorter dinner-to-bed time and post-dinner non-walk caused higher risk than those with longer dinner-to-bed time and post-dinner walk (AOR = 3.361, 95% CIs = 2.043–6.316). The risk of CRC was 2.231 (95% CIs = 1.089–3.762, P < .001), with a shorter dinner-to-bed time and ≥9 hours of sleep duration.We found that shorter dinner-to-bed time (<3 h), post-dinner walk, and long sleep duration (≥9 h) were seems to be related to CRC and may increase the risk of CRC.

Obesity is a rising public health problem in the U.S. and worldwide and excess body mass index (BMI, kg/m2) is a recognized risk factor for colorectal cancer (CRC). However, the role of weight change over the adult life course and timing of the excess BMI in relation to the incidence and mortality of CRC is not well understood. With &amp;gt;15 years of follow-up, we prospectively evaluated the risk of CRC incidence (n=3, 092) and mortality (n=931) in association with adult weight change among men and women (n=131, 814) recruited in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial at ages 55 to 74 between 1993 and 2001. At baseline, participants filled out a questionnaire reporting their weight and height at ages 20 years, 50 years, and baseline, allowing us to assess weight change from early to middle, middle to late, and early to late adulthood. Hazard ratios (HRs) and 95% confidence intervals (CI) were computed using multivariable-adjusted proportional hazard regression models. Higher BMI at all ages was associated with an increased risk of CRC incidence (p-trend=0.05, 0.0003 &amp; 0.0001 for ages 20, 50 and baseline, respectively). Compared with individuals whose BMI never exceeded 25 kg/m2 over their lifetime, those who first exceeded a BMI of 25 kg/m2 in early adulthood had a slightly higher risk of CRC (HR=1.3, CI:1.1-1.4) than those whose BMI did not exceed 25 kg/m2 until middle age (HR=1.2, CI:1.1-1.3) or later (HR=1.2, CI: 1.0-1.3). Moreover, compared with stable weight, weight gain &amp;gt;4 kg per 5 years from early adulthood to middle or late adulthood was associated with an increased risk of CRC (HR=1.2, CI: 1.1-1.4 for both periods). The increased risks for weight gain &amp;gt;4 kg/5 years between early to middle adulthood appeared more pronounced for those with normal BMI at age 20 (HR=1.3, CI: 1.1-1.5). For CRC mortality, higher BMI at age 50 and baseline, but not age 20, was associated with increased risk (p-trend = 0.0002, 0.0002, and 0.3, respectively). Compared to those whose BMI never exceeded 25 kg/m2, those who first exceeded a BMI of 25 kg/m2 in early adulthood had an increased risk of mortality (HR=1.2, CI: 1.0-1.5), but no association was found for those whose BMI did not exceed 25 kg/m2 until middle adulthood or later. A higher risk of CRC mortality was observed for weight gain &amp;gt;4 kg/5 years from early adulthood to middle or late adulthood (HR=1.5, CI: 1.1-1.9 and HR=1.7, CI:1.4-2.1, respectively), especially among those with normal BMI at age 20 (HR=1.5, CI: 1.1-2.0 and HR=1.7, CI:1.3-2.2, respectively). Exceeding normal weight in early adulthood and weight gain from early to middle or late adulthood were associated with increased risks of both CRC incidence and mortality. These findings highlight the harms of excess BMI in early adulthood, the importance of maintaining healthy weight throughout the adulthood, and the potential benefit of weight control programs for CRC prevention. Citation Format: Wen-Yi Huang, Steven C. Moore, Kathryn Hughes Barry, Sonja I. Berndt. A prospective study of excess weight and weight change in adulthood and risk of colorectal cancer incidence and mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3735.

Screening, Surveillance, and Primary Prevention for Colorectal Cancer: A Review of the Recent Literature

In this large MR analysis of a Japanese population, a positive association was found between genetically predicted high total cholesterol (TC) levels and an increased risk of colorectal cancer. Therefore, lowering TC levels by lifestyle modifications or medications may be justified for the purpose of preventing colorectal cancer.