Colon Subsite Research Articles

The Persistence of Hypertriglyceridemia and the Risk of Early Onset Colorectal Cancer According to Tumor Subsites: A Nationwide Population-Based Study.

The incidence of early-onset colorectal cancer (EoCRC) is increasing worldwide. The association between hypertriglyceridemia (HTG) and EoCRC risk remains unclear. We conducted a nationwide cohort study of 3,340,635 individuals aged 20-49 years who underwent health checkups between 2009 and 2011 under the Korean National Health Insurance Service. HTG was defined as serum triglyceride (TG) level ≥ 150 mg/dL. According to the change in TG status, participants were categorized into persistent normotriglyceridemia (NTG; group 1), NTG to HTG (group 2), HTG to NTG (group 3), and persistent HTG (group 4) groups. The EoCRC incidence was followed up until 2019. In total, 7,492 EoCRC cases developed after a mean of 6.05 years of follow-up. Group 4 had the highest risk of EoCRC (adjusted hazard ratio [aHR], 1.097; 95% confidence interval [CI], 1.025 to 1.174). While the risk of rectal cancer was significantly increased in groups 3 and 4 (aHR [95% CI], 1.236 [1.076 to 1.419] and 1.175 [1.042-1.325], respectively), no significant risk differences were observed in right colon cancer. In group 4, male sex and diabetes were associated with a further increased risk of EoCRC (aHR [95% CI], 1.149 [1.082 to 1.221] and 1.409 [1.169 to 1.699], respectively). In addition, there was a dose-response relationship between serum TG levels and the risk of EoCRC (p for trends < 0.0001). Persistent HTG increased the risk of EoCRC, which was significantly higher only for rectal cancer and marginally higher for other colonic subsites.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with pulmonary metastasis: a cohort study.

Studies of unresectable colorectal cancer pulmonary metastasis (CRPM) have rarely analyzed patient prognosis from the perspective of colonic subsites. This study aimed to evaluate the effects of primary tumor resection (PTR) on the prognosis of patients with unresectable pulmonary metastases of transverse colon cancer pulmonary metastasis (UTCPM), hepatic flexure cancer pulmonary metastasis (UHFPM), and splenic flexure cancer pulmonary metastasis (USFPM). Patients were identified from the Surveillance, Epidemiology, and End Results database between 2000 and 2018. The Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). The Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. This study included 1294 patients: 419 with UHFPM, 636 with UTCPM, and 239 with USFPM. Survival analysis for OS and CSS in the PTR groups, showed that there were no statistical differences in the the UHFPM, UTCPM, and USFPM patients. There were statistical differences in the UHFPM, UTCPM, and USFPM patients for OS and CSS. Three non-PTR subgroups showed significant statistical differences for OS and CSS. We confirmed the different survival rates of patients with UTCPM, UHFPM, and USFPM and proved for the first time that PTR could provide survival benefits for patients with unresectable CRPM from the perspective of the colonic subsites of the transverse colon, hepatic flexure, and splenic flexure.

Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases.

The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.

Abstract A007: Trends and racial and ethnic disparities in colorectal cancer by anatomic subsite and stage at diagnosis, 2000-2019

Abstract Introduction: Subsite-specific incidence rates (IRs) of colorectal cancer (CRC) vary considerably by race/ethnicity and patterns of stage at diagnosis by anatomic subsite may reflect access to CRC screening. We examine racial and ethnic trends and differences in CRC IRs by stage and subsite in a screening eligible population. Methods: The Surveillance, Epidemiology, and End Results 17 registries database identified 374,582 patients aged 50-74 diagnosed with adenocarcinoma CRC from 2000-2019. Stage-specific (In situ/localized, regional, distant), age-adjusted IRs were computed by subsite (proximal, distal, rectal) and race/ethnicity (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic). Trends in IRs were measured using annual percentage change (APC) and absolute change. Proportional stage distribution (percent contribution of each cancer stage) were calculated and compared using chi-squared tests. Supplemental analyses compared differences in stage distribution within API subgroups (Filipino, Chinese, Japanese, Korean, Vietnamese, Pacific Islander). Results: From 2000-2019, IRs decreased across all CRC subsites and racial and ethnic groups except for AIAN patients. For AIAN patients, the incidence of rectal cancer increased over time (APC=1.24, p&amp;lt;0.05), while IRs for proximal and distal colon cancer remained stable over time. When stratified by stage, the steepest percent decreases in IRs were among in situ/localized and regional stages, with smaller declines for distant stage tumors across all race/ethnic groups. As of 2018-2019, IRs of distant stage tumors of the proximal (IRR=2.09, p&amp;lt;0.001) and distal colon (IRR=1.51, p&amp;lt;0.001) cancers remained 1.5 to 2 times higher among Black patients compared to White patients, while API and Hispanic patients had similar or lower distant stage IRs for proximal and distal subsites. In contrast, stage-specific rectal cancer IRs were similar across race/ethnic groups. Proportional stage analysis revealed an increase in distant stage tumors and a decrease in in situ/localized stage tumors over time among distal colon and rectal subsites across all race/ethnic groups. As of 2018-2019, Black patients had higher percentages of distant stage tumors and lower percentages of in situ/localized tumors compared to other race/ethnic groups, and this was consistent across all three subsites. In supplemental analysis, Pacific Islander patients had higher percentages of distant stage CRC (22.6%), while Japanese patients had higher percentages of in situ/localized CRC (16.85%). Conclusions: Our findings suggest that racial and ethnic disparities in CRC vary by subsite, with Black patients experiencing higher rates of distant stage tumors of the proximal and distal colon. While decreases in CRC IRs highlight the positive impact of CRC screening and early detection efforts, more work is needed to reduce persistent disparities for Black patients. Variation by stage within API subgroups emphasizes the need to examine disparities among disaggregated racial and ethnic groups. Citation Format: Kristin M. Primm, Andrea Malabay, Taylor Curry, Shine Chang. Trends and racial and ethnic disparities in colorectal cancer by anatomic subsite and stage at diagnosis, 2000-2019 [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A007.

Explaining regional variations in colon cancer survival in Ontario, Canada: a population-based retrospective cohort study

ObjectivesRegional variation in cancer survival is an important health system performance measurement. We evaluated if regional variation in colon cancer survival may be driven by differences in the patient population,...

Associations of cigarette smoking, alcohol drinking and body mass index with survival after colorectal cancer diagnosis by anatomic subsite: a prospective patient cohort study in Japan.

Cigarette smoking, alcohol drinking and obesity are known to be risk factors for colorectal cancer. These factors may affect survival after diagnosis, but evidence has been inconsistent. We investigated subsite-specific associations between prediagnosis smoking, alcohol drinking and body mass index and survival in colorectal cancer. Subjects were 1300 patients (colon 778; rectum 502; concurrent 20) with histologically confirmed colorectal cancer diagnosed during 1997-2013 at a single institution in Japan. Histories of smoking and alcohol drinking, height and prediagnosis weight were assessed using a self-administered questionnaire. Using Cox proportional hazards model, hazard ratios and 95% confidence intervals of mortality were estimated. During a median follow-up period of 6.7years, 479 deaths were documented. Ever-smoking was associated with an increased risk of all-cause death among patients with colon cancer (hazard ratio: 1.47; 95% confidence interval: 1.07-2.02 compared with never-smoking). According to colon subsite, this increased risk was clear in patients with proximal colon cancer (hazard ratio: 2.09; 95% confidence interval: 1.28-3.40). There was no association between smoking and rectal cancer survival. Alcohol drinking was not associated with survival for either colon or rectal cancer. Among patients with rectal cancer, higher body mass index was associated with a lower risk of all-cause (Ptrend=0.0006) and disease-specific death (Ptrend=0.02). For colon cancer, lower body mass index tended to be associated with a higher risk of all-cause death (Ptrend=0.05). The results indicate that lifestyles identified as risk factors for colorectal cancer may impact differently on patient survival according to anatomic subsite.

Food processing groups and colorectal cancer risk in Morocco: evidence from a nationally representative case-control study.

The aim of this study was to investigate the association between the consumption of foods and drinks from different food processing categories using the NOVA classification and CRC risk among Moroccan adults. 1453 cases and 1453 matched controls aged at least 18years and recruited from the 5 greater Moroccan regions were interviewed by trained investigators about their habitual diet using a standardized food frequency questionnaire (FFQ). Foods were categorized according to their degree of processing by the NOVA classification. Intakes of each food processing group were categorized into tertiles based on the distribution of controls with the lowest tertile considered as the reference category. Multivariable conditional logistic regression models were used to assess the association between each group and CRC risk (Odds Ratio (OR) and 95% Confidence Intervals (CI)), taking relevant confounders into account. High consumption of unprocessed or minimally processed foods (NOVA group 1) was significantly inversely (OR = 0.82, 95%CI = 0.72-0.93), while high consumption of ultra-processed foods and drink products (NOVA group 4) was significantly positively (OR = 1.40, 95% CI = 1.22-1.61) associated with CRC risk as compared to the lowest intake group. These results were similar for colon and rectum sub-sites. This is the first study to evaluate the association between the NOVA classification groups and CRC risk in an African country. Our results suggest that the consumption of ultra-processed foods and drink products may be associated with an increased risk of developing CRC, but longitudinal studies are needed to confirm these results.

Impact of primary tumor resection on the survival of patients with unresectable colon cancer liver metastasis at different colonic subsites: a propensity score matching analysis

Objective To investigate the effect of primary tumor resection (PTR) on the prognosis of patients with unresectable colon cancer liver metastasis (UCCLM) at seven colonic subsites using the Surveillance, Epidemiology, and End Results (SEER) database. Methods Propensity score matching (PSM) was performed to balance selection bias using all available variables that could be of potential relevance. After matching, the groups were redefined in a 1:1 ratio using the nearest method. Cancer-specific survival (CSS) was compared among the patients of PTR and non-PTR groups. Cox regression models were used to identify the prognostic factors for CSS. Results CSS was significantly different between all groups. Cox regression analysis showed that PTR was an independent prognostic factor for all groups. After PSM, PTR significantly prolonged CSS for all groups. Subgroup analysis showed that PTR did not improve the prognosis of N2 stage patients in the cecum, ascending colon, and descending colon groups; T1 + T2 stage patients in the hepatic flexure group; and patients with a tumor size ≤5 cm in the splenic flexure group. Segmental colectomy could prolong CSS of patients in the cecum, ascending colon, transverse colon, splenic flexure, and sigmoid colon groups, while extended colectomy could prolong CSS of patients in the hepatic flexure and descending colon groups. Conclusion At different colonic subsites, UCCLM patients had different CSS. PTR could improve their prognosis, however, N stage, T stage, and tumor size are important reference indicators. In addition to patients in the hepatic flexure and descending colon groups, we suggested that patients in other groups should choose segmental colectomy.

Transcriptome-Wide Association Study for Inflammatory Bowel Disease Reveals Novel Candidate Susceptibility Genes in Specific Colon Subsites and Tissue Categories

Genome-wide association studies [GWAS] for inflammatory bowel disease [IBD] have identified 240 risk variants. However, the benefit of understanding the genetic architecture of IBD remains to be exploited. Transcriptome-wide association studies [TWAS] associate gene expression with genetic susceptibility to disease, providing functional insight into risk loci. In this study, we integrate relevant datasets for IBD and perform a TWAS to nominate novel genes implicated in IBD genetic susceptibility. We applied elastic net regression to generate gene expression prediction models for the University of Barcelona and University of Virginia RNA sequencing project [BarcUVa-Seq] and correlated expression and disease association research [CEDAR] datasets. Together with Genotype-Tissue Expression project [GTEx] data, and GWAS results from about 60 000 individuals, we employed Summary-PrediXcan and Summary-MultiXcan for single and joint analyses of TWAS results, respectively. BarcUVa-Seq TWAS revealed 39 novel genes whose expression in the colon is associated with IBD genetic susceptibility. They included expression markers for specific colon cell types. TWAS meta-analysis including all tissues/cell types provided 186 novel candidate susceptibility genes. Additionally, we identified 78 novel susceptibility genes whose expression is associated with IBD exclusively in immune (N = 19), epithelial (N = 25), mesenchymal (N = 22) and neural (N = 12) tissue categories. Associated genes were involved in relevant molecular pathways, including pathways related to known IBD therapeutics, such as tumour necrosis factor signalling. These findings provide insight into tissue-specific molecular processes underlying IBD genetic susceptibility. Associated genes could be candidate targets for new therapeutics and should be prioritized in functional studies.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with liver metastasis: a preliminary population-based analysis

PurposeStudies on unresectable colorectal cancer liver metastasis(CRLM) rarely analyze the prognosis of the patients from the point of colonic subsites. We aimed to evaluate the effect of primary tumor resection (PTR) and different scope of colectomy on the prognosis of patients with unresectable transverse colon cancer liver metastasis (UTCLM), hepatic flexure cancer liver metastasis (UHFLM), and splenic flexure cancer liver metastasis (USFLM).Patients and methodsThe patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival.ResultsIn total, this study included a cohort of 1960 patients: 556 cases of UHFLM, 1008 cases of UTCLM, and 396 cases of USFLM. The median survival time of whole patients was 11.0 months, ranging from 7.0 months for UHFLM patients to 15.0 months for USFLM patients. USFLM patients had the best OS and CSS, followed by UTCLM patients. UHFLM patients had the worst OS and CSS (All P < 0.001). PTR could improve the OS and CSS of UTCLM, UHFLM, and USFLM (All P < 0.001). Subgroups analysis revealed that USFLM patients with tumor size≤5 cm and negative CEA had not demonstrated an improved OS and CSS after PTR. Multivariate analysis showed that PTR and perioperative chemotherapy were common independent prognostic factors for UHFLM, UTCLM, and USFLM patients. There was no difference between segmental colon resection and larger colon resection on CSS of UHFLM, UTCLM, and USFLM patients.ConclusionsWe confirmed the different survival of patients with UTCLM, UHFLM, and USFLM, and for the first time, we proved that PTR could provide survival benefits for patients with unresectable CRLM from the perspective of colonic subsites of transverse colon, hepatic flexure, and splenic flexure. Besides, PTR may not improve the prognosis of USFLM patients with CEA- negative or tumor size≤5 cm. For oncologic outcomes, we concluded that segmental colon resection seemed an effective surgical procedure for UTCLM, UHFLM, and USFLM.

Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci.

Background & AimsThe association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource.MethodsWe collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing. We performed genome-wide SNP genotyping from blood leukocytes. Statistical approaches and bioinformatics software were used for QTL identification and downstream analyses.ResultsWe provided a complete quantification of gene expression and alternative splicing across colon subsites and described their differences. We identified thousands of expression and splicing QTLs and defined their enrichment at genome-wide regulatory regions. We found that part of the SNP-based heritability of diseases affecting colon tissue, such as colorectal cancer and inflammatory bowel disease, but also of diseases affecting other tissues, such as psychiatric conditions, can be explained by the identified QTLs. We provided candidate effector genes for multiple phenotypes. Finally, we provided the Colon Transcriptome Explorer web application.ConclusionsWe provide a large characterization of gene expression and splicing across colon subsites. Our findings provide greater etiologic insight into complex traits and diseases influenced by transcriptomic changes in colon tissue.

Extended healthy lifestyle index and colorectal cancer risk in the Moroccan population.

Little is known about the combined effect of different lifestyle factors on CRC incidence among populations living in developing countries. In this study, we sought to create an Extended Healthy Lifestyle Index (EHLI) and to investigate its association with CRC risk in the Moroccan population. A large case-control study including 1516 cases and 1516 controls, matched on age, sex and center were recruited in 5 Moroccan university hospital centers between 2009 and 2017. EHLI scores, including 9 modifiable factors (smoking, alcohol consumption, physical activity intensity, BMI, fruit and vegetables consumption, drinks that promote weight gain, red and processed meat, relatively unprocessed cereals and/or pulses, and dairy products consumption) were assigned to lifestyle information derived from the participants. We assessed the score based on the answers on each of the nine lifestyle components as unhealthy/un-compliant (0 point), healthy/compliant (1 point) and 0.5 for partial compliance to the recommendation. Conditional logistic regression models were used to assess the association between the EHLI and CRC risk and to estimate multivariate ORs and their 95% confidence intervals (CIs). All potential confounder variables were considered. After adjusting for potential confounding factors, a significant decrease in the risk of overall CRC was observed when comparing the highest EHLI category with the lowest index category (0.39, 95% CI: 0.33-0.47). These results did not differ by colon or rectum subsite. Combined healthy lifestyle factors are associated with a significantly lower incidence of CRC in Moroccan populations. Prevention strategies should consider targeting of multiple lifestyle factors.

Meat subtypes and colorectal cancer risk: A pooled analysis of 6 cohort studies in Japan.

Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population‐based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01‐1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05‐1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10‐1.87) for “3 times/wk or more” vs “less than 1 time/wk”. Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97‐2.00; P trend = .04) for “almost every day” vs “less than 1 time/wk”. No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese.

Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients

Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS, NRAS, and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.

Lymph node yield and tumour subsite are associated with survival in stage I\u2013III colon cancer: results from a national cohort study

BackgroundIt has been suggested that apart from tumour and nodal status, a range of patient-related and histopathological factors including lymph node yield and tumour location seems to have prognostic implications in stage I–III colon cancer. We analysed the prognostic implication of lymph node yield and tumour subsite in stage I–III colon cancer.MethodsData on patients with stage I to III adenocarcinoma of the colon and treated by curative resection in the period from 2003 to 2011 were extracted from the Danish Colorectal Cancer Group database, merged with information from the Danish National Patient Register and analysed.ResultsA total of 13,766 patients were included in the analysis. The 5-year overall survival ranged from 59.3% (95% CI 55.7–62.9%) (lymph node yield 0–5) to 74.0% (95% CI 71.8–76.2%) (lymph node yield ≥ 18) for patients with stage I–II disease (p < 0.0001) and from 36.4% (95% CI 29.8–43.0%) (lymph node yield 0–5) to 59.4% (95% CI 56.6–62.2%) (lymph node yield ≥ 18) for patients with stage III disease (p < 0.0001). The 5-year overall survival for tumour side left/right was 59.3% (95% CI 57.9–60.7%)/64.8% (CI 63.4–66.2%) (p < 0.0001). In the seven colonic tumour subsites, the 5-year overall survival ranged from 56.6% (95% CI 51.8–61.4%) at splenic flexure to 65.8% (95% CI 64.5–67.2%) in the sigmoid colon (p < 0.0001). In a cox regression analysis, lymph node yield and tumour side right/left were found to be prognostic factors. Tumours at the hepatic and splenic flexures had an adverse prognostic outcome.ConclusionFor stage I–III colon cancer, a lymph node yield beyond the recommended 12 lymph nodes was associated with improved survival. Both subsite in the right colon, as well as subsite in the left colon, turned out with adverse prognostic outcome questioning a simple classification into right-sided and left-sided colon cancer.

Allium vegetables are associated with reduced risk of colorectal cancer: A hospital-based matched case-control study in China.

The present study aimed to investigate and identify the association between the intake of allium vegetables and colorectal cancer (CRC) in population. A hospital-based matched case-control study was conducted between June 2009 and November 2011 in three hospitals. Eight hundred thirty three consecutively recruited cases of CRC were frequency matched to 833 controls by age (within 2.5 years of difference), sex, and residence area (rural/urban). Demographic and dietary information were collected via face-to-face interviews using a validated food frequency questionnaire. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by using unconditional logistic regression. A decreased CRC risk was observed for the consumption of total (aORs of high total allium intake compared with low total allium intake=0.21, 95% CI=0.14-0.30, P trend <0.001) and several individual allium vegetables including garlic, garlic stalks, leek, onion, and spring onion (P trend <0.05). By further sex-stratified analysis, allium vegetable intake was demonstrated to be inversely associated with the risk of CRC in both men and women. However, the association of garlic intake with cancer risk was not significant among those with distal colon cancer (aOR=0.53, 95% CI=0.27-1.05, P trend=0.248). In this analysis in a Northeast Chinese population, both men and women that the consumption of allium vegetables is associated with a reduced risk of CRC, regardless of colonic tumor subsite, with the exception of garlic intake in distal colon cancer.

Benzene exposure at workplace and risk of colorectal cancer in four Nordic countries

ObjectiveThe aim of this case-control study was to assess the effect of occupational benzene exposure on the risk of colorectal cancer, including its subtypes. MethodsThe study included 181,709 colon cancer and 109,227 rectal cancer cases diagnosed between 1961 and 2005 in Finland, Iceland, Norway and Sweden. Cases were identified from the Nordic Occupational Cancer Study (NOCCA) cohort. Five controls per case were selected from the same cohort, matched for country, birth year, and sex. Occupational benzene exposure for each study participant was estimated by linking their job titles to country specific job-exposure matrices. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by using conditional logistic regression models. The results were adjusted for physical strain at work, formaldehyde, ionizing radiation and wood dust. ResultsIncreased risk was observed for all colorectal cancer (OR = 1.12, 95% CI 1.05–1.18) for the high decile of cumulative benzene exposure, indicating a statistically significant dose-response relationship. This excess risk was mainly seen in ascending colon (OR = 1.27, 95% CI 1.13–1.43), and transversal colon (OR = 1.21, 95% CI 1.01–1.41). The ORs in the highest exposure category were markedly higher in women than in men in all subsites of colon and rectum. ConclusionThis study showed an association between workplace benzene exposure and colorectal cancer. The risk was restricted to ascending and transversal colon, and was the strongest among women.

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

Background:Observational studies have shown that physical activity levels are inversely, and sedentary behaviours are positively, associated with colorectal cancer risk; however, whether these relationships are consistent across anatomical subsites is uncertain.Methods:We investigated the associations between colorectal cancer and physical activity (metabolic equivalents (METs)-hours per week), and indicators of sedentary behaviour (television watching time and time spent using computers) among 430 584 men and women enroled in the UK Biobank. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models.Results:After a median follow-up time of 5.6 years, 2391 incident colorectal cancer cases were recorded. High (⩾60-MET-hours per week) vs low (<10-MET-hours per week) total physical activity was associated with a lower colon cancer risk (HR=0.84, 95% CI: 0.72–0.98; p-trend=0.04), with comparable relationships observed for proximal and distal colon tumours, but no association for rectal cancer. Higher levels of television watching time were associated with greater colon cancer risk (HR for ⩾5 h per day vs ⩽1 h per day=1.32, 95% CI: 1.04–1.68; p-trend=0.007). Time spent using computers was not associated with colorectal cancer risk.Conclusions:Higher levels of physical activity were associated with lower colon cancer risk, with no heterogeneity by colonic subsite. Sedentary behaviour (television watching) was associated with elevated colon cancer risk.

Increased colon cancer risk after severe Salmonella infection.

BackgroundColon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.Methods and findingsWe performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade.ConclusionsPatients diagnosed with severe salmonellosis have an increased risk of developing cancer in the ascending/transverse parts of the colon. This risk concerns particularly S. Enteritidis infection, suggesting a contribution of this major foodborne pathogen to colon cancer development.

Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study.

The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.