• Colorectal cancer
• Community pharmacy
• Directed point-of-care
• FIT kits
• Screening program

• Humans
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/epidemiology
• Middle Aged
• Male
• Female
• Pharmacists/organization & administration
• Early Detection of Cancer/methods
• Prospective Studies
• Community Pharmacy Services/organization & administration
• Aged
• Adult
• Risk Factors
• Occult Blood
• Point-of-Care Systems
• Professional Role
• Point-of-Care Testing
• Mass Screening/methods
• Prevalence

• Colon cancer
• Colorectal cancer
• Metabolic factors
• Rectal cancer
• Umbrella review

• Humans
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/metabolism
• Risk Factors
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/etiology
• Metabolic Syndrome/metabolism
• Obesity/complications
• Obesity/epidemiology
• Obesity/metabolism
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/etiology

• Colorectal neoplasms
• Sulfonylurea
• Type 2 diabetes

• Humans
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/epidemiology
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/complications
• Case-Control Studies
• Sulfonylurea Compounds/therapeutic use
• Male
• Female
• Middle Aged
• Aged
• Hypoglycemic Agents/therapeutic use
• Risk Factors
• Odds Ratio
• Adult

• Humans
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/prevention & control
• Colorectal Neoplasms/etiology
• Male
• Female
• Case-Control Studies
• Middle Aged
• Aged
• Risk Factors
• Risk Reduction Behavior
• Italy/epidemiology
• Diet/statistics & numerical data
• Diet/adverse effects
• Diabetes Mellitus/epidemiology
• Diabetes Mellitus/prevention & control

• 21378 Fondazione AIRC per la ricerca sul cancro ETS (AIRC)
• P20229A9S5 Ministero dell'Università e della Ricerca (MUR)

• Case–control study
• Colorectal cancer
• Dietary zinc intake
• SLC30A8 rs3802177 variant

• Female
• Humans
• Case-Control Studies
• Logistic Models
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/genetics
• Zinc
• Republic of Korea/epidemiology
• Risk Factors
• Zinc Transporter 8

• NCCRI•NCCI 52210-52211, 2022 International Cooperation & Education Program of the National Cancer Center, Korea
• 2310470 National Cancer Center, Korea
• 2021R1A2C2008439 National Research Foundation of Korea

• benign neoplasms
• colorectal tumors
• national health programs
• periodontitis

Background: Non-cancer causes of death in patients with colorectal cancer (CRC) have not received much attention until now. The purpose of the current study is to investigate the non-cancer causes of death in patients with CRC at different periods of latency.

Methods: Eligible patients with CRC were included from the Surveillance, Epidemiology, and End Results (SEER) database, and standardized mortality ratios (SMRs) were calculated using the SEER*Stat software 8.3.8.

Results: A total of 475,771 patients with CRC were included, of whom 230,841 patients died during the follow-up period. Within 5 years, CRC was the leading cause of death. Over time, non-cancer causes of death account for an increasing proportion. When followed up for more than 10 years, non-cancer deaths accounted for 71.9% of all deaths worldwide. Cardiovascular diseases were the most common causes of non-cancer deaths, accounting for 15.4% of the total mortality. Patients had a significantly higher risk of death from septicemia within the first year after diagnosis compared with the general population (SMR, 3.39; 95% CI, 3.11–3.69). Within 5–10 years after CRC diagnosis, patients had a significantly higher risk of death from diabetes mellitus (SMR, 1.27; 95% CI, 1.19–1.36). During the course of more than 10 years, patients with CRC had a significantly higher risk of death from atherosclerosis (SMR 1.47; 95% CI, 1.11–1.9).

Conclusions: Although CRC has always been the leading cause of death in patients with CRC, non-cancer causes of death should not be ignored. For patients with cancer, we should not only focus on anti-tumor therapies but also pay attention to the occurrence of other risks to prevent and manage them in advance.

• and End Results database
• cardiovascular disease
• colorectal cancer
• epidemiology
• non-cancer deaths
• standardized mortality ratios
• surveillance

• Body mass index
• Colorectal cancer
• Diabetes
• Waist circumference

Converging evidences showed that people with diabetes mellitus (DM) have significantly higher risk for different cancers, of which the exact mechanism underlying the association has not been fully realized. Short-chain fatty acids (SCFAs), the fermentation products of the intestinal microbiota, are an essential source for energy supply in gut epithelial cells. They have been reported to improve intestinal barrier integrity, prevent microbial translocation, and further dampen inflammation. Gut dysbiosis and reduction in SCFA-producing bacteria as well as SCFAs production in the intestine are commonly seen in metabolic disorders including DM and obesity. Moreover, inflammation can contribute to tumor initiation and progression through multiple pathways, such as enhancing DNA damage, accumulating mutations in tumor suppressor genes Tp53, and activating nuclear factor-kappa B (NF-κB) signaling pathways. Based on these facts, we hypothesize that lower levels of microbial SCFAs resulted from gut dysbiosis in diabetic individuals, enhance microbial translocation, and increase the inflammatory responses, inducing tumorigenesis ulteriorly. To this end, we will discuss protective properties of microbial SCFAs and explore the pivotal roles SCFAs played in the link of DM with cancer, so as to take early precautions to reduce the risk of cancer in patients with DM.

• cancer
• diabetes
• gut dysbiosis
• inflammation
• short-chain fatty acids

• AGR2
• AMPK
• ROS
• autophagy
• colorectal cancer
• diabetes mellitus

To conduct an anatomic site-specific case–control study of candidate colorectal cancer (CRC) risk factors.

Case–control study of US veterans with >1 colonoscopy during 1999–2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs.

21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95).

Candidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.

• cancer epidemiology
• colorectal cancer
• epidemiology

• Cancer
• Cohort study
• Diabetes mellitus
• Poisson regression

• HHSN268201100012C NHLBI NIH HHS
• HHSN268201100009I NHLBI NIH HHS
• HHSN268201100010C NHLBI NIH HHS
• HHSN268201100008C NHLBI NIH HHS
• HHSN268201100007C NHLBI NIH HHS
• HHSN268201100011I NHLBI NIH HHS
• HHSN268201100011C NHLBI NIH HHS
• HHSN268201100006C NHLBI NIH HHS
• HHSN268201100005I NHLBI NIH HHS
• HHSN268201100007I NHLBI NIH HHS
• HHSN268201100005G NHLBI NIH HHS
• HHSN268201100008I NHLBI NIH HHS
• HHSN268201100009C NHLBI NIH HHS
• HHSN268201100005C NHLBI NIH HHS

The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. While several clinical studies show a higher incidence of CC and a lower survival rate in diabetics, others report no association. Our own experience indicates that diabetes does not seem to worsen the prognosis once the tumor is present. Despite this controversy, there are no wide‐spectrum molecular studies that delve into the impact of T2DM‐related mechanisms in colon carcinogenesis. Here, we present a transcriptomic and proteomic profiling of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of which have T2DM. We used gene set enrichment and network approaches to extract relevant pathways in diabetics, referenced them to current knowledge, and tested them using in vitro techniques. Through our transcriptomics approach, we identified an unexpected overlap of pathways overrepresented in diabetics compared to nondiabetics, in both tumor and normal mucosa, including diabetes‐related metabolic and signaling processes. Proteomic approaches highlighted several cancer‐related signaling routes in diabetics found only in normal mucosa, not in tumors. An integration of the transcriptome and proteome analyses suggested the deregulation of key pathways related to colon carcinogenesis which converged on tumor initiation axis TEAD/YAP‐TAZ as a potential initiator of the process. In vitro studies confirmed upregulation of this pathway in nontumor colon cells under high‐glucose conditions. In conclusion, T2DM associates with deregulation of cancer‐related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support that in diabetic patients, the local microenvironment in normal colon mucosa may be a factor driving field cancerization promoting carcinogenesis. Our results set a new framework to study links between diabetes and colon cancer, including a new role of the TEAD/YAP‐TAZ complex as a potential driver.

• carcinogenesis
• colon cancer
• diabetes
• field cancerization
• omics
• systems biology

• acromegaly
• cancer
• colon
• colonoscopy
• screening

• Colon cancer
• elderly population
• Saudi Arabia

• Aged
• Aged, 80 and over
• Colonoscopy/methods
• Colorectal Neoplasms/diagnosis
• Cross-Sectional Studies
• Early Detection of Cancer/methods
• Female
• Humans
• Logistic Models
• Male
• Mass Screening/methods
• Occult Blood
• Primary Health Care/methods
• Saudi Arabia

Previous studies have shown a positive association between type 2 diabetes (T2D) and colorectal cancer (CRC) risk. However, it is uncertain whether this association differs by duration of T2D or sex. We thus investigated the associations of T2D and its duration with the risk of incident CRC.

We followed 87,523 women from the Nurses’ Health Study (1980–2012) and 47,240 men from the Health Professionals Follow-up Study (1986–2012). Data on physician-diagnosed T2D was collected at baseline with a questionnaire and updated biennially. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

We documented 3000 CRC cases during up to 32 years of follow-up. Among men, T2D was associated with increased risk of CRC compared to those without T2D (HR: 1.42; 95% CI: 1.12–1.81). This positive association persisted in sensitivity analyses by excluding CRC identified within 1 year of diabetes diagnosis and patients with T2D who used hypoglycaemic medications. Among women, T2D was positively, but not statistically significantly, associated with CRC risk (HR: 1.17; 95% CI: 0.98–1.39).

Our findings support that T2D was associated with a moderately higher risk of developing CRC in men; a weaker, nonsignificant positive association was observed in women.

• Hispanic Americans
• SEER Program
• colorectal neoplasm
• epidemiology
• neoplasm staging
• risk factors

• incidence of FOBT-positivity
• incidence of colorectal cancer
• person-year method
• retrospective cohort study
• risk factors for colorectal cancer

Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ² test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (p< 0.001 for rs1111875, p=0.001 for rs7923837). For rs1111875, increased risk of CRC was observed in TC or TC/CC than CC individuals (p<0.001, OR= 1.780, 95%CI= 1.385-2.287; p<0.001, OR= 1.695, 95%CI= 1.335-2.152). For rs7923837, increased CRC risk was observed in AG, GG, and AG/GG than AA individuals (p< 0.001, OR= 1.520, 95%CI= 1.200-1.924; p=0.036, OR= 1.739, 95%CI= 0.989-3.058; p< 0.001, OR= 1.540, 95%CI= 1.225-1.936). This finding highlights the potentially functional alteration with HHEX rs1111875 and rs7923837 polymorphisms may increase CRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

• HHEX
• colorectal cancer
• genetic variants
• type 2 diabetes mellitus

• cancer
• diabetes
• gender
• insulin
• metformin

• cancer
• diabetes
• hospitalization
• risk factors
• surgery unit

• Biomarker
• Carcinoma
• Colon
• Energy balance
• Molecular pathologic epidemiology
• PRKA

• Animals
• Carcinoma/complications
• Carcinoma/etiology
• Carcinoma/metabolism
• Carcinoma/prevention & control
• Colorectal Neoplasms/complications
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/prevention & control
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/etiology
• Diabetes Mellitus, Type 2/metabolism
• Diabetes Mellitus, Type 2/prevention & control
• Diet/adverse effects
• Diet, Healthy
• Energy Intake
• Energy Metabolism
• Evidence-Based Medicine
• Health Transition
• Healthy Lifestyle
• Humans
• Models, Biological

• K07 CA190673 NCI NIH HHS
• R01 CA151993 NCI NIH HHS
• R35 CA197735 NCI NIH HHS

The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.

• Diabetes
• Intestine
• Colon
• Biomechanics
• Motor-sensory
• Gut microbiota
• Symptoms

• Acromegaly/complications
• Acromegaly/diagnosis
• Acromegaly/epidemiology
• Adult
• Case-Control Studies
• Cohort Studies
• Colonic Polyps/complications
• Colonic Polyps/diagnosis
• Colonic Polyps/epidemiology
• Colonoscopy/statistics & numerical data
• Female
• Humans
• Male
• Middle Aged
• Prevalence

Previous large-scale cohort studies conducted in Korea have found a positive association between diabetes mellitus (DM) and colorectal cancer (CRC) in men only, in contrast to studies of other populations that have found significant associations in both men and women.

A total of 1070 CRC cases and 2775 controls were recruited from the National Cancer Center, Korea between August 2010 and June 2013. Self-reported DM history and the duration of DM were compared between cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary and polytomous logistic regression models.

DM was associated with an elevated risk of CRC in both men (OR, 1.47; 95% CI, 1.13 to 1.90) and women (OR, 1.92; 95% CI, 1.24 to 2.98). This association remained when we controlled for age, body mass index, alcohol consumption, and physical activity level. In sub-site analyses, DM was associated with distal colon cancer risk in both men (multivariate OR, 2.04; 95% CI, 1.39 to 3.00) and women (multivariate ORs, 1.99; 95% CI, 1.05 to 3.79), while DM was only associated with rectal cancer risk in women (multivariate OR, 2.05; 95% CI, 1.10 to 3.82). No significant association was found between DM and proximal colon cancer risk in either men (multivariate OR, 1.45; 95% CI, 0.88 to 2.41) or women (multivariate OR, 1.79; 95% CI, 0.78 to 4.08).

Overall, DM was associated with an increased risk of CRC in Koreans. However, potential over-estimation of the ORs should be considered due to potential biases from the case-control design.

• Diabetes mellitus, Colorectal neoplasms, Colonic neoplasms

• Cancer
• Diabetes
• Insulin
• Metformin
• Obesity

• Aged
• Aged, 80 and over
• Biomarkers
• Case-Control Studies
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/epidemiology
• Diabetes Mellitus, Type 2/therapy
• Female
• Glycated Hemoglobin
• Humans
• Male
• Middle Aged
• Neoplasms/epidemiology
• Neoplasms/etiology
• Retrospective Studies
• Risk Factors
• Time Factors

Type 2 diabetes mellitus has been associated with an excess risk of colorectal cancer, although the time–risk relationship is unclear, and there is limited information on the role of antidiabetic medications.

We examined the association between type 2 diabetes, antidiabetic medications, and the risk of colorectal cancer, considering also duration of exposures.

We analyzed data derived from two companion case–control studies conducted in Italy and Spain between 2007 and 2013 on 1,147 histologically confirmed colorectal cancer cases and 1,594 corresponding controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional multiple logistic regression models, adjusted for socioeconomic factors and major potential confounding factors.

Overall, 14% of cases and 12% of controls reported a diagnosis of diabetes, corresponding to an OR of colorectal cancer of 1.21 (95% CI 0.95–1.55). The OR was 1.49 (95% CI 0.97–2.29) for a duration of diabetes of at least 15 years. The OR was 1.53 (95% CI 1.06–2.19) for proximal colon cancer, 0.94 (95% CI 0.66–1.36) for distal colon cancer, and 1.32 (95% CI 0.94–1.87) for rectal cancer. In comparison with no use, metformin use was associated with a decreased colorectal cancer risk (OR 0.47, 95% CI 0.24–0.92), while insulin use was associated with an increased risk (OR 2.20, 95% CI 1.12–4.33); these associations were stronger for longer use (OR 0.36 and 8.18 for ≥10 years of use of metformin and insulin, respectively).

This study shows evidence of a positive association between diabetes and colorectal cancer, mainly proximal colon cancer. Moreover, it indicates a negative association between colorectal cancer and metformin use and a positive association for insulin use.

• antidiabetic medications
• colorectal cancer
• diabetes
• insulin
• metformin
• risk factor

• Birth weight
• Childhood
• Cohort
• Colon cancer
• Colorectal cancer
• Proportional hazards model
• Prospective studies
• Rectal cancer

• Adult
• Aged
• Birth Weight/genetics
• Child
• Cohort Studies
• Colorectal Neoplasms/etiology
• Female
• Humans
• Male
• Middle Aged
• Risk Factors

• 281419 European Research Council
• P2C HD050924 NICHD NIH HHS

• Diabetes
• Metformin
• Radiotherapy
• Rectal cancer
• Tumor response

• Aged
• Case-Control Studies
• Chemoradiotherapy
• Diabetes Complications
• Female
• Humans
• Hypoglycemic Agents/pharmacology
• Male
• Metformin/pharmacology
• Middle Aged
• Rectal Neoplasms/complications
• Rectal Neoplasms/pathology
• Rectal Neoplasms/radiotherapy
• Recurrence

• Adult
• Aged
• Asian/statistics & numerical data
• Attitude to Health/ethnology
• Colonoscopy
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/ethnology
• Colorectal Neoplasms/psychology
• Comorbidity
• Early Detection of Cancer/psychology
• Evaluation Studies as Topic
• Female
• Follow-Up Studies
• Health Knowledge, Attitudes, Practice
• Health Services Accessibility
• Humans
• Male
• Middle Aged
• Patient Acceptance of Health Care/ethnology
• Patient Acceptance of Health Care/psychology
• Practice Patterns, Physicians'
• Vietnam

• R01 CA124397 NCI NIH HHS
• R01 CA 124397 NCI NIH HHS

• colorectal cancer
• diabetes
• outcome

Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se.

To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines.

The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”.

The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included.

Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment).

Publication bias seemed to be present. Only published data were used in the analyses.

The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.

• Alaska Native
• American Indian
• Native Hawaiian
• indigenous
• participatory research
• research ethics

• Age of Onset
• Diabetes Mellitus/drug therapy
• Diabetes Mellitus/epidemiology
• Dose-Response Relationship, Drug
• Humans
• Hypoglycemic Agents/therapeutic use
• Neoplasms/epidemiology
• Neoplasms/etiology
• Occupational Exposure/statistics & numerical data
• Risk Factors

• OTG-88588 Canadian Institutes of Health Research
• WT086113 Wellcome Trust

• Adult
• Aged
• Aged, 80 and over
• Body Mass Index
• Colonic Neoplasms/epidemiology
• Colonic Neoplasms/etiology
• Comorbidity
• Diabetes Complications/epidemiology
• Diabetes Complications/etiology
• Diabetes Mellitus/physiopathology
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Prediabetic State/complications
• Retrospective Studies
• Risk Factors
• Wisconsin/epidemiology

• Colorectal Neoplasms/mortality
• Diabetes Mellitus, Type 2/mortality
• Female
• Humans
• Male
• Scotland/epidemiology

• Wellcome Trust