Lower Risk Of Colorectal Cancer Research Articles

Novel metabolomic predictors of incident colorectal cancer in men and women.

Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk. We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 NHS, 275 HPFS) incident CRC cases occurred and were matched 1:1 to controls. Liquid chromatography-mass spectrometry (LC-MS) identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis (MSEA) was used to identify differential abundance in metabolite classes. Weighted Correlation Network Analysis (WGCNA) provided modules of covarying metabolites, which were tested for CRC association. MSEA identified specific acylcarnitines associated with higher CRC risk and triacylglycerols with lower CRC risk among women and men. Further, phosphatidylcholines were associated with a higher risk of CRC among men. In an analysis restricted to CRC cases diagnosed two years after blood draw, myristoleic acid (OR = 1.37; 95%CI = 1.15-1.62; FDR = 0.072) and C60:12 triacylglycerol (OR = 0.75; 95%CI = 0.64-0.88; FDR = 0.072 were associated with CRC risk in women. WGCNA identified amino acids associated with CRC in men, fatty acid esters (carnitines) with distal CRC in men, and triradylcglycerols inversely associated with CRC in women. We identified pre-diagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.

Association of SGLT2 inhibitors with incident cancer

AimIt remains unknown whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be associated with incident cancer. MethodsWe analyzed individuals having diabetes and newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of cancer. A propensity score matching algorithm was employed to compare the subsequent development of cancer between the SGLT2i and DPP4i groups. ResultsAfter 1:2 propensity score matching, 26,823 individuals (8,941 SGLT2i, 17,882 DPP4i) were analyzed. During the mean follow-up duration of 2.0 ± 1.6 years, 1,076 individuals developed cancer. SGLT2i administration was associated with a reduced risk of cancer (HR 0.80, 95 % CI 0.70–0.91). Particularly, SGLT2i administration was related to a lower risk of colorectal cancer (HR 0.71, 95 % CI 0.50–0.998). Our primary findings remained consistent across various sensitivity analyses, including overlap weighting analysis (HR 0.79, 95 % CI 0.66–0.94), inverse probability of treatment weighting 0.75 (95 % CI 0.65–0.86), and induction period settings 0.78 (95 % CI 0.65–0.93). The risk of developing cancer was comparable among individual SGLT2is (P-value of 0.1738). ConclusionOur investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of cancer in individuals with diabetes.

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use

BackgroundSurveillance colonoscopy after polyp removal is recommended to prevent subsequent colorectal cancer (CRC). It is known that advanced adenomas have a substantially higher risk than non-advanced ones, but optimal intervals...

Associations of minerals intake with colorectal cancer risk in the prostate, lung, colorectal, ovarian cancer screening trial.

Exploring the association between common mineral intake and the risk of colorectal cancer (CRC). We utilized the multivariate Cox proportional hazards model to assess the association between intake of minerals and the risk of CRC, estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 101,686 eligible participants were included in the analysis of this study, including 1,100 CRC cases. After adjusting for potential confounders, we found that total zinc intake (HRQ4vs.Q1: 0.79, 95%CI 0.67-0.93; P for trend <0.05), iron intake (HRQ4vs.Q1: 0.81, 95%CI 0.68-0.96; P for trend <0.05), copper intake (HRQ4vs.Q1: 0.80, 95%CI 0.68-0.95; P for trend <0.05), selenium intake (HRQ4vs.Q1: 0.83, 95%CI 0.69-0.98; P for trend <0.05) were significantly negatively associated with the incidence of CRC, but magnesium intake in the appropriate range is associated with a reduced risk of CRC (HRQ3vs.Q1: 0.77, 95%CI 0.65-0.91; P for trend >0.05). Our findings suggested that an appropriate intake of total zinc, iron, copper, selenium and magnesium were associated with lower CRC risk.

A higher dietary alpha-linolenic acid intake is associated with lower colorectal cancer risk based on MUC4 rs2246901 variant among Korean adults

Alpha-linolenic acid (C18:3n-3 [ALA]) intake may have a beneficial effect in reducing cancer risk; however, its association with colorectal cancer (CRC) risk remains conflicted. Additionally, ALA was emphasized as being associated with mucins, an important glycoproteins family within the intestine. Thus, we hypothesized that a higher dietary ALA intake may reduce the risk of CRC and this preventive effect has an interaction with mucin 4 (MUC4) rs2246901. We conducted a case-control study at the National Cancer Center in Korea, involving 1039 cases and 1982 controls, aiming to determine the interaction of the MUC4 rs2246901 polymorphism and ALA intake in CRC risk. Dietary ALA intake was collected via semiquantitative food frequency questionnaire (SQFFQ), categorizing by 4 quartiles. We evaluated the odds ratios (ORs) and 95% confidence intervals (CIs) through unconditional logistic regression models. Higher dietary ALA intake was found to be inversely associated with CRC risk (adjusted OR = 0.58; 95% CI, 0.45–0.75, P for trend < .001). No significant association between MUC4 rs2246901 polymorphism and CRC risk was found. In a recessive model, MUC4 rs2246901 seemed to modify this association; participants with at least 1 major allele and higher ALA intake had a significantly lower CRC risk than those who had a lower intake (adjusted OR = 0.56; 95% CI, 0.43–0.72; P interaction = .047). A higher dietary ALA was proposed as a potential protective nutrient against CRC. Moreover, this association might be influenced by presence of the MUC4 rs2246901 polymorphism.

Adherence to the Mediterranean Diet and Colorectal Cancer Risk Among Moroccan Population: Hospital-Based Case Control Study.

Colorectal cancer (CRC) is a significant public health problem, including Morocco. The Mediterranean Diet (MD) has demonstrated potential anticancerogenic effects toward CRC in Northern Mediterranean countries. Using a Modified Mediterranean Diet (MMD) score adapted to southern countries, we investigated the relationship between adherence to the MD and the risk of CRC among the Moroccan population. During the study, we recruited 395 cases matched with 395 controls by sex and age (± 3 years). Using an adapted Food Frequency Questionnaire, we assessed the dietary intakes of participants to calculate the MMD score. We estimated the odds ratio and 95% confidence interval for both basic and adjusted models to evaluate the relationship between adherence to the MD and the risk of CRC. We observed a significant inverse association between adherence to the MD and CRC risk. In the adjusted model, moderate adherence to the MD was associated with 52% lower risk of CRC [odds ratio (OR*): 0.48 and 95% confidence interval (95% CI): 0.37-0.69], while high adherence to the MD was associated with 61% lower risk of CRC compared to the lowest category. When stratified by sex, both moderate [OR*: 0.36 (CI95%: 0.27-0.55)] and high [OR*: 0.43 (CI95%:0.27-0.74)] adherence were inversely correlated with CRC risk for women, while for men, only high adherence was inversely correlated with the risk of CRC [OR*: 0.3 (CI95%:0.19-0.5)]. Adherence to MD is associated with a decreased risk of CRC, an association that may be influenced by tumor location, sex, and age. Despite certain differences between northern and southern countries, the MD can be an effective preventative measure against CRC for populations in the Southern Mediterranean region.

Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The MOCCAS Study.

Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA) model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. gov, Number: NCT02715141.

Causality between six psychiatric disorders and digestive tract cancers risk: a two-sample Mendelian randomization study

Associations between psychiatric disorders and digestive tract cancers have been proposed. However, the causal link between these factors remains unclear. This study pioneers Mendelian randomization (MR) analysis to explore the genetic link between psychiatric disorders and digestive tract cancers risk. We analysed data on six psychiatric disorders [schizophrenia, bipolar disorder, major depressive disorder (MDD), attention deficit hyperactivity disorder, autism spectrum disorder, and panic disorder (PD)] and digestive tract cancers [esophagus cancer (EC), gastric cancer (GC), and colorectal cancer (CRC)] from genome-wide association studies databases. Using instrumental variables identified from significant single nucleotide polymorphism associations, we employed the inverse variance weighted (IVW) method alongside the weighted median (WM) method and MR-Egger regression. The results revealed no causal link between psychiatric disorders and the risk of EC or GC. Psychiatric disorders were not identified as risk factors for CRC. Notably, PD demonstrated a lower CRC risk (OR = 0.79, 95% CI 0.66–0.93, P = 0.01). This MR analysis underscores the lack of a causal association between psychiatric disorders and digestive tract cancers risk while suggesting a potential protective effect of PD against CRC.

Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study

ObjectiveWhether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain.DesignPatients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic...

A self-reported symptom-based decision-making model helps to rule out outpatient cases at low risk for CRC before colonoscopy

ObjectivesEffective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios. MethodsIn total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers. A decision-making model was constructed using 60 self-reported symptom parameters collected from the questionnaire. Further internal and external validation cohorts were built to evaluate the discriminatory power of the CRC model. The discriminatory power of the CRC model was assessed by the C-index and calibration plot. After that, the clinical utility and user experience of the CRC model were evaluated. ResultsNine symptom parameters were identified as valuable predictors used for modeling. Internal and external validation cohorts verified the adequate discriminatory power of the CRC model. In the clinical application step, all 17 physicians found the model easy to grasp, 99.9 % of the patients were satisfied with the survey form. Application of this model detected all CRC cases. The total consistency ratio of outpatient cases undergoing colonoscopy was 81.4 %. None of the low-risk patients defined by the CRC model had been diagnosed with CRC. ConclusionThis multicenter study developed and validated a simple and user-friendly decision-making model covering self-reported information. The CRC model has been demonstrated to perform well in terms of rapid outpatient decision-making scenarios and clinical utility, particularly because it can better rule out low-risk outpatient cases.

Integrative network analysis of transcriptomics data reveals potential prognostic biomarkers for colorectalcancer.

Cross-talk among biological pathways is essential for normal biological function and plays a significant role in cancer progression. Through integrated network analysis, this study explores the significance of pathway cross-talk in colorectal cancer (CRC) development at both the pathway and gene levels. In this study, we integrated the gene expression data with domain knowledge to construct state-dependent pathway cross-talk networks. The significance of the genes involved in pathway cross-talk was assessed by analyzing their association with cancer hallmarks, disease-gene relation, genetic alterations, and survival analysis. We also analyzed the gene regulatory network to identify the dysregulated genes and their role in CRC progression. Cross-talk was observed between immune-related pathways and pathways associated with cell communication and signaling. The PTPRC gene was identified as a mediator, facilitating interactions within the immune system and other signaling pathways. The rewired interactions of ITGA7 were identified as influential in the epithelial-mesenchymal transition in CRC. This study also highlighted the crucial link between cell communication and vascular smooth muscle contraction pathway in CRC progression. The survival analysis of identified gene clusters showed their significant prognostic value in distinguishing high-risk from low-risk CRC groups, and L1000CDS2 revealed seven potential drug molecules in CRC. Nine dysregulated genes (CTNNB1, EP300, JUN, MYC, NFKB1, RELA, SP1, STAT1, and TP53) emerge as transcription factors acting as common regulators across various pathways. This study highlights the crucial role of pathway cross-talk in CRC progression and identified the potential prognostic biomarkers and potential drug molecules.

The effects of ANRIL polymorphisms on colorectal cancer, tumor stage, and tumor grade among Iranian population.

Colorectal cancer (CRC) is a type of neoplasm, developing in the colon or rectum. The exact etiology of CRC is not well known, but the role of genetic, epigenetic, and environmental factors are established in its pathogenesis. Therefore, the aim of this research was to explore the effects of ANRIL polymorphisms on the CRC and its clinical findings. The peripheral blood specimens were collected from 142 CRC patients and 225 controls referred to Milad Hospital, Tehran, Iran. PCR- RFLP method was used to analyze ANRIL rs1333040, rs10757274 rs4977574, and rs1333048 polymorphisms. The ANRIL rs1333040 polymorphism was related to a higher risk of CRC in the co-dominant, dominant, and log-additive models. ANRIL rs10757274, rs4977574, and rs1333048 polymorphisms showed no effect on CRC susceptibility. The CGAA and TGGA haplotypes of ANRIL rs1333040/ rs10757274/ rs4977574/rs1333048 polymorphisms were associated with the higher and the lower risk of CRC respectively. The rs1333040 polymorphism was associated with higher TNM stages (III and IV). The frequency of ANRIL rs10757274 polymorphism was lower in CRC patients over 50 years of age only in the dominant model. In addition, the rs10757274 was associated with well differentiation in CRC patients. The ANRIL rs1333040 polymorphism was associated with a higher risk of CRC and higher TNM stages. ANRIL rs10757274 polymorphism was associated with the well-differentiated tumor in CRC.

Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

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.

Sex-specific associations of empirically derived dietary patterns with colorectal cancer risk in a Korean population: a case‒control study

Dietary patterns may be a crucial modifiable factor in colorectal cancer (CRC) risk. This study aimed to examine the associations of dietary patterns derived from two methods with CRC risk in Korea. In a study of 1420 CRC patients and 2840 control participants, we obtained dietary patterns by principal component analysis (PCA) and reduced rank regression (RRR) using 33 predefined food groups. The associations between dietary patterns and CRC risk were assessed using unconditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We identified two similar dietary patterns, derived from PCA 1 (prudent) and RRR (healthy), characterized by higher consumption of green/yellow vegetables, light-colored vegetables, fruits, eggs, and milk in both men and women. In women, higher prudent and healthy pattern scores were significantly associated with a lower risk of CRC (prudent, ORQ4 vs. Q1 = 0.59, 95% CI 0.40–0.86, P for trend = 0.005; healthy, ORQ4 vs. Q1 = 0.62, 95% CI 0.43–0.89, P for trend = 0.007). In men, a significant inverse association between dietary pattern and risk of rectal cancer was found only for the healthy dietary pattern (ORQ4 vs. Q1 = 0.66, 95% CI 0.45–0.97, P for trend = 0.036). Compared with the dietary pattern derived by PCA, the RRR dietary pattern had a slightly stronger association with a lower risk of distal colon cancer (ORQ4 vs. Q1 = 0.58, 95% CI 0.35–0.97, P for trend = 0.025) and rectal cancer (ORQ4 vs. Q1 = 0.29, 95% CI 0.15–0.57, P for trend < 0.001) in women. Our findings suggest cancer prevention strategies focusing on a diet rich in vegetables, fruits, eggs, and milk. Moreover, the use of both PCA and RRR methods may be advantageous to explore the associations between dietary patterns and risk of CRC.

Interactions between vitamin B2, the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms, and colorectal cancer risk in a Korean population.

We explored whether the association between vitamin B2 and colorectal cancer (CRC) risk could be modified by the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms and examined whether the interaction effects are sex-specific. We performed a case-control study involving 1,420 CRC patients and 2,840 controls from the Korea National Cancer Center. Dietary vitamin B2 intake was assessed using a semiquantitative food frequency questionnaire, and the association with CRC was evaluated. Genotyping was performed using an Illumina MEGA-Expanded Array. For gene-nutrient interaction analysis, pre-matched (1,081 patients and 2,025 controls) and matched (1,081 patients and 1,081 controls) subsets were included. Unconditional and conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A higher intake of vitamin B2 was associated with a significantly lower CRC risk (OR, 0.65; 95% CI, 0.51 to 0.82; p<0.001). Carriers of at least 1 minor allele of MTRR rs1801394 showed a significantly higher CRC risk (OR, 1.43; 95% CI, 1.12 to 1.83). Males homozygous for the major allele (A) of MTRR rs1801394 and who had a higher intake of vitamin B2 had a significantly lower CRC risk (OR, 0.31; 95% CI, 0.18 to 0.54; p-interaction=0.02). In MTR rs1805087, males homozygous for the major allele (A) and who had a higher vitamin B2 intake had a significantly lower CRC risk (OR, 0.38; 95% CI, 0.25 to 0.60; p-interaction<0.001). The MTRR rs1801394 and MTR rs1805087 genetic polymorphisms may modify the association between vitamin B2 and CRC risk, particularly in males. However, further studies are warranted to confirm these interaction results.

Construction of an immune predictive model and identification of TRIP6 as a prognostic marker and therapeutic target of CRC by integration of single-cell and bulk RNA-seq data

BackgroundInvestigations elucidating the complex immunological mechanisms involved in colorectal cancer (CRC) and accurately predicting patient outcomes via bulk RNA-Seq analysis have been notably limited. This study aimed to identify the immune status of CRC patients, construct a prognostic model, and identify prognostic signatures via bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq).MethodsThe scRNA-seq data of CRC were downloaded from Gene Expression Omnibus (GEO). The UCSC Xena database was used to obtain bulk RNA-seq data. Differentially expressed gene (DEG), functional enrichment, and random forest analyses were conducted in order to identify core genes associated with colorectal cancer (CRC) that were relevant to prognosis. A molecular immune prediction model was developed using logistic regression after screening features using the least absolute shrinkage and selection operator (LASSO). The differences in immune cell infiltration, mutation, chemotherapeutic drug sensitivity, cellular senescence, and communication between patients who were at high and low risk of CRC according to the predictive model were investigated. The prognostic genes that were closely associated with CRC were identified by random survival forest (RSF) analysis. The expression levels and clinical significance of the hub genes were analyzed in vitro. The LoVo cell line was employed to ascertain the biological role of thyroid hormone receptor-interacting protein 6 (TRIP6).ResultsA total of seven main cell subtypes were identified by scRNA-seq analysis. A molecular immune predictive model was constructed based on the risk scores. The risk score was significantly associated with OS, stage, mutation burden, immune cell infiltration, response to immunotherapy, key pathways, and cell–cell communication. The functions of the six hub genes were determined and further utilized to establish a regulatory network. Our findings unequivocally confirmed that TRIP6 upregulation was verified in the CRC samples. After knocking down TRIP6, cell proliferation, migration, and invasion of LoVo cells were inhibited, and apoptosis was promoted.ConclusionsThe molecular predictive model reliably distinguished the immune status of CRC patients. We further revealed that TRIP6 may act as an oncogene in CRC, making it a promising candidate for targeted therapy and as a prognostic marker for CRC.

Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)

BackgroundAltered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. MethodsIn a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1,591 incident colorectal cancer cases (55% women) and 1,591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FindingsOf the 97 assayed lipids, 24 were inversely associated (nominally p<0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95%CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95%CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding cases diagnosed <5 years after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. InterpretationElevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. FundingWorld Cancer Research Fund (reference:2013/1002); European Commission (FP7: BBMRI-LPC; reference:313010).

The interaction between magnesium intake, the genetic variant INSR rs1799817 and colorectal cancer risk in a Korean population: a case-control study

Magnesium may have a significant impact on the development of cancer. However, the relationship between magnesium intake and the risk of colorectal cancer (CRC) is unclear. Therefore, we evaluated the association between magnesium intake and the risk of CRC, and we investigated how the insulin receptor (INSR) rs1799817 variant impacts this relationship. Data from 1,420 CRC patients and 2,840 controls from the Korean National Cancer Centre were analysed. A higher intake of magnesium was associated with a reduced risk of CRC in the total population (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52–0.81). We found that G + carriers of INSR rs1799817 with higher magnesium intake had a significantly lower risk of CRC (p for interaction = 0.003). Our findings indicated that high magnesium intake could be associated with a decreased risk of CRC, and this association could be modified by the INSR rs1799817 variant.