Lower Risk Of Colorectal Cancer Research Articles

Association of dietary patterns derived by reduced-rank regression with colorectal cancer risk and mortality.

Unhealthy dietary patterns contribute to an increased risk of colorectal cancer (CRC). Limited prior research has used reduced rank regression (RRR) to assess dietary patterns relative to CRC risk. This study aimed to identify dietary patterns derived by RRR and assess their associations with CRC risk and mortality. We used data from the multicentre Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial. Dietary intake was assessed using a Dietary History Questionnaire. In the RRR intake of fibre, folate, and the percentage of energy from carbohydrates, saturated and unsaturated fatty acids were used as response variables. Cox models and competing risk survival regression, with age as the time scale, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk and mortality, respectively. The median follow-up time for CRC risk (n = 1044) and mortality (n = 499) was 9.4 years (Interquartile Range: 8. 0, 10.1) and 16.9 years (11.9, 18.6), respectively. Two dietary patterns were identified: the first was characterised by high carbohydrate, folate and low fatty acid intake, and the second by high fibre and unsaturated fatty acid. Compared to participants in the first tertile of the high fibre and unsaturated fatty acid pattern, those in the third tertile had a lower risk of CRC (HR = 0.88; 95% CI: 0.76, 1.03), and colon cancer (HR = 0.85; 95% CI: 0.72, 1.01). Conversely, the high carbohydrate, high folate and low fatty acid pattern had no association with CRC outcomes. None of the dietary patterns showed associations with rectal cancer or CRC mortality. A diet enriched with high fibre and unsaturated fatty acids may reduce the risk of CRC. These results highlight the potential protective effect of adequate fibre intake in conjunction with high consumption of unsaturated fatty acids against CRC.

Colorectal Cancer Incidence and Mortality After Negative Colonoscopy Screening Results

The current recommendation for a 10-year rescreening interval after a negative colonoscopy screening (NCS) result has been questioned, with some studies showing a persistently lower risk of colorectal cancer (CRC) after NCS results. To examine long-term CRC incidence and mortality after NCS results (ie, no presence of CRC or polyps) and according to a risk score based on major demographic and lifestyle risk factors. In this cohort study, 3 prospective US population-based cohorts from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study were followed up from 1988 and 1991 to 2020. Data from the National Health and Nutrition Examination Survey (NHANES) from the January 1, 2017, to December 31, 2018, cycle were used to compare the risk profile distribution with that of the general US population. Data analysis was performed from October 2023 to August 2024. Time-varying status of NCS results and risk score. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs for incidence and mortality of CRC. A total of 195 453 participants (median [IQR] age, 44 [37-56] years at baseline; 81% female) were followed up for a median (IQR) of 12 (6-20) years. Among 81 151 individuals with NCS results and 114 302 without endoscopy, 394 and 2229 CRC cases and 167 and 637 CRC deaths, respectively, were documented. Negative colonoscopy screening results were consistently associated with lower CRC incidence (HR, 0.51; 95% CI, 0.44-0.58) and mortality (HR, 0.56; 95% CI, 0.46-0.70) for 20 years. Among individuals with NCS results, those with an intermediate risk (scores, 6-7) and low risk (scores, 0-5) did not reach the 10-year cumulative incidence of CRC (0.78%) of the high-risk individuals (scores, 8-12) until 16 and 25 years after initial screening, respectively. These findings provide evidence for shared decision-making between patients and physicians to consider extending the rescreening intervals after an NCS result beyond the currently recommended 10 years, particularly for individuals with a low-risk profile. These results showed, as a proof of concepts, the importance of considering known CRC risk factors when making decisions for colonoscopy rescreening.

Polygenic risk score, healthy lifestyle score, and colorectal cancer risk: a prospective cohort study.

Both genetic factors and lifestyle play a critical role in colorectal cancer (CRC), but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unclear. We included 51,171 participants from the PLCO cohort. A polygenic risk score was created based on 205 genetic variants associated with CRC, and a healthy lifestyle score was constructed based on six lifestyle factors. Cox regression models were used to evaluate the association of genetic and lifestyle factors with CRC incidence. Compared with individuals at low genetic risk (the lowest 20%), those with intermediate genetic risk (20%-80%) and high genetic risk (the highest 20%) had a significantly increased risk of CRC (HR = 1.71 and 2.52, respectively). Compared with participants with a favorable lifestyle (scoring 4-6), those with an unfavorable lifestyle (scoring 0 or 1) had a 47% higher risk of CRC. Moreover, participants with a high genetic risk and a favorable lifestyle had a 45% lower risk of CRC than those with a high genetic risk and an unfavorable lifestyle, with their 10-year absolute risks of 1.29% and 2.07%, respectively. Our findings suggest that adherence to a healthy lifestyle holds promise to reduce the genetic impact on CRC risk. This study indicates that modifiable lifestyle play an important role in CRC prevention, providing new insights for personalized prevention strategies.

Association of low-carbohydrate diet score and carbohydrate quality index with colorectal cancer risk: a large-scale case-control study.

Carbohydrate intake has been linked to colorectal cancer (CRC) risk, with variations depending on the quantity and quality of carbohydrates consumed. This study aimed to investigate the association between carbohydrate quantity and quality, using the low-carbohydrate diet score (LCD) and carbohydrate quality index (CQI), and the risk of CRC in the Chinese population. We conducted a case-control study in Guangzhou, China, with 2,799 CRC cases and an equal number of sex- and age-matched controls. Dietary data were collected using a validated food frequency questionnaire to derive the LCD and CQI, assessing the quantity and quality of carbohydrate intake separately. Odds ratios (OR) and 95% confidence interval (CI) for CRC risk were estimated using unconditional logistic regression models, and restricted cubic splines were used to explore potential non-linear relationships. The results demonstrated that higher adherence to the overall LCD score, plant-based LCD score, and CQI was associated with a lower risk of CRC. The adjusted ORs (95%CIs) for the highest quintile of intake in comparison with the lowest quintile were 0.76 (0.63, 0.91) for the overall LCD score, 0.61 (0.50, 0.74) for the plant-based LCD score, and 0.70 (0.58,0.84) for the CQI, respectively. However, the animal-based LCD did not show a significant association with CRC risk, with the adjusted OR (95%CI) for the highest quintile compared to the lowest being 0.98 (0.81, 1.18). Restricted cubic splines analysis showed non-linear associations of the overall LCD score, animal-based LCD score, and plant-based LCD score with CRC risk. In contrast, a linear relationship was observed between CQI and CRC risk (Pnonlinear = 0.594). Our findings indicate that the overall LCD score, the plant-based LCD score, and the CQI were inversely associated with the risk of CRC.

The association between non- and pro-healthy diet indices and the risk of colorectal cancer: a case-control study

BackgroundThe Non-Healthy Diet Index (NHDI) and the Pro-Healthy Diet Index (PHDI) are two novel indices that evaluate the healthiness of a diet based on the consumption of several food groups. This study aimed to evaluate the association between adherence to the PHDI and NHDI and colorectal cancer (CRC) risk in the Iranian population.MethodsThe current study was conducted as a hospital-based research using a case (n = 71)- matched-controls (n = 142) design in Tehran, Iran. A semi-quantitative food frequency questionnaire was utilized to determine participants’ dietary intake after confirming the diagnosis of CRC and at the time of the interview. The PHDI-10 was employed to assess the consumption of foods with positive health effects, which is linked to the frequency of consuming 10 food groups, and the NHDI-14 was used to assess the consumption of foods that have detrimental effects on health, based on the frequency of 14 food groups. Logistic regression was used to evaluate the association between continuous PHDI and NHDI scores and their tertiles with CRC.ResultsThe results indicated that individuals in the highest tertile of the PHDI showed a lower CRC risk compared to those in the lowest tertile (adjusted model- odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.10–0.61; P = 0.002). Also, lower odds of CRC risk were seen with each unit change in the total score of PHDI in the adjusted model (OR = 0.86; 95% CI: 0.76–0.96; P = 0.009). In contrast, individuals in the highest tertile of the NHDI showed a higher risk of CRC compared to those in the lowest tertile (OR = 2.62; 95% CI: 1.09–6.27; P = 0.030) in the adjusted model. Also, higher odds of CRC risk were observed with each unit increase in the total score of NHDI in the adjusted model (OR = 1.13; 95% CI: 1.03–1.25; P = 0.008).ConclusionsThe present study showed that higher adherence to PHDI and NHDI is associated with lower and higher CRC risk, respectively. These results provide valuable insights into the roles of healthy and unhealthy diets in CRC prevention.

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...

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.

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.

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.