Risk Of Adenomas Research Articles

Being Breastfed in Infancy and Risk of Colorectal Cancer and Precursor Lesions

Emerging evidence implicates the importance of perinatal and early-life exposures in colorectal cancer (CRC) development. However, it remains unclear whether being breastfed in infancy is associated with CRC risk in adult life, particularly early adulthood. We prospectively investigated the association between history of being breastfed and risk of CRC and its precursor lesions among 66,634 women 46-93 years of age from the Nurses' Health Study and 92,062 women 27-68 years of age from the Nurses' Health Study II. Cox regression and logistic regression for clustered data were used to estimate hazard ratios for CRC and odds ratios for CRC precursors, respectively. During 3.5 million person-years of follow-up, we identified 1490 incident cases of CRC in 2 cohorts. Having been breastfed was associated with a 23% (95% confidence interval [CI], 10% to 38%) increased risk of CRC. The risk of CRC increased with duration of being breastfed (Ptrend < .001). These findings were validated using breastfeeding information from the mothers of a subset of participants. Among younger participants from the Nurses' Health Study II, a significant association was observed between being breastfed and increased risk of high-risk adenomas under 50 years of age (odds ratio, 1.46; 95% CI, 1.16 to 1.83). Consistently, having been breastfed was associated with increased risk of CRC among participants ≤55 years of age (hazard ratio, 1.38; 95% CI, 1.06 to 1.80). Being breastfed in infancy was associated with increased risk of CRC in adulthood, including among younger adults. However, further research is needed to understand the underlying biological mechanisms, as this association does not establish causation.

Older Age at First Screening Colonoscopy is Associated With an Increased Risk of Colorectal Adenomas and Cancer.

The goal of colorectal cancer (CRC) screening is to detect precancerous polyps before cancer development or identification of cancer at an early stage. Guidelines have recommended screening colonoscopy to start at age 45. Our aim was to determine the impact of delays in performing the first screening colonoscopy on the risk of adenoma or CRC detection. We analyzed colonoscopy and histopathology data of average CRC risk patients who had their first screening colonoscopy between 2010 and 2017. Univariate and multivariable logistic regression was performed to determine the association between demographic variables and the risk of adenomas or CRC. A total of 1155 average risk patients underwent their initial screening colonoscopy during the study period. Median age was 54 years (range of 45-87) and 58.2% were females. In multivariable analysis, older age at first screening colonoscopy was significantly associated with the detection of adenomatous polyps (odds ratio 1.05, 95% confidence interval 1.04-1.07, P<0.001) and CRC (odds ratio 1.11, 95% confidence interval 1.06-1.16, P<0.001). The association between age and risk of adenomatous polyps (F-test 35.43, P=0.0019) and CRC (F-test 36.94, P=0.0017) fit an exponential growth model. It was estimated that the detection rate doubled every 14.20 years and 4.75 years for adenomas and CRC, respectively. We found that older age at the initial performance of a screening colonoscopy was associated with increased detection of adenomatous polyps and CRC. This work highlights the need for guideline adherence for the prevention of CRC development.

Statin use and risk of colorectal cancer in patients with inflammatory bowel disease

Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive. From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD),-8.0 (95% CIs:-15.8 to-0.2 per 10,000 person-years); aHR=0.76 (95% CIs: 0.61 to 0.96)). The benefit for incident CRC was duration-dependent in a nested case-control design: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 (0.25 to 1.43) for 1 to <2 years of use, 0.46 (0.21 to 0.98) for 2 to <5 years of use, and 0.38 (0.16 to 0.86) for ≥5 years of use (Pfor tread=0.016). Compared with non-statin users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9; RD,-5.9 (-10.5 to-1.2); aHR, 0.56 (0.37 to 0.83)) and all-cause mortality (IR: 156.4 vs. 231.4; RD,-75.0 (-96.6 to-53.4); aHR, 0.63 (0.57 to 0.69)). Statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The benefit for incident CRC was duration-dependent, with a significantly lower risk after ≥2 years of statin use. This research was supported by Forte (i.e., the Swedish Research Council for Health, Working Life and Welfare).

Association between sulfur microbial diet and the risk of colorectal cancer precursors in older adults.

Sulfur microbial diet (SMD), related to the enrichment of sulfur-metabolizing gut bacteria, has been confirmed to be linked to an elevated risk of early-onset colorectal adenoma in young females. However, it remains unclear whether SMD is associated with the risk of colorectal adenoma in older people, who are at greater risk for colorectal cancer. All data on participants in this study were retrieved from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening test. Participants' adherence to this dietary pattern was assessed using SMD score. Hazard ratios (HR) and 95% confidence intervals (CI) were adopted in Cox proportional hazards regression models to assess the link between SMD score and the incidence of colorectal adenoma in participants included in the study. Specific stratified analyses were constructed to assess whether this association changed in different conditions, whereas the robustness of the association was examined through sensitivity analyses. The mean baseline age of participants was 62.1 (SD 5.2) years (range 54.0-75.0 years). During 19,468,589 person-years of follow-up, 992 colorectal adenoma cases were documented in a total of 17,627 included participants. In a fully adjusted model, an increased risk of colorectal adenoma was determined in participants in the highest quartile of SMD score in comparison with those in the lowest quartile (HRquartile4 vs. HRquartile1 = 1.23; 95% CI: 1.02, 1.47; p = 0.017 for trend). This positive association between SMD score and adenoma risk was more evident in participants who were current or former smokers (p = 0.029 for interaction). In this study, our results support a role for the SMD in the carcinogenicity of colorectal cancer precursors among older adults. Nevertheless, these results require validation through more research.

A bioinformatics analysis of potential cellular communication networks in non-alcoholic steatohepatitis and colorectal adenoma using scRNA-seq and bulk-seq.

Non-alcoholic fatty liver disease (NAFLD) is the global most common chronic liver disease. Non-alcoholic steatohepatitis (NASH), an inflammatory subtype of NAFLD, has been shown to significantly increase the risk of colorectal adenoma (CRA). Therefore, from the perspective of bioinformatics analysis, the potential mechanisms of NASH/NAFLD-CRA can be explored. In this study, we screened the differentially expressed genes (DEGs) and core effect pathways between NASH and CRA by analyzing the single-cell data of CRA patients and the high-throughput sequencing data (GSE37364 and GSE89632) in the online database. We screened therapeutic targets and biomarkers through gene function classification, pathway enrichment analysis, and protein-protein interaction network analysis. In terms of single cell data, we screened the core effect pathway and specific signal pathway of cell communication through cell annotation and cell communication analyses. The purpose of the study was to find potential biomarkers, therapeutic targets, and related effect pathways of NASH-CRA. NASH-CRA comorbidities were concentrated in inflammatory regulation-related pathways, and the core genes of disease progression included IL1B, FOSL1, EGR1, MYC, PTGS2, and FOS. The results suggested the key pathway of NASH-CRA might be the WNT pathway. The main cell signal communication pathways included WNT2B - (FZD6 + LRP5) and WNT2B - (FZD6 + LRP6). The send-receive process occurred in embryonic stem cells. The core genes of NASH-CRA (FOS, EGR1, MYC, PTGS2, FOSL1, and IL1B) may participate in inflammation and immune responses through up-regulation in the process of disease occurrence, interfering with the pathophysiological process of CRA and NASH. NASH-CRA produces cell signal communication in the WNT pathway sent by WNT2B and received by FZD6, LRP5, and LRP6 in embryonic stem cells. These findings may help formulate early diagnosis and treatment strategies for CRA in NAFLD/NASH patients, and further explore corresponding prognostic markers and potential approaches. The significance of scRNA-seq in exploring tumor heterogeneity lies in promoting our understanding of the expression program of tumor related genes in tumor development patterns. However, the biggest challenge is that this analysis may miss out on some biologically significant gene expression programs.

Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes.

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted.

The Association Between Helicobacter pylori Infection With Different Types of Colon Cancer and Children’s Diseases: An Overview of Meta-analyses

Objectives: Helicobacter pylori is a gram-negative curved bacillus that assumes a significant role in colon cancer and children´s diseases. This study aimed to examine the association between H. pylori infection with colon cancer and children´s diseases in order to achieve a comprehensive understanding of these associations and for future works. Methods: Three main databases (i.e., Cochrane Central Register of Controlled Trials [CENTRAL], Scopus, and MEDLINE) were systematically searched by two reviewers from their inception date to 2022 in order to determine the association between the H. pylori infection with the colon cancer and children’s diseases. Results: The findings of two meta-analyses were similar regarding the positive association between the risks of colorectal neoplasm (pooled OR=0.18; 95% CI of 0.99–1.40; P&gt;0.05) and colon neoplasia (pooled OR=0.41; 95% confidence interval 1.24–1.60; P=0.000). H. pylori was associated with an increased risk of colorectal adenoma, adenocarcinoma, and advanced adenoma. Also H. pylori infection was correlated with a high risk of iron deficiency anemia (IDA), otitis media with effusion (OME), Henoch-Schonlein purpura, and growth disorders in children. Conclusions: In sum, the H. pylori infection may have been associated with an increased risk of colorectal cancer and children’s diseases.

Gut Microbiota Enterotypes Mediate the Effects of Dietary Patterns on Colorectal Neoplasm Risk in a Chinese Population.

Colorectal cancer (CRC) risk is influenced by dietary patterns and gut microbiota enterotypes. However, the interaction between these factors remains unclear. This study examines this relationship, hypothesizing that different diets may affect colorectal tumor risk in individuals with varied gut microbiota enterotypes. We conducted a case-control study involving 410 Han Chinese individuals, using exploratory structural equation modeling to identify two dietary patterns, and a Dirichlet multinomial mixture model to classify 250 colorectal neoplasm cases into three gut microbiota enterotypes. We assessed the association between dietary patterns and the risk of each tumor subtype using logistic regression analysis. We found that a healthy diet, rich in vegetables, fruits, milk, and yogurt, lowers CRC risk, particularly in individuals with type I (dominated by Bacteroides and Lachnoclostridium) and type II (dominated by Bacteroides and Faecalibacterium) gut microbiota enterotypes, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] = 0.48-0.89) and 0.42 (95% CI = 0.29-0.62), respectively. Fruit consumption was the main contributor to this protective effect. No association was found between a healthy dietary pattern and colorectal adenoma risk or between a high-fat diet and colorectal neoplasm risk. Different CRC subtypes associated with gut microbiota enterotypes displayed unique microbial compositions and functions. Our study suggests that specific gut microbiota enterotypes can modulate the effects of diet on CRC risk, offering new perspectives on the relationship between diet, gut microbiota, and colorectal neoplasm risk.

Associations of Dietary Patterns with Colorectal Adenomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Cohort.

Most colorectal cancers arise from adenomas, and although insulinemic and inflammatory dietary patterns have been associated with colorectal cancer risk, these dietary patterns have not been studied in relation to adenoma risk. Using data from 21,192 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening cohort, we calculated the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP), and overall dietary quality measured via the Healthy Eating Index (HEI-2015), from food frequency questionnaires (FFQ). In multivariable-adjusted logistic regression, we investigated associations of these dietary indices with adenoma (any adenoma, advanced adenoma, n = 19,493) and recurrent adenoma (n = 1,699). EDIH was not associated with adenoma or advanced adenoma but was marginally associated with recurrent adenoma. The OR (95% CI) comparing highest (lowest insulinemic) versus lowest (most hyperinsulinemic) quintiles was 0.76 (0.55-1.05) after multivariable adjustment including BMI. EDIP and HEI-2015 were not associated with any of the three outcomes. In the PLCO cohort, we did not observe substantial associations between dietary patterns and risk of colorectal adenomas. Pending confirmation in larger prospective studies, our findings suggest that these dietary patterns may not substantially affect colorectal cancer risk via the adenoma-carcinoma sequence.

Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome

BackgroundPolygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary...

Association between Sleep Duration and Colorectal Adenomas: Findings from a Case-Control Study in Vietnam.

Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population. We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders. Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12-1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14-2.18) and males (OR, 1.45; 95% CI, 1.08-1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09-2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19-2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese. Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population. Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control.

Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas.

Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent adenomas. Better methods to evaluate who benefits from increased surveillance are needed. We evaluated the use of altered EVL methylation as a potential biomarker for risk of recurrent adenomas. Patients with ≥1 colonoscopy had EVL methylation (mEVL) measured with an ultra-accurate methylation-specific droplet digital PCR assay on normal colon mucosa. The association between EVL methylation levels and adenoma or colorectal cancer was evaluated using three case/control definitions in three models: unadjusted (model 1), adjusting for baseline characteristics (model 2), and an adjusted model excluding patients with colorectal cancer at baseline (model 3). Between 2001 and 2020, 136 patients were included; 74 healthy patients and 62 patients with a history of colorectal cancer. Older age, never smoking, and baseline colorectal cancer were associated with higher levels of mEVL (P ≤ 0.05). Each log base 10 difference in mEVL was associated with an increased risk of adenoma(s) or cancer at/after baseline for model 1 [OR, 2.64; 95% confidence interval (CI), 1.09-6.36], and adenoma(s) or cancer after baseline for models 1 (OR, 2.01; 95% CI, 1.04-3.90) and model 2 (OR, 3.17; 95% CI, 1.30-7.72). Our results suggest that EVL methylation level detected in the normal colon mucosa has the potential to be a biomarker for monitoring the risk for recurrent adenomas. These findings support the potential utility of EVL methylation for improving the accuracy for assigning risk for recurrent colorectal adenomas and cancer.

Mutual association between family history of gastric and colorectal cancer and risk of gastric and colorectal cancer.

We evaluated the associations between gastric cancer (GC) family history (FH) and colorectal cancer (CRC) risk and between CRC FH and GC/gastric adenoma risk. We used data of participants who underwent national cancer screening between 2013 and 2014. Participants with GC or CRC FH in first-degree relatives (n=1 172 750) and those without cancer FH (n=3 518 250) were matched 1:3 by age and gender. Of the 1 172 750 participants with a FH, 871 104, 264 040, and 37 606 had FHs of only GC, only CRC, and both GC and CRC, respectively. The median follow-up time was 4.8years. GC and CRC FHs were associated with increased GC and CRC risks, respectively. GC FH was associated with CRC risk (adjusted hazard ratio 1.05; 95% confidence interval [CI] 1.01-1.10), whereas CRC FH was not associated with the risk of GC or gastric adenoma. However, gastric adenoma risk increased 1.62-fold (95% CI 1.40-1.87) in participants with FHs of both GC and CRC, demonstrating a significant difference with the 1.39-fold (95% CI 1.34-1.44) increase in participants with only GC FH. Furthermore, GC risk increased by 5.32 times (95% CI 1.74-16.24) in participants with FHs of both GC and CRC in both parents and siblings. GC FH was significantly associated with a 5% increase in CRC risk. Although CRC FH did not increase GC risk, FH of both GC and CRC further increased the risk of gastric adenoma. FHs of GC and CRC may affect each other's neoplastic lesion risk.

Endoscopic features of lymphoid follicles in the colonic mucosa using the image enhanced endoscopy and its association with colorectal adenoma.

Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86). LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma.

Field Synopsis of Environmental and Genetic Risk Factors of Sporadic Early-Onset Colorectal Cancer and Advanced Adenoma.

To systematically appraise and synthesize available epidemiologic evidence on the associations of environmental and genetic factors with the risk of sporadic early-onset colorectal cancer (EOCRC) and early-onset advanced colorectal adenoma (EOCRA). Multiple databases were comprehensively searched to identify eligible observational studies. Genotype data from UK Biobank were incorporated to examine their associations with EOCRC in a nested case-control design. Meta-analyses of environmental risk factors were performed, and the strength of evidence was graded based on predefined criteria. Meta-analyses of genetic associations were conducted using the allelic, recessive, and dominant models, respectively. A total of 61 studies were included, reporting 120 environmental factors and 62 genetic variants. We found 12 risk factors (current overweight, overweight in adolescence, high waist circumference, smoking, alcohol, sugary beverages intake, sedentary behavior, red meat intake, family history of colorectal cancer, hypertension, hyperlipidemia, and metabolic syndrome) and three protective factors (vitamin D, folate, and calcium intake) for EOCRC or EOCRA. No significant associations between the examined genetic variants and EOCRC risk were observed. Recent data indicate that the changing patterns of traditional colorectal cancer risk factors may explain the rising incidence of EOCRC. However, research on novel risk factors for EOCRC is limited; therefore, we cannot rule out the possibility of EOCRC having different risk factors than late-onset colorectal cancer (LOCRC). The potential for the identified risk factors to enhance the identification of at-risk groups for personalized EOCRC screening and prevention and for the prediction of EOCRC risk should be comprehensively addressed by future studies.

Garlic consumption in relation to colorectal cancer risk and to alterations of blood bacterial DNA

PurposeGarlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood.MethodsWe conducted a case–control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann–Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence.ResultsThe OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11–0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus.ConclusionsThe study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.

Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma

BackgroundIn recent years, morbidity and mortality from colorectal cancer have increased. Colorectal adenoma is the main precancerous lesion. Understanding the pathogenesis of colorectal adenoma will help to improve the early diagnosis rate of colorectal cancer.MethodsIn this case–control study, we focused on three single nucleotide polymorphisms (SNPs) in genes SLC8A1 (rs4952490), KCNJ1 (rs2855798), and SLC12A1 (rs1531916). We analyzed 207 colorectal adenoma patients (112 high-risk cases and 95 low-risk cases) and 212 control subjects by Sanger sequencing. A food frequency questionnaire (FFQ) was used to survey demographic characteristics and dietary nutrition.ResultsIn the overall analysis, the results suggested that the AA+AG and AG genotype carriers of rs4952490 had a 73.1% and 78% lower risk of colorectal adenoma compared to GG genotype carriers, respectively. However rs2855798 and rs1531916 were not associated with the incidence of colorectal adenoma. Additionally, stratified analysis showed that rs4952490 AA+AG and AG genotypes had a protective effect against low-risk colorectal adenoma in patients aged ≤ 60 years old who were non-smokers. We also observed that when calcium intake was higher than 616 mg/d and patients carried at least one gene with variant alleles there was a protective effect against low-risk colorectal adenoma.ConclusionsInteractions between dietary calcium intake and calcium reabsorption genes may affect the occurrence and development of colorectal adenoma.

Opportunistic colonoscopy in healthy individuals: A non-trivial risk of adenoma.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Opportunistic colonoscopy may be beneficial in reducing the incidence of CRC by detecting its precursors. To determine the risk of colorectal adenomas in a population who underwent opportunistic colonoscopy, and demonstrate the need for opportunistic colonoscopy. A questionnaire was distributed to patients who underwent colonoscopy in the First Affiliated Hospital of Zhejiang Chinese Medical University from December 2021 to January 2022. The patients were divided into two groups, the opportunistic colonoscopy group who underwent a health examination including colonoscopy without intestinal symptoms due to other diseases, and the non-opportunistic group. The risk of adenomas and influence factors were analyzed. Patients who underwent opportunistic colonoscopy had a similar risk to the non-opportunistic group, in terms of overall polyps (40.8% vs. 40.5%, P = 0.919), adenomas (25.8% vs. 27.6%, P = 0.581), advanced adenomas (8.7% vs. 8.6%, P = 0.902) and CRC (0.6% vs. 1.2%, P = 0.473). Patients with colorectal polyps and adenomas in the opportunistic colonoscopy group were younger (P = 0.004). There was no difference in the detection rate of polyps between patients who underwent colonoscopy as part of a health examination and those who underwent colonoscopy for other reasons. In patients with intestinal symptoms, abnormal intestinal motility and changes in stool characteristics were frequent (P = 0.014). The risk of overall colonic polyps, advanced adenomas in healthy people undergoing opportunistic colonoscopy no less than that in the patients with intestinal symptoms, positive FOBT, abnormal tumor markers, and who accepted re-colonoscopy after polypectomy. Our study indicates that more attention should be paid to the population without intestinal symptoms, especially smokers and those older than 40 years.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations throughout the life course and risk of colorectal cancer precursors.

Despite the increasing incidence in colorectal cancer (CRC) among the young population, the involvement of modifiable early-life exposures is understudied. We prospectively investigated the association of lifestyle score, which measures adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, in adolescence and adulthood with risk of CRC precursors in 34,509 women enrolled in the Nurses' Health Study II. Participants reported adolescent diet in 1998 and subsequently underwent at least one lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for clustered data. During follow-up (1998-2015), 3036 women had at least one adenoma, and 2660 had at least one serrated lesion. In multivariable analysis, per unit increase in adolescent WCRF/AICR lifestyle score was not associated with risk of total adenoma or serrated lesions, in contrast to adult WCRF/AICR lifestyle score (OR = 0.92, 95% CI: 0.87-0.97, Ptrend = 0.002 for total adenoma; and OR = 0.86, 95% CI: 0.81-0.92, Ptrend < 0.001 for total serrated lesions). Adherence to the 2018 WCRF/AICR recommendations during adulthood but not during adolescence was associated with a lower risk of CRC precursors.

Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis.

Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis. Summary-level data for gut microbiota and metabolites were obtained from MiBioGen, FINRISK and human metabolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively. Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (β = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gammaproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06×10-8), Enterobacteriaceae (β = 0.023, P = 1.29×10-5). We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colorectal cancer risk. This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.