The global burden of gynecological diseases from 1990 to 2019.

INTRODUCTION: Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to estimate the disease burden of gynecological diseases and describe their trends in women of all ages from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we examined the incidence, disability-adjusted life years (DALYs) and deaths from gynecological diseases by age in 204 countries and territories worldwide from 1990 to 2019. Analyses were conducted in 2022. RESULTS: Globally, the age-standardized incidence rate (ASIR) and age-standardized DALY rate (ASDR) of gynecological diseases decreased by -0.176 % and -0.245 %, respectively from 1990 to 2019. Low socioeconomic development index (SDI) countries had the highest ASIR and ASDR in 2019. The age-specific incidence rate of gynecological diseases in women aged 15-29 years increased from 1990 to 2019, and the 20-24-year age group increased the greatest by 0.21%. Polycystic ovary syndrome and other types of benign disorders contributed to the major increase. CONCLUSIONS: Although the disease burden of gynecological diseases decreased slightly between 1990 and 2019 globally, it remained highest in low SDI countries. The disease burden in 20-24-year age group exhibited the fastest growth, with polycystic ovary syndrome and other types of benign disorders playing a significant role. Urgent and effective measures should be taken to target different age groups, types of gynecological disease and regions with high disease burdens.

How to Keep the Balance between Red and Processed Meat Intake and Physical Activity Regarding Mortality: A Dose-Response Meta-Analysis.

BACKGROUND: Non-communicable diseases have become a major threat to public health, with cardiovascular diseases (CVDs) and cancer being the top two causes of death each year. OBJECTIVE: Our objective is to evaluate the balanced association between the effect of red and processed meat intake on the risk of death and the effect of physical activity on the risk of mortality, where the risk of death includes all causes, CVDs, and cancers. METHODS: We searched electronic databases, including PubMed, ISI Web of Science, Embase, and the Cochrane Library, for prospective studies reporting risk estimates for the association between the intake of red and processed meat, walking, and muscle-strengthening activity (MSA) and the risk of mortality from all causes, CVDs, and cancer. We extracted fully adjusted effect estimates from original studies and performed a summary analysis using the fixed and random-effect models. RESULTS: A conventional meta-analysis showed that red meat and processed meat were positively associated with the risk of mortality, and daily steps and MSA were negatively associated with the risk of death. Further analysis of the dose-response relationship showed that a risk reduction (20%) from 39.5 min/week of MSA or 4100 steps/d was equivalent to an increased risk of all-cause mortality from a daily intake of 103.4 g/d of red meat or 50 g/d of processed meat. The risk was further decreased as the number of steps per day increased, but the risk reversed when the MSA exceeded the threshold (39.5 min/week). CONCLUSIONS: Adherence to physical activity is an effective way to reduce the risk of mortality due to meat intake. However, the total intake of red meat and processed meat should be controlled, especially the latter. Walking is recommended as the main daily physical activity of choice, while MSAs are preferred when time is limited, but it should be noted that longer MSAs do not provide additional benefits.

Development and validation of 18F-FDG PET/CT radiomics-based nomogram to predict visceral pleural invasion in solid lung adenocarcinoma.

OBJECTIVES: This study aimed to establish a radiomics model based on 18F-FDG PET/CT images to predict visceral pleural invasion (VPI) of solid lung adenocarcinoma preoperatively. METHODS: We retrospectively enrolled 165 solid lung adenocarcinoma patients confirmed by histopathology with 18F-FDG PET/CT images. Patients were divided into training and validation at a ratio of 0.7. To find significant VPI predictors, we collected clinicopathological information and metabolic parameters measured from PET/CT images. Three-dimensional (3D) radiomics features were extracted from each PET and CT volume of interest (VOI). Receiver operating characteristic (ROC) curve was performed to determine the performance of the model. Accuracy, sensitivity, specificity and area under curve (AUC) were calculated. Finally, their performance was evaluated by concordance index (C-index) and decision curve analysis (DCA) in training and validation cohorts. RESULTS: 165 patients were divided into training cohort (n = 116) and validation cohort (n = 49). Multivariate analysis showed that histology grade, maximum standardized uptake value (SUVmax), distance from the lesion to the pleura (DLP) and the radiomics features had statistically significant differences between patients with and without VPI (P < 0.05). A nomogram was developed based on the logistic regression method. The accuracy of ROC curve analysis of this model was 75.86% in the training cohort (AUC: 0.867; C-index: 0.867; sensitivity: 0.694; specificity: 0.889) and the accuracy rate in validation cohort was 71.55% (AUC: 0.889; C-index: 0.819; sensitivity: 0.654; specificity: 0.739). CONCLUSIONS: A PET/CT-based radiomics model was developed with SUVmax, histology grade, DLP, and radiomics features. It can be easily used for individualized VPI prediction.

A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality.

The associations between social isolation, loneliness and the risk of mortality from all causes, cardiovascular disease (CVD) and cancer are controversial. We systematically reviewed prospective studies on the association between social isolation, loneliness and mortality outcomes in adults aged 18 years or older, as well as studies on these relationships in individuals with CVD or cancer, and conducted a meta-analysis. The study protocol was registered with PROSPERO (reg. no. CRD42022299959). A total of 90 prospective cohort studies including 2,205,199 individuals were included. Here we show that, in the general population, both social isolation and loneliness were significantly associated with an increased risk of all-cause mortality (pooled effect size for social isolation, 1.32; 95% confidence interval (CI), 1.26 to 1.39; P < 0.001; pooled effect size for loneliness, 1.14; 95% CI, 1.08 to 1.20; P < 0.001) and cancer mortality (pooled effect size for social isolation, 1.24; 95% CI, 1.19 to 1.28; P < 0.001; pooled effect size for loneliness, 1.09; 95% CI, 1.01 to 1.17; P = 0.030). Social isolation also increased the risk of CVD mortality (1.34; 95% CI, 1.25 to 1.44; P < 0.001). There was an increased risk of all-cause mortality in socially isolated individuals with CVD (1.28; 95% CI, 1.10 to 1.48; P = 0.001) or breast cancer (1.51; 95% CI, 1.34 to 1.70; P < 0.001), and individuals with breast cancer had a higher cancer-specific mortality owing to social isolation (1.33; 95% CI, 1.02 to 1.75; P = 0.038). Greater focus on social isolation and loneliness may help improve people's well-being and mortality risk.

Molecular Subtypes Based on Cuproptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Colorectal Cancer.

Recent studies have demonstrated the biological significance of cuproptosis modification, a newly discovered programmed cell death, in tumor progression. Nonetheless, the potential role of cuproptosis-related genes (CRGs) in the immune landscape and tumor microenvironment (TME) formation of colorectal cancer (CRC) remains unknown. We comprehensively assessed cuproptosis modification patterns of 1339 CRC samples based on 27 CRGs and systematically analyzed the correlation of these patterns with TME. The CRG-score was constructed to quantify cuproptosis characteristics by LASSO and multivariate Cox regression methods, and its predictive capability was validated in an independent cohort. We identified three distinct cuproptosis modification patterns in CRC. The TME immune cell infiltration demonstrated immune heterogeneity among these three subtypes. Enrichment for multiple metabolism signatures was pronounced in cluster A. Cluster C was significantly correlated with the signaling pathways of immune activation-related, resulting in poor prognoses. Cluster B with mixed features possibly represents a transition phenotype or intratumoral heterogeneity. Then, based on constructed eight-gene CRG-score, we found that the signature could predict the disease-free survival of CRC patients, and the low CRG-score was related to increased neoantigen load, immunity activation, and microsatellite instability-high (MSI-H). Additionally, we observed significant correlations of the CRG-score with the cancer stem cell index and chemotherapeutic drug susceptibility. This study demonstrated that cuproptosis was correlated with tumor progression, prognosis, and TME. Our findings may improve the understanding of CRGs in TME infiltration characterization of CRC patients and contribute to guiding more effective clinical therapeutic strategies.

Effect of Isomaltulose on Glycemic and Insulinemic Responses: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Evidence regarding the effect of isomaltulose on glycemic and insulinemic responses is still conflicting, which limits isomaltulose's application in glycemic management. The purpose of this study was to comprehensively evaluate its effectiveness and evidence quality. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) prior to October 2021. RCTs were eligible for inclusion if they enrolled adults to oral intake of isomaltulose or other carbohydrates dissolved in water after an overnight fast and compared their 2-h postprandial glucose and insulin concentrations. The DerSimonian-Laird method was used to pool the means of the circulating glucose and insulin concentrations. Both random-effects and fixed-effects models were used to calculate the weighted mean difference in postprandial glucose and insulin concentrations in different groups. Subgroup, sensitivity, and meta-regression analyses were also conducted. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Finally, 11 RCTs (n = 175 participants) were included. The trials were conducted in 4 countries (Japan, Brazil, Germany, and the Netherlands), and all of the enrolled participants were >18 y of age with various health statuses (healthy, type 2 diabetes, impaired glucose tolerance, and hypertension). Moderate evidence suggested that oral isomaltulose caused an attenuated glycemic response compared with sucrose at 30 min. Low evidence suggested that oral isomaltulose caused an attenuated but more prolonged glycemic response than sucrose and an attenuated insulinemic response. Low-to-moderate levels of evidence suggest there may be more benefit of isomaltulose for people with type 2 diabetes, impaired glucose tolerance, or hypertension; older people; overweight or obese people; and Asian people. The study was registered on PROSPERO (International Prospective Register of Systematic Reviews) as CRD42021290396 (available at https://www.crd.york.ac.uk/prospero/).

Are dietary factors involved in the association of CDH4 methylation and breast cancer risk?

DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits can alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell-cell adhesion glycoproteins. We conducted a case-control study (380 newly diagnosed BC and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL DNA), as well as its combined and interactive effects with dietary factors on BC risk. A case-only study (335 newly diagnosed BC) was conducted to analyse the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation was detected using quantitative methylation-specific PCR. Unconditional logistic regressions were used to analyse the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj) = 2·70, (95 % CI 1·90, 3·83), P < 0·001). CDH4 hypermethylation also showed significant combined effects with the consumption of vegetables (ORadj = 4·33, (95 % CI 2·63, 7·10)), allium vegetables (ORadj = 7·00, (95 % CI 4·17, 11·77)), fish (ORadj = 7·92, (95 % CI 3·79, 16·53)), milk (ORadj = 6·30, (95 % CI 3·41, 11·66)), overnight food (ORadj = 4·63, (95 % CI 2·69, 7·99)), pork (ORadj = 5·59, (95 % CI 2·94, 10·62)) and physical activity (ORadj = 4·72, (95 % CI 2·87, 7·76)). Moreover, consuming milk was significantly related with decreased risk of CDH4 methylation (OR = 0·61, (95 % CI 0·38, 0·99)) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.

Global burden of type 2 diabetes in adolescents and young adults, 1990-2019: systematic analysis of the Global Burden of Disease Study 2019.

OBJECTIVE: To estimate the global burden of type 2 diabetes in adolescents and young adults (aged 15-39 years) from 1990 to 2019. DESIGN: Systematic analysis. DATA SOURCE: Global Burden of Disease Study 2019. Participants aged 15-39 years from 204 countries and territories, 1990-2019. MAIN OUTCOMES MEASURES: Age standardised incidence rate, age standardised disability adjusted life years (DALY) rate, and age standardised mortality rate for type 2 diabetes in people aged 15-39 years from 1990 to 2019, and proportional DALY attributable to different risk factors. RESULTS: From 1990 to 2019, significant increases in age standardised incidence rate and age standardised DALY rate were found for type 2 diabetes in adolescents and young adults globally (P<0.001). Age standardised incidence rate (per 100 000 population) increased from 117.22 (95% confidence interval 117.07 to 117.36) in 1990 to 183.36 (183.21 to 183.51) in 2019, and age standardised DALY rate (per 100 000 population) increased from 106.34 (106.20 to 106.48) in 1990 to 149.61 (149.47 to 149.75) in 2019. The age standardised mortality rate (per 100 000 population) was modestly increased from 0.74 (0.72 to 0.75) in 1990 to 0.77 (0.76 to 0.78) in 2019. When grouped by countries with different sociodemographic indexes, countries with a low-middle and middle sociodemographic index had the highest age standardised incidence rate and age standardised DALY rate in 2019, whereas countries with a low sociodemographic index had the lowest age standardised incidence rate but the highest age standardised mortality rate. Women generally had higher mortality and DALY rates than men at ages <30 years, but differences between the sexes were reversed in those aged >30 years except in countries with a low sociodemographic index. The main attributable risk factor for DALY for early onset type 2 diabetes was high body mass index in all regions by sociodemographic index. The proportional contribution of other risk factors varied across regions, however, with higher proportions of ambient particulate air pollution and smoking in countries with a high sociodemographic index and higher proportions of household air pollution from solid fuels and diet low in fruit in countries with a low sociodemographic index. CONCLUSIONS: Early onset type 2 diabetes is a growing global health problem in adolescents and young adults, especially in countries with a low-middle and middle sociodemographic index. A greater disease burden in women aged <30 years was found. Specific measures are needed in countries with different levels of socioeconomic development because of the variable attributable risk factors for type 2 diabetes in adolescents and young adults.

DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden.

Background: Immune checkpoint inhibitor (ICI) therapy has proven to be a promising treatment for colorectal cancer (CRC). We aim to investigate the relationship between DNA methylation and tumor mutation burden (TMB) by integrating genomic and epigenetic profiles to precisely identify clinical benefit populations and to evaluate the effect of ICI therapy. Methods: A total of 536 CRC tissues from the Cancer Genome Atlas (TCGA) with mutation data were collected and subjected to calculate TMB. 80 CRC patients with high TMB and paired normal tissues were selected as training sets and developed the diagnostic and prognostic methylation models, respectively. In the validation set, the diagnostic model was validated in our in-house 47 CRC tissues and 122 CRC tissues from the Gene Expression Omnibus (GEO) datasets, respectively. And a total of 38 CRC tissues with high TMB from the COLONOMICS dataset verified the prognostic model. Results: A positive correlation between differential methylation positions and TMB level was observed in TCGA CRC cohort (r=0.45). The diagnostic score that consisted of methylation levels of four genes (ADHFE1, DOK6, GPR75, and MAP3K14-AS1) showed high diagnostic performance in the discovery (AUC=1.000) and two independent validation (AUC=0.946, AUC=0.857) datasets. Additionally, these four genes showed significant positive correlations with NK cells. The prognostic score containing three genes (POU3F3, SYN2, and TMEM178A) had significantly poorer survival in the high-risk TMB samples than those in the low-risk TMB samples (P=0.016). CRC patients with low-risk scores combined with TMB levels represent a favorable survival. Conclusions: By integrating analyses of methylation and mutation data, it is suggested that DNA methylation patterns combined with TMB serve as a novel potential biomarker for early screening in more high-TMB populations and for evaluating the prognostic effect of CRC patients with ICI therapy.

Integrated multi-omics uncovers reliable potential biomarkers and adverse effects of zinc deficiency.

BACKGROUND: Zinc deficiency is a worldwide public health problem. Currently, there are no established biomarkers available for the accurate diagnosis of zinc-deficiency in individuals. Additionally, a comprehensive view of the adverse effects of zinc deficiency is lacking. Our aim was to identify superior biomarkers of zinc deficiency and uncover the adverse effects of zinc deficiency. METHODS: We performed multi-omics analysis using serum proteomics-metabolomics and liver proteomics on zinc-deficient rats to identify candidate biomarkers and reveal the associated adverse effects of zinc deficiency. Secondly, the candidate biomarkers were validated in two zinc-deficient populations and an RCT zinc supplementation trial on a zinc-deficient population. RESULTS: Our integrated multi-omics approach revealed numerous biomarkers (>2000) and glutathione metabolism as the most important changed pathway in zinc deficiency. Three candidate biomarkers from glutathione metabolism were validated in repeated zinc-deficient rats by quantitative analysis. Only glutathione sulfotransferase omega-1 (GSTO1) (among 3 candidate biomarkers) was validated in the two zinc-deficient populations and zinc-supplemented population. Compared with serum zinc, serum GSTO1 yielded a better response to zinc supplementation and a higher correlation coefficient with zinc intake and the AUC value and has the potential for diagnosing zinc deficiency. By integrated multi-omics, we identified both established and novel adverse effects of zinc deficiency. CONCLUSIONS: Our integrated multi-omics analysis revealed more complete information about zinc deficiency; GSTO1 was found to be a reliable potential biomarker for diagnosis of zinc deficiency. This trial is registered at http://www.chictr.org.cn/registry.aspx as ChiCTR1900028162.

High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer's Disease.

Alzheimer's disease (AD) is an aging-related neurodegenerative disease. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population. To analyze the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Spearman's correlation analysis and random forest were applied to model the relationship between age and each metabolite. Moreover, a systematic review of metabolomics studies of AD in the PubMed, Cochrane and Embase databases were searched to extract the differential metabolites and altered pathways from original studies. Pathway enrichment analysis was conducted using Mummichog. In total, 669 metabolites were significantly altered with aging, and 12 pathways were enriched and correlated with aging. Three pathways (purine metabolism, arginine and proline metabolism, and the TCA cycle) were shared between aging and AD. Arginine and proline metabolism play a key role in the progression from healthy to mild cognitive impairment and to AD in the natural aging population. Three metabolites, 16-a-hydroxypregnenolone, stearic acid and PC[16:0/22:5(4Z,7Z,10Z,13Z,16Z)] were finally proposed as potential markers of AD in the natural aging population. The underlying mechanism shared between aging and AD and the potential biomarkers for AD diagnosis were proposed based on multistep comparative analysis.

Comparisons of different vitamin D supplementation for prevention of osteoporotic fractures: a Bayesian network meta-analysis and meta-regression of randomised controlled trials.

Previous randomised controlled trials have shown the controversial effectiveness of oral vitamin D supplementation in preventing osteoporotic fractures. PubMed, EMBASE and Cochrane Library electronic databases were searched. Pairwise meta-analysis, Bayesian network meta-analysis and meta-regression were applied. A total of 33 studies containing 83,083 participants were included. Oral vitamin D supplementation showed no statistically significant on reducing the risk of total fractures (RR = 0.96, 95%CI = 0.87-1.05 p = 0.389). Vitamin D3 (700-800IU/d) plus calcium showed statistical significance in reducing the incidence of total, hip and non-vertebral fractures in the pairwise meta-analysis. Significant reductions were specifically identified in female in total and hip fractures. However, we did not observe any above significant results using Bayesian network meta-analyses. Strikingly, a meta-regression analysis identified an inverse association between the efficacy of fracture prevention and increased body mass index. Thus, we recommended that the vitamin D dose should be adjusted according to BMI based on further confirmation.

Association between plasma prostaglandin E2 level and colorectal cancer.

Evidences for the personalized use of nonsteroidal anti-inflammatory drugs (NSAIDs) in colorectal cancer (CRC) prevention and treatment that include consideration of prostaglandin E2 levels are necessary. This study was designed as a case-control study including 60 CRC patients and 120 cancer-free controls. A sensitive empirical method, precolumn derivatization HPLC, was used to determine plasma PGE2 levels. The TaqMan SNP Genotyping Assay was used for the genotyping of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms. Multivariate logistic regression analysis suggested that 1 log10(PGE2) increase would result in a 3.64-fold increase in the risk of CRC. Moreover, subjects with log10(PGE2) level in the 75th percentile had a significantly higher risk of CRC than those with log10(PGE2) levels in the 25th percentile [odds ratio (OR), 3.50; 95% confidence interval (CI), 1.35-9.05]. This association was more evident after adjustment for history of NSAIDs use (OR, 3.85; 95% CI, 1.46-10.16). Preliminarily, 260.02 and 414.95 pg/ml might be proposed as the preventive and warning cutoff values of plasma PGE2 for CRC. The preferred NSAIDs dose for patients with the AG+GG (rs689466) and CC+CT (rs5275) genotypes should be higher than that of patients carrying AA or TT genotypes, despite the presence of equal plasma PGE2 levels. We show for the first time that the plasma PGE2 level is associated with the risk of CRC. We provide a preliminary suggestion for NSAIDs doses adjustment according to PTGS2 genotypes after consideration of plasma PGE2 levels.

Differential Metabolic Alterations and Biomarkers Between Gastric Cancer and Colorectal Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Numerous metabolomics studies have been conducted to detect the metabolic mechanisms and biomarkers related to gastric cancer and colorectal cancer. Because of the common metabolic features between gastric cancer and colorectal cancer, a differential diagnosis is difficult. Here, we performed a systematic review and meta-analysis to identify differential metabolic biomarkers between these two types of cancers. MATERIALS AND METHODS: PubMed, Embase, and ScienceDirect were searched to identify all metabolomics studies of gastric cancer and colorectal cancer published up to September 2018. Differential metabolites or altered pathways were extracted. The intersections and differences for these metabolites and pathways between gastric cancer and colorectal cancer were compared. Candidate biomarker sets for diagnosis were proposed from biofluid or feces by comparing them with tumor tissues. RESULTS: Totally, 24 and 65 studies were included in gastric cancer and colorectal cancer, and 223 and 472 differential metabolites were extracted, respectively. Eight pathways were reproducibly enriched in blood, tissue and urine in gastric cancer, while, 11 pathways were reproducibly enriched in blood, urine, feces and tissue in colorectal cancer. Candidate metabolic biomarker sets in blood, urine, or feces for these two cancers were proposed. We found 27 pathways (categorized into eight classifications) common to both cancers, five pathways involving 35 metabolites enriched only in gastric cancer, and eight pathways involving 54 metabolites enriched only in colorectal cancer. CONCLUSION: The altered metabolic pathways showed signatures of abnormal metabolism in gastric cancer and colorectal cancer; the potential metabolic biomarkers proposed in this study have important implications for the prospective validation of gastric cancer and colorectal cancer.

Metabolomic Markers of Colorectal Tumor With Different Clinicopathological Features.

Background: Colorectal cancer (CRC) is the result of complex interactions between the tumor's molecular profile and metabolites produced by its microenvironment. Despite recent studies identifying CRC molecular subtypes, a metabolite classification system is still lacking. We aimed to explore the distinct phenotypes and subtypes of CRC at the metabolite level. Methods: We conducted an untargeted metabolomics analysis of 51 paired tumor tissues and adjacent mucosa using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Multivariate analysis including principal component analysis, orthogonal partial least squares discriminant analysis and heat maps, univariate analysis, and pathway analysis were used to identify potential metabolite phenotypes of CRC. Unsupervised consensus clustering was used to identify robust metabolite subtypes, and evaluated their clinical relevance. Results: A total of 173 metabolites (including nucleotides, carbohydrates, free fatty acids, and choline) were identified between CRC tumor tissue and adjacent mucosa. We found that lipid metabolism was closely related to the occurrence and progression of CRC. In particular, CRC tissues could be divided into three subtypes, and statistically significant correlations between different subtypes and clinical prognosis were observed. Conclusions: CRC tumor tissue exhibits distinct metabolite phenotypes. Metabolite differences between subtypes may provide a basis and direction for further clinical individualized treatment planning.

Multiple exposure to environmental factors and variations in CYP27B1 and the microRNA-binding site of IL-13 are associated with breast cancer risk.

PURPOSE: Several molecular epidemiology studies have evidenced an association of environmental factors and genetic polymorphisms with breast cancer (BC) risk. However, most have considered the functions of a single element rather than combined effects. METHODS: This case-control study of 693 newly-diagnosed BC cases and 714 cancer-free controls evaluated the effect of multiple exposures to environmental factors and polymorphisms in CYP27B1 and IL-13 on BC risk. Genotypes were detected using TaqMan genotyping. Combinations and interactions were analyzed using cross-over analysis and multivariate logistic regression. Combining exposure models were assessed using classification and regression tree and multivariate logistic regression analyses. RESULTS: No significant independent association was observed for any polymorphism in CYP27B1 or IL-13 with the risk of BC. However, significant combined effects were noted for ≥1 time/wk physical activity with rs10877012 (adjusted odds ratio [ORadj ] = 0.21, 95% confidence interval [CI] = 0.11-0.39) and rs4646536 (ORadj  = 0.21, 95% CI = 0.11-0.39) in CYP27B1. Furthermore, taking garlic ≥4 times/wk, ≥1 time/wk physical activity, and a psychological index score ≥33 all displayed significant combined effects with three IL-13 polymorphisms. These relationships remained significant after Bonferroni correction for multiple comparisons. Combining exposure models indicated that compared with consuming garlic ≥4 times/wk, five models (model 5, ORadj  = 2.94, 95% CI = 1.07-8.06; model 6, ORadj  = 10.26, 95% CI = 5.81-18.10; model 7, ORadj  = 5.05, 95% CI = 2.78-9.17; model 8, ORadj  = 3.95, 95% CI = 2.79-5.58; and model 9, ORadj  = 7.97, 95% CI = 5.26-12.07) showed a significant increased risk. CONCLUSIONS: Our findings suggest that personalized adjustments to diet and behavioral patterns may aid BC prevention in variant carriers of CYP27B1 and IL-13.

Dietary factors and polymorphisms in vitamin D metabolism genes: the risk and prognosis of colorectal cancer in northeast China.

CYP24A1 and CYP27B1 are critical genes determining 1α,25(OH)2D3 concentration and impacting on carcinogenesis. A case-control study including 528 colorectal cancer (CRC) patients and 605 cancer-free controls and a follow-up study with 317 cases were conducted in northeast China. Genotypes were tested by TaqMan Genotyping Assays. Individuals carrying the GG genotype of CYP27B1 G > T (rs10877012) exhibited decreased CRC risk compared with those with the TT genotype (ORadjusted (ORadj) = 0.57, 95% Confidence Interval (CI) = 0.38-0.84). Compared with the TT genotype, a significant association between the CC genotype of CYP27B1 C > T (rs4646536) and a reduced risk of CRC was observed (ORadj = 0.59, 95% CI = 0.40-0.88). We also observed significant combined effects of the two polymorphisms in CYP27B1 with dietary factors, including the intake of cereals, overnight meal, allium vegetables, pork, canned fruit, and braised fish, on CRC risk. These associations remained significant after Bonferroni correction for multiple comparisons. The Hazard Ration (HR) of patients with the AA genotype (CYP24A1 A > G, rs4809957) was 2.38 (95% CI = 1.30-4.37) when compared with the GG genotype. Thus, our findings suggested that two polymorphisms in CYP27B1 are associated with CRC susceptibility. CYP24A1 A > G (rs4809957) polymorphism may lead to a worse prognosis of CRC.

Dietary factors and microRNA-binding site polymorphisms in the IL13 gene: risk and prognosis analysis of colorectal cancer.

Long-term dietary intake influences the structure and activity of microorganisms residing in the human gut. The immune response and gut microbiota have a mutual influence on the risk of colorectal cancer (CRC). This study examines the association of gut microbiota-related dietary factors and polymorphisms in the microRNA-binding site of the interleukin 13 gene (IL13) with the risk and prognosis of CRC. Three polymorphisms (rs847, rs848, and rs1295685) were selected for genotyping in a case-control study (513 cases, 572 controls), and 386 CRC patients were followed up. Two dietary factors closely related with gut microbiota (allium vegetables, overnight meal) were significantly associated with CRC development. Although the three SNPs showed no statistically significant associations with the risk and prognosis of CRC, a significant antagonistic interaction was found between rs848 (G-T) and allium vegetable intake (ORi (odds ratio of interaction), 0.92; 95% CI (confidence interval): 0.86, 0.99; P = 0.03); moreover, significant combined and synergistic interactions were observed for all three SNPs and overnight meal intake. This is the first report of significant combined and interactive effects between dietary factors and polymorphisms in the microRNA binding site of IL13 in CRC and may provide direct guidance on intake of allium vegetable and overnight meals for individuals with specific genetic variants of IL13 to modify their susceptibility to CRC.