Risk Of Digestive System Cancers Research Articles

Oral dysbiosis and risk of gastrointestinal cancers: A systematic review and meta-analysis of longitudinal studies.

Poor oral health and oral dysbiosis were found to be associated with cancers, especially of the gastrointestinal (GI)system. But the cause-and-effect relationship and the effect of the risk are not yet known due to scarcity of literature. Understanding such risk relationship can contribute to an integrated multi-disciplinary approach for GI cancer prevention. The aim of the present systematic review and meta-analysis is to assess the role of oral dysbiosis on increasing the risk of digestive system cancers. To evaluate the effect of poor oral health on increasing the risk of gastrointestinal cancers. We conducted a systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in databases PubMed, Elsevier, Wiley's online library and Web of Science from inception to February 2023 to include recent cohort studies that assessed the association between poor oral health and the risk of cancer. We assessed bias using the New Castle Ottawa scale. We used inferential statistics to describe the effect of oral dysbiosis on gastrointestinal cancers. We performed a sub-group analysis to assess the effect of oral conditions on individual cancers. We included 10 longitudinal studies in the meta-analysis. The overall effect size of poor oral health and GI cancer risk was hazard's ratio (HR) =1.30 (95% CI: [1.14, 1.46]) (p<0.001) (I2 = 68.78). Sub-group analysis indicated that poor oral health increases the risk of esophageal cancer HR=1.61 (95% CI: [1.37, 1.85]), stomach cancer HR=1.33 (95% CI: [1.08, 1.58]), pancreatic cancer HR=1.90 (95%CI; [1.29, 2.50]) and colorectal and hepatocellular carcinoma HR=1.16 (95% CI: [1.08, 1.23]). The meta-analysis indicated that poor oral health was significantly associated with increasing the risk of GI cancers.

Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses

BackgroundThe roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk.MethodsHDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses.ResultsA median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (Pnonlinearity < 0.05, Poverall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (Pnonlinearity > 0.05, Poverall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (Pnonlinearity > 0.05, Poverall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047).ConclusionsOur findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.

Early life exposure to Chinese famine and risk of digestive system cancer in midlife.

To investigate whether early-life exposure to the Great Famine of 1959-1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4±2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer.

Association between green tea intake and digestive system cancer risk in European and East Asian populations: a Mendelian randomization study.

Previous observational studies have shown that green tea consumption is associated with a reduced incidence of digestive system cancers (DSCs). However, the observed association could be due to confounding factors. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the causal effect of green tea intake on the risk of five common DSCs. Independent genetic variants strongly associated with green tea consumption in European and East Asian populations were selected as instrumental variables in genome-wide association studies involving up to 64,949 European individuals and 152,653 East Asian individuals, respectively. The associations between genetic variants and DSCs were extracted from the FinnGen study and the Japan Biobank. The primary analysis was performed using random-effects inverse variance weighting (IVW). Other MR analyses, including weighted mode-based estimate, weighted-median, MR-Egger regression, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO) analysis, were used for sensitivity analyses. In addition, a multivariate MR design was performed to adjust for smoking and alcohol consumption. The IVW results showed no causal relationship between tea intake and DSCs risk in European population (esophagus cancer: odds ratio (OR) = 1.044, 95% confidence interval (CI) 0.992-1.099, p = 0.096; stomach cancer: OR = 0.988, 95% CI 0.963-1.014, p = 0.368; colorectal cancer: OR = 1.003, 95% CI 0.992-1.015, p = 0.588; liver cancer: OR = 0.996, 95% CI 0.960-1.032, p = 0.808; pancreatic cancer: OR = 0.990, 95% CI 0.965-1.015, p = 0.432). The MR-Egger regression, MR-PRESSO analysis and other methods also confirmed the reliability of the conclusion. Similarly, no significant association was found between green tea consumption and the incidence of DSCs among East Asians. This relationship is not significant even after adjusting for smoking and alcohol consumption (P > 0.05). Our study provides evidence that genetically predicted green tea intake is not causally associated with the development of DSCs in the European and East Asian population.

The Mediating Effect of the Choline-to-Betaine Ratio on the Association Between PEMT rs7946 and Digestive System Cancer: A Nested Case–Control Study in a Chinese Population

BackgroundThe enzyme phosphatidylethanolamine N-methyltransferase (PEMT) is responsible for synthesizing phosphatidylcholine by methylating phosphatidylethanolamine. We hypothesized that a polymorphism of the PEMT gene, rs7946, is involved in carcinogenesis. ObjectivesWe aimed to investigate the relationship between PEMT rs7946 and digestive system cancer and examine possible effect modifiers and mediators. MethodsWe conducted a nested, case–control study within the China H-type Hypertension Registry Study, including 751 cases and 1:1 matched controls. To assess the association of PEMT rs7946 and digestive system cancer, we estimated odds ratios with 95% confidence intervals (CIs) using conditional logistic regression. We used the bootstrap test to examine the potential mediating effects of related metabolites. ResultsOur results revealed that wild-type homozygous CC genotype carriers of PEMT rs7946 had a significantly increased risk [odds ratio (OR): 1.31; 95% CI: 1.04, 1.66; P = 0.023] compared with the TT/CT combined genotypes. The effect was found to be more pronounced in individuals with a lower choline-to-betaine ratio (<0.412, P-interaction = 0.021). Furthermore, the mediation analysis indicated that the choline-to-betaine ratio played a significant role in mediating 13.55% of the association between PEMT rs7946 and digestive system cancer (P = 0.018). ConclusionsOur study suggested that PEMT rs7946 may affect risk of digestive system cancer through direct and indirect pathways, and the choline-to-betaine ratio may partially mediate the indirect effect.This trial was registered at Chinese Clinical Trial Registry as ChiCTR1800017274.

Controlling Risk Factors Reduces Cancer Risk in Patients with Atherosclerotic Cardiovascular Disease: A Cohort Study

BackgroundThe association of atherosclerotic cardiovascular disease (ASCVD) with cancer occurrence is not well examined, and the impact of common risk factors on the risk of cancer in ASCVD patients is not known. This study aimed to explore the effect and possible causes of ASCVD on cancer risk through a cohort study. MethodsA total of 14,665 age- and sex-matched pairs of participants were recruited from the Kailuan cohort (ASCVD vs non-ASCVD). A competing risk model was used to calculate the risk of cancer after ASCVD. ResultsA total of 1124 cancers occurred after 5.80 (3.05-9.44) years of follow-up. The ASCVD group had a reduced risk of cancer (hazard ratio 0.74; 95% confidence interval, 0.65-0.85). Also, the risk of cancer in the digestive system, respiratory system, urinary system, and reproductive system was reduced by 17%, 16%, 14%, and 52%, respectively. According to the status of systolic and diastolic blood pressure, fasting blood glucose, high-sensitivity C-reactive protein and body mass index after ASCVD, the risk of overall cancer and digestive system cancer decreased with the increase in the number of ideal indicators (P for trend < .01). With the increase of follow-up time, the risk of cancer and the 5 site-specific cancers gradually decreased. ConclusionsCancer risk can be reduced by controlling for common risk factors after ASCVD event. This risk reduction is site-specific-, time-, and the number of ideal indicator-dependent.

The association of serum choline concentrations with the risk of cancers: a community-based nested case–control study

Few studies have been designed to investigate the effect of serum choline on the risk of incident cancer. This study aims to explore the association between serum choline and the risk of new-onset cancer. We conducted a case–control study, including 199 patients with incident cancer and 199 matched controls during a median of 3.9 years of follow-up, nested within the China Stroke Primary Prevention Trial. Cubic spline regression (RCS) and conditional logistic regression analysis was used to assess the association of serum choline and incident cancer risk. We observed a positive dose–response association between serum choline levels and the risk of overall (p for overall = 0.046) and digestive system cancer (p for overall = 0.039). Compared with patients with the lowest choline levels (Q1 group), patients in the highest levels of choline (Q4) had a 3.69-fold and 6.01-fold increased risk of overall (OR = 3.69, 95% CI 1.17–11.63) and digestive system cancer (OR = 6.01, 95% CI 1.14–31.67). Elevated choline levels (per SD, 11.49 μg/mL) were associated with a higher risk of overall cancer among participants who were older, male, and smokers in the subgroup analyses. We found a positive association between elevated levels of serum choline with increased risk of incident cancer. Our findings have critical clinical implications for cancer prevention and diagnosis.Trial registration CSPPT, NCT00794885. Registered: November 20, 2008. https://www.clinicaltrials.gov/ct2/show/study/NCT00794885https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.

Association of plasma iron with the risk of incident cancer in Chinese adults with hypertension: a nested case-control study.

Iron is an essential element for organismal health but excessive iron is potentially toxic. However, few observational studies link plasma iron (PI) concentrations and cancer risk, and the results are inconsistent. This study aimed to explore the associations of PI concentrations with cancer risk in Chinese adults with hypertension. We conducted a nested, case-control study, including 223 pairs of incident cancer cases and matched controls from the China Stroke Primary Prevention Trial. The median time between blood sample collection and subsequent cancer event occurrence was 2.13 years. The odds ratio (OR) and 95% confidence interval (CI) for the risk of cancer by PI were estimated from multivariable conditional logistic regression models. There was a nonlinear association between PI concentrations and total cancer risk. When compared with participants in tertile 2 of PI, the ORs of total cancer were 2.17 (95%CI: 1.25-3.85) and 1.29 (95%CI: 0.77-2.19) in participants in PI tertiles 3 and 1, respectively. Furthermore, higher PI was associated with increased digestive system cancer risk (OR=3.25, 95%CI:1.29-8.90), while lower PI was associated with increased risk of non-digestive system cancer (OR=3.32, 95%CI: 1.39-8.71). In a sensitivity analysis, the increases in total cancer risk or digestive system cancer risk were still observed with higher PI after excluding cancer cases occurring within the first year. Our results showed an increased risk of cancer related to higher PI or lower PI in Chinese adults with hypertension. Higher iron levels were linked to an increased risk of digestive system cancers, whereas lower iron levels were linked to an increased risk of non-digestive system cancers.

Selenium intake and multiple health-related outcomes: an umbrella review of meta-analyses.

Selenium is an essential trace metalloid element that is associated with fundamental importance to human health. Our umbrella review aimed to evaluate the quality of evidence, validity, and biases in the relationship between selenium intake and health-related outcomes according to published systematic reviews with pooled data and meta-analyses. Selenium intake is associated with a decreased risk of digestive system cancers, all-cause mortality, depression, and Keshan disease, when in children reduce the risk of Kashin-Beck disease. Additionally, selenium supplementation can improve sperm quality, polycystic ovary syndrome, autoimmune thyroid disease, cardiovascular disease, and infective outcomes. Selenium supplementation also has relationship with a decreased concentration of serum lipids including total cholesterol and very low-density lipoprotein cholesterol. However, no evidence has shown that selenium is associated with better outcomes among patients in intensive care units. Furthermore, selenium intake may be related with a higher risk of type 2 diabetes and non-melanoma skin cancers. Moreover, most of included studies are evaluated as low quality according to our evidence assessment. Based on our study findings and the limited advantages of selenium intake, it is not recommended to receive extra supplementary selenium for general populations, and selenium supplementation should not be continued in patients whose selenium-deficient status has been corrected.

Reduced Sodium in White Brined Cheese Production: Artificial Neural Network Modeling for the Prediction of Specific Properties of Brine and Cheese during Storage

Background: White brined cheese is one of the most frequently consumed cheeses that is accepted among a large group of consumers, which is largely related to its unique sensory properties, which are characterized by specific technological processes including ripening in the brine. Thus, white brined cheese contains a high amount of NaCl, and frequent consumption might lead to excessive sodium intake, which nowadays, presents a global problem. Consequently, food industries have developed reduced sodium products by substitutional salts. Furthermore, various studies have indicated that increased sodium intake via the diet can be associated with cardiovascular diseases, a risk of digestive system cancer, obesity, and other conditions. Calcium salts (citrate and lactate) are safe for human health and can be added to various foods according to the quantum satis rule. The present study aimed to partially replace NaCl with Ca-citrate and Ca-lactate in proportions of 25% and 50%. Additionally, the study presents the possibility of applying Artificial Neural Network (ANN) models for the prediction of some brine and cheese properties. Methods: White brined cheese with substitutional salts in brine (25% and 50% Ca-citrate and 25% and 50% Ca-lactate) were produced and compared to the control cheese ripened in conventionally applied NaCl brine. The acidity, total dissolved solids, salt amount, conductivity, color, and textural and sensory properties were determined over the 28 days of cold storage. Results: The substitution of NaCl with Ca-citrate and Ca-lactate is promising for sodium reduction in white brined cheese, whereby the physical and chemical properties remain acceptable. The best sensory score gain occurred with a substitution of 25% NaCl with Ca-citrate. Furthermore, ANN models can be employed to predict brine and cheese properties during storage.

The association of vitamin D and digestive system cancers: a comprehensive Mendelian randomization study.

Hitherto, the association of vitamin D intake and digestive system cancers occurrence still causes disputation among the researchers. This study aimed to investigate the genetic relation between vitamin D ingestion and digestive system cancers (which are esophageal, gastric, hepatic, pancreatic, and colorectal cancers) by a two-sample Mendelian randomization (MR) analysis, using datasets derived from IEU OpenGWAS database. This study is based on a genome-wide association study (GWAS) for vitamin D and digestive system cancers, with a sample amount ranging from 218,792 to 496,946 European ancestry individuals. The study first investigated the causal relationship between vitamin D and each digestive system cancers using inverse-variance weighting (IVW), weighted medians, and MR-Egger regression and then used meta-analysis to summarize the IVW results for the different cancers. We also performed additional sensitivity tests to assess the validity of the results. In this study, we screened out 117 SNPs as potential instrumental variables for 25(OH)D and identified 101 fixed SNPs as instrumental variables for digestive system cancers. The results of the IVW failed to reveal any causal relationship between the genetically predisposed vitamin D level and the risk of digestive system cancers (esophageal cancer p = 0.400, OR = 1.397, 95% CI 0.642-3.040; gastric cancer p = 0.796, OR = 0.939, 95% CI 0.585-1.510; hepatic cancer p = 0.347, OR = 1.445, 95% CI 0.671-3.109; pancreatic cancer p = 0.905, OR = 0.969, 95% CI 0.581-1.618; colorectal cancer p = 0.127, OR = 0.0.841, 95% CI 0.673-1.051). The pooled ORs (odds ratio) are 0.918 (95% CI 0.770-1.097, p = 0.348). There is no causal relationship between vitamin D and the occurrence of digestive system cancers. The risk of digestive system cancers cannot be alleviated by merely increasing vitamin D intake.

Plant-based dietary patterns and the risk of digestive system cancers in 3 large prospective cohort studies.

Little is known about the relation between plant-based dietary patterns and digestive system cancers. This study investigated the prospective association between 3 pre-defined indices of plant-based dietary pattern and risk of digestive system cancers, as a whole or individually. We utilized data from 3 prospective cohorts, the Nurses' Health Study (1984-2018, 74,496 women aged 65 ± 10.9years), Nurses' Health Study II (1991-2017, 91,705 women aged 49.3 ± 8.3years), and Health Professionals Follow up Study (1986-2016, 45,472 men aged 65.4 ± 11.0years). We used Cox proportional hazards regression models to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) of digestive system cancers across 3 plant-based diet index scores: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). During a follow-up of 4,914,985 person-years, we identified 6,518 cases of digestive system cancers. In the pooled analysis of 3 cohorts, the HRs (95% CIs) per 10-point increase in hPDI score were 0.93 (0.89, 0.97) for total digestive system cancer, 0.94 (0.89, 0.99) for gastrointestinal tract cancer, 0.89 (0.81, 0.98) for accessory organ cancer, and 0.68 (0.52, 0.91) for liver cancer. In contrast, the HRs (95% CIs) per 10-point increase in uPDI score was 1.06 (1.01, 1.11) for gastrointestinal tract cancer and 1.07 (1.01, 1.13) for colorectal cancer. A healthy plant-based dietary pattern was associated with reduced risks of total digestive system cancers as well as individual cancers in thegastrointestinal tract and theaccessory organs. Emphasizing the healthiness and quality of plant-based diets may be important for the prevention of developing cancers in the digestive system.

The association of serum serine levels with the risk of incident cancer: results from a nested case-control study.

Background: Cancer is associated with the dysregulation of serum serine levels, and tumor growth is supported by increased serine biosynthesis. This study aims to explore the association of serum serine levels with incident cancer risk in Chinese hypertensive adults. Materials and methods: 1391 patients with incident cancer and 1391 matched controls in terms of age, sex, and residence with cases in a 1 : 1 ratio were included in this nested case-control study. The serum serine concentrations were determined by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS) at the baseline. The associations of serum serine levels with the risk of overall, digestive system, non-digestive system, and lung cancers (the most common type) were assessed by conditional logistic regression. Results: When serum serine concentration was assessed as quartiles, a significantly higher risk of total cancer (OR = 1.32; 95% CI: 1.01-1.71; P = 0.038) was found in participants in the highest quartile (≥17.68 μg mL-1) compared with participants in the lowest quartile (<13.27 μg mL-1). Similar results were also observed for non-digestive system and lung cancers, but not for digestive system cancers. Significant associations of serum with overall cancer risk were found among all age subgroups, men, non-smokers, non-drinkers, and individuals with lower folic acid levels. Conclusion: High serum serine concentrations were associated with an increased risk of overall, non-digestive system, and lung cancers among Chinese hypertensive adult patients.

The Association of Serum L-Carnitine Concentrations with the Risk of Cancer in Chinese Adults with Hypertension

The effect of serum L-carnitine (LC) concentrations on cancer risk remains unclear. This study aims to explore the association between serum LC and the risk of incident cancer. This is a case-control study, including 574 patients with incident cancer and 574 controls matched in a 1:1 ratio by age, sex, and residence, nested within the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analysis was used to assess the association of serum LC and incident cancer risk. When LC was assessed as quartiles, compared with patients with low LC (Q1), patients in the highest quartile (Q4) had a 33% (OR = 0.67, 95% CI: 0.46 to 0.99), 52% (OR = 0.48, 95% CI: 0.23 to 0.99), and 39% (OR = 0.61, 95% CI: 0.38 to 0.99) decreased risk of overall, digestive system, and non-digestive system cancer in the adjusted models, respectively. In subgroup analyses, an inverse association of LC with cancer risk was observed in individuals who were overweight (obese), who never drink, who never smoke, and who were female. In the mediation analysis, serum trimethylamine-N-oxide (TMAO) concentrations did not mediate the reversed association of LC with cancer risk. This study showed that serum LC concentrations had a protective impact on overall, digestive system, and non-digestive system cancer risk.

Association between serum arginine levels and cancer risk: A community-based nested case-control study.

The effect of arginine on tumors appears to be bidirectional. The association of serum arginine with the risk of incident cancer remains uncovered at present. We aimed to investigate the prospective relationship of baseline serum arginine concentrations with the risk of incident cancer in hypertensive participants. A nested, case-control study with 1,389 incident cancer cases and 1,389 matched controls was conducted using data from the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analyses were performed to evaluate the association between serum arginine and the risk of the overall, digestive system, non-digestive system, and site-specific cancer. Compared with matched controls, cancer patients had higher levels of arginine (21.41 μg/mL vs. 20.88 μg/mL, p < 0.05). When serum arginine concentrations were assessed as quartiles, compared with participants in the lowest arginine quartile, participants in the highest arginine quartile had a 32% (OR = 1.32, 95% CI: 1.03 to 1.71), and 68% (OR = 1.68, 95% CI: 1.09 to 2.59) increased risk of overall and digestive system cancer, respectively, in the adjusted models. In the site-specific analysis, each standard deviation (SD) increment of serum arginine was independently and positively associated with the risk of colorectal cancer (OR = 1.35, 95% CI: 1.01 to 1.82) in the adjusted analysis. We found that hypertensive individuals with higher serum arginine levels exhibited a higher risk of overall, digestive system, and colorectal cancer.

Coffee consumption and cancer risk: a Mendelian randomisation study

BackgroundCoffee contains many bioactive chemicals and associations with cancer have been reported in observational studies. In this Mendelian randomisation (MR) study we investigated the causal associations of coffee consumption with a broad range of cancers. Materials and methodsTwelve independent genetic variants proxied coffee consumption. Genetically-predicted risk of any cancer (59,647 cases) and 22 site-specific cancers was estimated in European-descent individuals in UK Biobank. Univariable and multivariable MR analyses were conducted. ResultsGenetically-predicted coffee consumption was not associated with risk of any cancer in the main analysis (OR 1.05, 95% CI 0.98–1.14, p = 0.183) but was associated with an increased risk of digestive system cancer (OR 1.28, 95% CI 1.09–1.51, p = 0.003), driven by a strong association with oesophageal cancer (OR 2.79, 95% CI 1.73–4.50, p = 2.5×10−5). This association was consistent after adjustment for genetically-predicted body mass index, smoking and alcohol consumption. There was no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied. However, genetically-predicted coffee consumption was associated with increased risk of multiple myeloma (OR 2.25, 95% CI 1.30–3.89, p = 0.004) and reduced ovarian cancer risk (OR 0.63, 95% CI 0.43–0.93, p = 0.020). ConclusionsThis MR study provides strong support for a causal association of coffee consumption with oesophageal cancer, but not for the majority of cancer types, and the underlying mechanisms require investigation.

Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study.

Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, β-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank—the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608–0.985, p = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623–0.936, p = 0.010). Likewise, higher absolute retinol levels suggestively reduced the pancreatic cancer risk in FinnGen—the OR per 10% unit increase in ln-transformed retinol was 0.705 (95% CI 0.529–0.940, p = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584–0.955, p = 0.020). Sensitivity analyses verified the above suggestive evidence. Our findings suggest that higher levels of antioxidants are unlikely to be a causal protective factor for most digestive system cancers, except for the suggestive protective effects of ascorbate on colon cancer and of retinol on pancreatic cancer.

The Relationship Between Plant-Based Diet and Risk of Digestive System Cancers: A Meta-Analysis Based on 3,059,009 Subjects.

Background and ObjectivesDiets containing red or processed meat are associated with a growing risk of digestive system cancers. Whether a plant-based diet is protective against cancer needs a high level of statistical evidence.MethodsWe performed a meta-analysis of five English databases, including PubMed, Medline, Embase, Web of Science databases, and Scopus, on October 24, 2021 to identify published papers. Cohort studies or case-control studies that reported a relationship between plant-based diets and cancers of the digestive system were included. Summary effect-size estimates are expressed as Risk ratios (RRs) or Odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. The inconsistency index (I2) and τ2 (Tau2) index were used to quantify the magnitude of heterogeneity derived from the random-effects Mantel-Haenszel model.ResultsThe same results were found in cohort (adjusted RR = 0.82, 95% CI: 0.78–0.86, P < 0.001, I2 = 46.4%, Tau2 = 0.017) and case-control (adjusted OR = 0.70, 95% CI: 0.64–0.77, P < 0.001, I2 = 83.8%, Tau2 = 0.160) studies. The overall analysis concluded that plant-based diets played a protective role in the risk of digestive system neoplasms. Subgroup analyses demonstrated that the plant-based diets reduced the risk of cancers, especially pancreatic (adjusted RR = 0.71, 95% CI: 0.59–0.86, P < 0.001, I2 = 55.1%, Tau2 = 0.028), colorectal (adjusted RR = 0.76, 95% CI: 0.69–0.83, P < 0.001, I2 = 53.4%, Tau2 = 0.023), rectal (adjusted RR = 0.84, 95% CI: 0.78–0.91, P < 0.001, I2 = 1.6%, Tau2 = 0.005) and colon (adjusted RR = 0.88, 95% CI: 0.82–0.95, P < 0.001, I2 = 0.0%, Tau2 = 0.000) cancers, in cohort studies. The correlation between vegan and other plant-based diets was compared using Z-tests, and the results showed no difference.ConclusionsPlant-based diets were protective against cancers of the digestive system, with no significant differences between different types of cancer.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322276, Identifier: CRD42022322276.

Circulating Clusterin Levels and Cancer Risk: A Systematic Review and Meta-Analysis.

IntroductionThe previous reports on clusterin (CLU) levels in various types of cancer have been controversial and heterogeneous. The present meta-analysis has aimed to evaluate the association between soluble CLU levels and the risk of different human cancers based on observational studies.MethodsA systematic literature review was conducted to determine the relevant eligible studies in English language from health-related electronic databases up to January 2021. Random effects models were used to calculate the summary standard mean difference (SMD) with 95% confidence intervals (CIs) to identify the correlation between CLU levels and cancer risk. The meta-regression, sensitivity, Galbraith, and subgroup analyses were performed to explore the source of between-study heterogeneity. Furthermore, the funnel plot and Egger’s linear regression tests were carried out to evaluate the risk of publication bias.ResultsAccording to 16 eligible articles, 3331 patients and 839 healthy controls were included in our meta-analysis. Overall, the CLU levels were significantly higher in various cancer cases compared to the healthy groups (SMD = 1.50, 95% CI = 0.47–2.53). Moreover, subgroup analysis based on types of cancer showed a significant correlation between CLU levels and the risk of digestive system cancers (SMD = 1.54, 95% CI = 0.91–2.18, P <0.001), especially in HCC (SMD = 1.89, 95% CI = 0.76–3.03, P = 0.001), and CRC (SMD = 1.63, 95% CI = 0.0–3.23, P = 0.048).ConclusionThe present meta-analysis indicates a significant association of CLU levels with the risk of digestive system cancers such as hepatocellular carcinoma and colorectal cancer. Therefore, CLU can be monitored as a novel molecular biomarker for the prognosis and diagnosis of various types of cancers particularly in the digestive system.

Gluten Intake and Risk of Digestive System Cancers in 3 Large Prospective Cohort Studies

Background & AimsIn patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease. MethodsWe leveraged longitudinal data from 3 prospective cohorts, the Nurses’ Health Study (1984–2018, 73,166 women aged 65.1 ± 10.8 years), Nurses’ Health Study II (1991–2017, 90,423 women aged 49.1 ± 8.2 years), and Health Professionals Follow-Up Study (1986–2016, 42,617 men aged 64.8 ± 10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios and 95% confidence intervals of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires. ResultsDuring 4,801,513 person-years of follow-up, we documented 6231 incident digestive system cancer cases among 3 cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a hazard ratio of 0.94 (95% confidence interval, 0.87–1.02) comparing the highest with the lowest quintile of gluten intake (P trend = .05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer. ConclusionsGluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population.