No abstract

Dear Editor, Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. 1 Shifting the detection of CRC to earlier stages via massive screening has considerably reduced mortality. 2 Metabolomics has shown great potential in the identification of noninvasive biomarkers of CRC. However, the huge number and inconsistent reports of putative markers make choosing the most appropriate biomarkers difficult. The aim of this study was to identify the metabolic markers of CRC by a multi-step strategy. We first identified and verified differential plasma metabolites of CRC by a two-stage case-control design. The tumour specificity of plasma markers was then confirmed by comparison with tumor-adjacent non-malignant paired tissue. Moreover, we conducted a systematic review of metabolomics studies of CRC to affirm the markers in multiple populations. Finally, the metabolites were quantitatively evaluated in an independent case-control population (Figure 1).A two-stage case-control study involving 170 cases and 197 controls was performed. All patients were diagnosed at the Third Affiliated Hospital of Harbin Medical University. Controls were recruited from patients in the orthopaedic and ophthalmology departments and volunteers from Xiangfang District of Harbin City during the same period. Fasting peripheral venous blood was obtained in the morning in the hospital or medical examination centre. Metabolic profiling analysis was conducted on a ultra performance liquid chromatography (UPLC)/ Q-time-of-flight (TOF)-mass spectrometry (MS)/MS platform. Principal component analysis and orthogonal projections to latent structures discriminant analysis were performed to check the separation tendency. Student's t-test or Wilcoxon's rank-sum test with an adjusted P-value was applied to test the metabolites between cases and controls (details in Supporting Information, Section 1.1).No significant differences in age, sex or body mass index were observed between the cases and controls in This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background: DNA methylation, which has been demonstrated to be influenced by dietary factors, is associated with changes in breast cancer (BC) risk and clinicopathological features.Methods: A case-control study (271 newly diagnosed cases, 326 controls) was conducted to evaluate the effect of dietary factors and HS3ST2 methylation in peripheral blood leukocyte DNA on the risk of BC. Moreover, a case-only study (298 cases) was designed to evaluate the effects of dietary factors on HS3ST2 methylation in tumor tissue and the relationship of methylation with clinicopathological features.Results: The dietary consumption of fruit, poultry, marine fish, milk, and pork and regular exercise was significantly associated with changes in the risk of BC. We also found a significant association between HS3ST2 hypermethylation and BC risk (odds ratio [OR] = 1.618, 95% confidence interval [CI] = 1.077–2.243). The combined effects of HS3ST2 hypermethylation and lower fruit intake (<500 vs. ≥500 g/week, OR = 2.553, 95% CI = 1.328–4.908), poultry (<1 vs. ≥1/week, OR = 3.197, 95% CI = 1.598– 6.385), marine fish (<1 vs. ≥1 time/month, OR = 4.272, 95% CI = 2.117–8.621), and milk (<3 vs. ≥3 times/week, OR = 6.072, 95% CI = 2.399–15.568) and irregular exercise (<1 vs. ≥1 time/week, OR = 4.149, 95% CI = 1.908–9.022) were significantly associated with an increased risk of BC. The consumption of canned meat was associated with the hypermethylation status of HS3ST2 in BC tissues (OR = 3.884, 95% CI = 1.078–13.991). HS3ST2 hypermethylation was significantly associated a basal-like status (vs. luminal A, OR = 1.981, 95% CI = 1.036–3.787) and estrogen receptor negativity (Negative vs. Positive, OR = 1.744, 95%CI = 1.053-2.887) in BC tissues and TNM stages II–IV (II–IV vs. I, OR = 1.692, 95% CI = 1.040–2.752) in peripheral blood leukocyte DNA. Conclusion: Maintaining healthy dietary habits is of great significance for preventing BC, especially for women with HS3ST2 hypermethylation.

Background We aimed to assess the associations between social isolation (SI) and the risk of mortality from all causes, cardiovascular disease, and cancer. Methods This was a systematic review and meta-analysis of prospective cohort studies.We searched electronic databases, including PubMed, Web of Science, and Embase, from inception until October 2021, as well as the references of retrieved articles. Prospective studies reporting risk estimates for the association between SI and mortality from all causes, cardiovascular diseases, and cancer in adults aged 18 or older were included in the analyses. Data were screened and extracted independently by two investigators. The fully adjusted effect sizes in the original studies were analyzed, and summary analyses were performed using a fixed-effects or random-effects model, according to the heterogeneity among studies. Subgroup analyses, meta-regression, and sensitivity analyses were performed to evaluate the heterogeneity and robustness of the findings. Simple linear regression was used to analyze the changing trends in social network index grade and risk of mortality. The risk of publication bias was tested using funnel plots and Egger’s and Begg’s tests (each significant at P < 0.05). The trim-and-fill method was used to adjust for the influence of potentially unpublished studies on pooled effect estimates when statistical tests indicated publication bias. The study protocol was registered with PROSPERO (reg. NO CRD42022299959) Results A total of 50 prospective cohort studies with 1,951,661 individuals were included for analysis. The duration of follow-up among included studies ranged from 6 months to 24.4 years. In pooled analyses, SI was significantly associated with an increased risk of mortality from all causes (pooled effect size, 1.22; 95% confidence interval [CI], 1.16 to 1.29; I2 = 77.6%), cardiovascular disease (1.35; 95% CI 1.25 to 1.45, I2 = 65.5%), and cancer (1.23; 95% CI 1.18 to 1.27, I2 = 44.2%) in the general population. Linear regression showed that social network index grade was significantly correlated with the risk of all-cause mortality (P < 0.001). Additionally, the pooled effect estimate for all-cause mortality in patients with breast cancer was 1.51 (95% CI 1.34 to 1.70), and that for cancer-specific mortality was 1.33 (95% CI 1.02 to 1.75). There was a 28% increased risk of all-cause mortality in socially isolated patients with cardiovascular disease (95% CI 1.10 to 1.48). There was no evidence of a positive association between SI and cancer-specific mortality in patients with colorectal cancer (1.07, 95% CI 0.96 to 1.20). Conclusions SI was associated with at least a 20% increased risk of all-cause mortality, cardiovascular disease mortality, and cancer mortality. We highlight that social isolation contributes to chronic disease and mortality, with efforts to improve social isolation likely to have benefits in well-being and survival.