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Taken together, we demonstrated three two-locus pairs of polymorphisms with synergistic effect out of three genes in RAAS and found significant haplotype-phenotype interaction. Functional studies to confirm or refute these findings are warranted.

Evidence is mounting to indicate that cancer patients may have more likelihood of having coronavirus disease 2019 (COVID-19) but lack consistency. A robust estimate is urgently needed to convey appropriate information to the society and the public, in the time of ongoing COVID-19 pandemic. We performed a systematic review and meta-analysis through a comprehensive literature search in major databases in English and Chinese, and two investigators conducted publication selection and data extraction independently. A meta-analysis was used to obtain estimates of pooled prevalence of cancer in patients with COVID-19 and determine the association of cancer with severe events, after assessment of potential heterogeneity, publication bias, and correction for the estimates when necessary. Total 38 studies comprising

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Metabolic syndrome (MetS) has been shown to be associated with an increased risk of gastric cancer. However, the impact of MetS on gastric cancer mortality remains largely unknown. Here, we prospectively examined the prediction of preoperative MetS for gastric cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. This study was conducted among 3012 patients with gastric cancer who received radical gastrectomy between 2000 and 2010. The latest follow-up was completed in 2015. Blood/tissue specimens, demographic and clinicopathologic characteristics were collected at baseline. During 15-year follow-up, 1331 of 3012 patients died of gastric cancer. The median survival time (MST) of patients with MetS was 31.3 months, which was significantly shorter than that of MetS-free patients (157.1 months). The coexistence of MetS before surgery was associated with a 2.3-fold increased risk for gastric cancer mortality (P < 0.001). The multivariate-adjusted hazard ratios (HRs) were increased with invasion depth T1/T2 (HR = 2.78, P < 0.001), regional lymph node metastasis N0 (HR = 2.65, P < 0.001), positive distant metastasis (HR = 2.53, P < 0.001), TNM stage I/II (HR = 3.00, P < 0.001), intestinal type (HR = 2.96, P < 0.001), negative tumor embolus (HR = 2.34, P < 0.001), and tumor size ≤ 4.5 cm (HR = 2.49, P < 0.001). Further survival tree analysis confirmed the top splitting role of TNM stage, followed by MetS or hyperglycemia with remarkable discrimination ability. In this large cohort study, preoperative MetS, especially hyperglycemia, was predictive of significant gastric cancer mortality in patients with radical gastrectomy, especially for early stage of gastric cancer.

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This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow-up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98-fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40-3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor-node-metastasis stage I/II (HR = 3.94, 95% CI: 2.65-5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54-11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85-5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53-4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II.

BackgroundNumerous individually underpowered association studies have been conducted on endothelial nitric oxide synthase (eNOS) genetic variants across different ethnic populations, however, the results are often irreproducible. We therefore aimed to meta-analyze three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a in intron 4, and T−786C (rs2070744) in promoter region, in association with hypertension from both English and Chinese publications, while addressing between-study heterogeneity and publication bias.MethodsData were analyzed using Stata software (version 11.0), and random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Publication bias was weighed using the Egger's test and funnel plot.ResultsThere were total 19284/26003 cases/controls for G894T, and 6890/6858 for 4b/a, and 5346/6392 for T−786C polymorphism. Overall comparison of allele 894T with 894G in all study populations yielded a 16% increased risk for hypertension (odds ratio [OR] = 1.16; 95% confidence interval [95% CI]: 1.07–1.27; P = 0.001), and particularly a 32% increased risk (95% CI: 1.16–1.52; P<0.0005) in Asians and a 40% increased risk (95% CI: 1.19–1.65; P<0.0005) in Chinese. Further subgroup analyses suggested that published languages accounted for the heterogeneity for G894T polymorphism. The overall OR of allele 4a versus 4b was 1.29 (95% CI: 1.13–1.46; P<0.0005) in all study populations, and this estimate was potentiated in Asians (OR = 1.42; 95% CI: 1.16–1.72; P<0.0005). For T−786C, ethnicity-stratified analyses suggested a significantly increased risk for −786C allele (OR = 1.25; 95% CI: 1.06–1.47; P = 0.007) and −786CC genotype (OR = 1.69; 95% CI: 1.20–2.38; P = 0.003) in Whites. As an aside, the aforementioned risk estimates reached significance after Bonferroni correction. Finally, meta-regression analysis on other study-level covariates failed to provide any significance for all polymorphisms.ConclusionWe, via a comprehensive meta-analysis, ascertained the role of eNOS G894T and 4b/a polymorphisms on hypertension in Asians, and T−786C polymorphism in Whites.