Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P < 0.05). Moreover, the 10.4% (8/77) of individuals with mismatch repair (MMR) VUS had a higher tumor mutational burden (TMB), although the correlation was not significant.Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC

Polymorphisms of the _ENPP1_ gene are not associated with type 2 diabetes or obesity in the Chinese Han population

*Objective:* Type 2 Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and with a major feature of insulin resistance. Genetic association studies have suggested that _ENPP1_ might play a potential role in susceptibility to type 2 diabetes and obesity. Our study aimed to examine the association between _ENPP1_ and type 2 diabetes and obesity.

*Design:* Association study between two SNPs, rs1044498 (K121Q) and rs7754561 of ENPP1 and diabetes and obesity in the Chinese Han population.

*Subjects:* 1912 unrelated patients (785 male and 1127 female with a mean age 63.8 ± 9 years), 236 IFG/IGT subjects (83 male and 153 female with a mean age 64 ± 9 years) and 2041 controls (635 male and 1406 female with a mean age 58 ± 9 years).
 
*Measurements:* Subjects were genotyped for two SNPs using TaqMan technology on an ABI7900 system and tested by regression analysis.

*Results:* By logistic regression analysis, rs1044498 (K121Q) and rs7754561 showed no statistical association with type 2 diabetes, obesity under additive, dominant and recessive models either before or after adjusting for sex and age. Haplotype analysis found a marginal association of haplotype C-G (p=0.05) which was reported in the previous study.

*Conclusion:* Our investigation did not replicated the positive association found previously and suggested that the polymorphisms of _ENPP1_ might not play a major role in the susceptibility to type 2 diabetes or obesity in the Chinese Han population

Association of Genetic Loci with Blood Lipids in the Chinese Population

Recent genome-wide association (GWA) studies have identified a number of novel genetic determinants of blood lipid concentrations in Europeans. However, it is still unclear whether these loci identified in the Caucasian GWA studies also exert the same effect on lipid concentrations in the Chinese population. showed modest association with triglyceride in the Chinese population. in plasma lipid and lipoprotein concentrations in Chinese population

Association of the CHRNA3 Locus with Lung Cancer Risk and Prognosis in Chinese Han Population

IntroductionRecent genome-wide association studies in Caucasians revealed association with lung cancer risk of single nucleotide polymorphisms (SNPs) in the locus containing two nicotine acetylcholine receptor CHRNA genes. However, the reported risk SNPs are extremely rare in Asians. This study sought to identify other variants on CHRNA3 associated with lung cancer susceptibility and to explore whether SNPs of CHRNA3 are of prognostic factors in patients with non-small cell lung cancer (NSCLC) in Chinese Han population.MethodsA case-control study of 529 cases and 567 controls was performed to study the association of three SNPs (rs3743076, rs3743078, and rs3743073) in CHRNA3 with lung cancer risk in Chinese Han population using logistic regression models. The relationship between CHRNA3 polymorphisms with overall survival among 122 patients with advanced stage (stage IIIb and IV) NSCLC were evaluated using Cox multiple model based on the International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.ResultsPatients with genotypes TG or GG for the novel SNP rs3743073 in CHRNA3 gene, compared with those with TT, showed an increased risk of lung cancer (adjusted odds ratio = 1.91; 95% confidence interval, 1.38–2.63; p = 9.67 × 10−5) and worst survival (adjusted hazard ratio = 2.35; 95% confidence interval, 1.05–5.26; p = 0.04) in patients with advanced stage NSCLC based on International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.ConclusionsThese results suggest that the rs3743073 polymorphism in CHRNA3 is predictive for lung cancer risk and prognostic in advanced stage NSCLC in Chinese Han population

How Can the European Federation for Colposcopy Promote High Quality Colposcopy Throughout Europe?

Since its inception in 1998, the European Federation for Colposcopy (EFC) now comprises 26 member societies. Its principle aim is to promote high quality colposcopy throughout Europe with special emphasis on training, education and treatment. This review summarises EFC’s activities and achievements to date

Retraction Note: Identification of de Novo Mutations in Prenatal Neurodevelopment-Associated Genes in Schizophrenia in Two Han Chinese Patient-Sibling Family-Based Cohorts (Translational Psychiatry, (2020), 10, 1, (307), 10.1038/s41398-020-00987-Z)

© 2020, The Author(s). This article1 has been retracted at the request of Authors Xingwang Li and Lin He. After publication, it was realized that approval to use data from the NSFC-NIH Sino-US cooperation project (Project No. 81361120389) was not obtained from the data owners. Authors Dongmei Cao, Xiangning Chen, Lin He, Kenneth Kendler, Xingwang Li, Travis Mize, Chunling Wan and Jain-Shing Wu agree to this retraction. Authors Shan Jiang, Jingchun Chen and Zongming Zhao do not agree to this retraction. Authors Guang He, Peilin Jia, Xiaoqian Jiang, Yimei Lu, Ming Tsuang, Yin-Ying Wang and Daizhan Zhou did not respond to correspondence from the Publisher about this retraction

The Preoperative Prognostic Nutritional Index in Hepatocellular Carcinoma After Curative Hepatectomy: A Retrospective Cohort Study and Meta-Analysis

Objective Conflicting results existed about the role of prognostic nutritional index (PNI) for hepatocellular carcinoma (HCC) patients who received curative hepatectomy. The aim of this study is to identify the predictive capacity of PNI for survival after hepatectomy. Methods Preoperative PNI, neutrophil-to-lymphocyte ratio (NLR), tumor feature and clinical information of 187 patients with HCC from Sir Run Run Shaw hospital were evaluated. We also conducted a meta-analysis of seven cohort studies. Results Our study showed that HCC patients with a low PNI of <45 had a poor recurrence-free survival (RFS) rate (hazard ratio [HR] 1.762, 95% confidence interval [CI] 1.066–2.911, p = 0.027, respectively). The 5-year OS and RFS rates of the high PNI (≥45) vs low PNI (<45) were 76.7% vs 50.1% (p = 0.001) and 47.0% vs 28.9% (p = 0.001), respectively. In HCC TNM I patients (n = 144), a low PNI remained an independent prognostic factor of OS and RFS (HR 2.305, 95% CI 1.008–5.268, p = 0.048; HR 2.122, 95% CI 1.149–3.920, p = 0.016). The 5-year OS and RFS rates of the high PNI vs low PNI were 81.3% vs 62.4% (p = 0.041) and 53.4% vs 45.6% (p = 0.013), respectively. In the pooled analysis, the data showed that a low PNI was significantly associated with poor OS and RFS (HR 2.27, 95% CI 1.03–4.07, p < 0.001 and HR 1.68, 95% CI 1.45–1.94, p < 0.001, respectively). Conclusions The preoperative PNI was an independent prognostic factor for OS and RFS rates in HCC patients who received hepatectomy

Association of Serum Antioxidant Minerals and Type 2 Diabetes Mellitus in Chinese Urban Residents

Antioxidant minerals including zinc, copper and selenium play critical roles in the maintenance of the redox balance in the body. However, their influences on type 2 diabetes mellitus (T2DM) are still inconclusive in Chinese populations. To elucidate the relationship between antioxidant minerals and T2DM, serum zinc, copper and selenium concentrations were measured in 1443 Chinese urban residents using a 1:2 matched case-control study. Conditional logistic regression models (CLR) were used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs), and restricted cubic splines (RCS) were used to examine their dose–response associations. Serum zinc (OR = 0.52 [0.35, 0.77]) and copper concentrations (OR = 0.25 [0.17, 0.37]) were negatively associated with T2DM in a fully adjusted model. An L-shaped zinc-T2DM association (Poverall association = 0.003, and Pnonlinearity = 0.005) and a negative linear copper-T2DM association (Poverall association Pnonlinearity = 0.395) were observed. No association was found between serum selenium and T2DM in fully adjusted CLR or RCS models. In addition, joint associations with T2DM were identified between serum zinc and copper and between serum selenium and copper. In conclusion, our study emphasizes the importance of an adequate intake of antioxidant minerals for T2DM prevention in the Chinese population