Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Northwestern China: a place to learn more on oesophageal cancer. Part two: gene alterations and polymorphisms.

International audienceIn the first part of this review, some behavioural and environmental risk factors playing important roles in the development of Kazakh's oesophageal squamous cell carcinoma (OSCC) were presented. Although all individuals have been exposed to the same environment and share the same behaviour, some of them will not develop OSCC. Thus, gene susceptibility and/or gene polymorphism are unavoidably involved. The molecular events underlying the initiation and progression of OSCC remain, however, poorly understood. In the second part of our review of OSCC in northwestern China, especially in the high-risk Kazakh population, some recent progress in the study of the molecular biology underlying oesophageal carcinogenesis, including chromosome deletions and loss of heterozygocity, polymorphisms of genes involved in xenobiotic metabolizing and DNA repair, and genetic alterations of transcriptional factors and apoptosis genes are presented. Results obtained in this high-risk population are compared with those obtained in other areas that are also known to be at high risk for OSCC, and whenever possible, with those studies performed in European, American or Australian low-risk areas. Recent advances in the investigation of the proteomics and microRNA biomarkers potentially useful for an earlier diagnosis and/or prognosis of OSCC are also discussed

A novel transfer-learning based physician-level general and subtype classifier for non-small cell lung cancer

Confirming histological patterns of lung carcinoma is important for determining the prognosis and the next steps of treatment for a patient. Confirming the histologic patterns (subtype) of lung adenocarcinoma is important for determining the prognosis and treatment options for a patient. The task is challenging, and often requires the input of experienced pathologists, who by themselves lack interobserver concordance. A computer-aided diagnosis holds the potential to accelerate the time to diagnosis. As many adenocarcinoma tissue samples contain multiple histologic patterns, accurate computer-aided diagnosis requires annotations manually labeled by pathologists. We propose a method that merges weak supervised learning and Integrated Learning using Transfer Learning using two datasets: The Cancer Genome Atlas (TCGA), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to reduce the need for manual annotation by a pathologist while maintaining accuracy. Whole-slide images (WSI) are first determined to be either adenocarcinoma or squamous cell carcinoma, then further identify the subtypes by generating weak classifiers for each subtype, then using integrated learning to create a strong classifier.Our model was evaluated with independent datasets from the CPTAC dataset and a dataset from a private hospital. It can achieve AUC values of 0.86, 0.91, 0.82, 0.77, 0.96, 0.98 in Acinar, LPA, Micropapillary, Papillary, Solid, and Normal, respectively

DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China

AIM: To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma (ESCC)

Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: A meta-analysis of genome-wide association studies

10.1093/hmg/dds029Human Molecular Genetics2192132-2141HMGE