Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

Quantile regression for survival data in modern cancer research:expanding statistical tools for precision medicin

Quantile regression links the whole distribution of an outcome to the covariates of interest and has become an important alternative to commonly used regression models.However,the presence of censored data such as survival time,often the main endpoint in cancer studies,has hampered the use of quantile regression techniques because of the incompleteness of data.With the advent of the precision medicine era and availability of high throughput data,quantile regression with high-dimensional predictors has attracted much attention and provided added insight compared to traditional regression approaches.This paper provides a practical guide for using quantile regression for right censored outcome data with covariates of low-or highdimensionality.We frame our discussion using a dataset from the Boston Lung Cancer Survivor Cohort,a hospital-based prospective cohort study,with the goals of broadening the scope of cancer research,maximizing the utility of collected data,and offering useful statistical alternatives.We use quantile regression to identify clinical and molecular predictors,for example CpG methylation sites,associated with high-risk lung cancer patients,for example those with short survival.

Antagonistic effect of early stage zinc on arsenic toxicity induced preterm birth during pregnancy:evidence from a rural Bangladesh birth cohort

To the Editor:Preterm birth(PTB),defined as livebirth before 37 completed weeks of gestation,is associated with a high degree of immaturity of various organs,and thus are at greater risk.of a range of short-term and long-term comorbidities.[1]The estimated PTB prevalence in Bangladesh,already among the highest at 19.1%,[2] is even higher in rural areas in Bangladesh,[3]posing a significant economic and emotional burden to these families and the country.