About
1,000
Publications
89,934
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
45,211
Citations
Publications
Publications (1,000)
Background & Aims
Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have increased risk for hepatocellular carcinoma (HCC). However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European-descent populations (EDP).
Approac...
Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we p...
Genome-wide association studies (GWAS) have identified SNPs linked with lung cancer risk. Our aim was to discover the genes, non-coding RNAs, and regulatory elements within GWAS-identified risk regions that are deregulated in non-small cell lung carcinoma (NSCLC) to identify novel, clinically targetable genes and mechanisms in carcinogenesis. A tar...
Lung cancer is the leading cause of cancer-related death globally. An improved risk stratification strategy can increase efficiency of low-dose CT (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. On the basis of 13,119 patients with lung cancer...
The current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three SARS-CoV-2 host receptors (ACE2, DC-SIGN and L-SIGN) and DC status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of smokers, non-smokers and COVID-19 patients. We found smok...
Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conducted a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer(OCC)) and 5,256 controls. Four novel susceptibility loci wer...
Objective
To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules.
Design
We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantin...
Population stratification, or systematic differences in allele frequencies between subpopulations, can distort the results from genome-wide association studies (GWAS). While GWAS are usually conducted within continental (e.g. European) ancestry groups, sub-groups may have specific population histories that result in enrichment for risk or protectiv...
Background
Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when d...
Background
Genomic profiling of solid human tumors by projects such as The Cancer Genome Atlas (TCGA) has provided important information regarding the somatic alterations that drive cancer progression and patient survival. Although researchers have successfully leveraged TCGA data to build prognostic models, most efforts have focused on specific ca...
Lung cancer is the leading cause of cancer death worldwide. Genome-wide association studies have revealed genetic risk factors, highlighting the role of smoking, family history, telomere regulation, and DNA damage-repair in lung cancer etiology. Many studies have focused on a single ethnic group to avoid confounding from variability in allele frequ...
Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide asso...
Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1β pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic level. While numerous genome-w...
At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two‐sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological...
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 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355...
Background
Lung adenocarcinoma (LUAD) has become the most frequent histologic type of lung cancer in the past several decades. Recent successes with immune checkpoint blockade therapy have demonstrated that the manipulation of the immune system is a very potent treatment for LUAD. This study aims to explore the role of immune-related genes in the d...
Background
Cutaneous melanoma (CM) is the most lethal type of skin cancers. Nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in anabolic reactions and tumorigenesis, but many genes are involved in the NADPH system.
Methods
We used 10,912 single-nucleotide polymorphisms (SNPs) (2018 genotyped and 8894 imputed) in 134 NADP...
Background: Lung cancer (LC) survivors in the U.S. are increasing in number, with 5-year survival rates improving by 26% over the past decade. Although LC survivors are at high risk of developing a second primary lung cancer (SPLC), risk factors for SPLC have not been established and the impact of tobacco smoking remains controversial. In this stud...
p>More Americans die every year of lung cancer than any other cancer. While the environmental risks for lung cancer are well understood, the genetic risk factors for this disease are not, even though it has been shown that lung cancer risk aggregates in families. Segregation analyses have confirmed the likelihood of rare, highly penetrant variants...
p>Although cancer is a heterogeneous disease, there are shared hallmark mechanisms across multiple tumor types. Because of this, identifying genes associated with multiple cancer types has the potential to shed light on general oncogenic mechanisms. Conversely, integrating evidence for genetic association across multiple cancers could identify nove...
Introduction: Lung cancer is the leading cause of cancer-related deaths. 10% of never-smokers develop lung cancer. Currently, no genetic-based lung cancer screening tool exists. As a substitute, phenotypic traits can serve as surrogate markers for lung cancer risk. Our study focuses on identifying novel phenotypes associated with lung cancer. Genom...
Genome-wide association studies (GWAS) have revealed susceptible genetic risk factors for lung cancer, highlighting the role of smoking, family history, and DNA damage repair genes in disease etiology. Many studies have focused on European populations; however, lung cancer is a leading cause of cancer incidence and mortality around the world.
Previ...
Introduction: Prior epidemiological studies in glioma have identified 25 germline risk variants, as well as risk association with exposure to ionizing radiation and protective association with history of allergies and aspirin use. In this analysis we applied LDscore regression methods, which leverages single SNP associations and known patterns of l...
Genome-wide association studies (GWAS) have identified hundreds of common, low-penetrance alleles associated with cancer risk. However, known rare and common risk alleles only explain between 10% and 30% of the familial relative risk for different cancers and multiple lines of evidence indicate that many more risk alleles remain to be discovered. W...
About a fifth of individuals with colorectal cancer (CRC) present with disease metastasis at the time of diagnosis. While the role of the tumor microenvironment (TME) in governing CRC progression is undeniable, the role of the TME in either establishing or suppressing the formation of distant metastases of CRC is less well established. Despite adva...
It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene‐by‐environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power an...
Extensive studies have been conducted on the analysis of genome function, especially on the expression quantitative trait loci (eQTL). These studies offered promising results for characterization of the functional sequencing variation and understanding of the basic processes of gene regulation. Parent of origin effect (POE) is an important epigenet...
Genetics plays a role in age-related macular degeneration (AMD), a common cause of blindness in the elderly. There is a need for powerful methods for carrying out region-based association tests between a dichotomous trait like AMD and genetic variants on family data. Here we apply our new generalized functional linear mixed models (GFLMM) developed...
Background:
Lung cancer remains the leading cause of cancer death worldwide with 15-20% occurring in never-smokers. To assess genetic determinants for prognosis among never smokers, we conducted a genome-wide investigation in the International Lung Cancer Consortium(ILCCO).
Methods:
Genomic and clinical data from 1569 never-smoking lung cancer p...
We hypothesized that a joint analysis of cancer risk-associated SNP and somatic mutations in tumor samples can predict functional and potentially causal SNPs from GWASs. We used mutations reported in the Catalog of Somatic Mutations in Cancer (COSMIC). Confirmed somatic mutations were subdivided into 2 groups: (1) mutations reported as SNPs, which...
Observational studies have suggested that physical activity might lower the risk of lung cancer in former and current smokers, but not in never-smokers. Using genetic instruments for self-reported and accelerometer-measured physical activity traits implemented through two-sample Mendelian randomization (MR), we sought to strengthen the evidence for...
Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and under...
Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and under...
We hypothesized that human genes differ by their sensitivity to UV exposure. We used somatic mutations detected by genome‐wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer (COSMIC).
As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given tr...
It is unclear if genetic variants affect smoking cessation treatment response. This study tested whether variants in the cholinergic receptor nicotinic alpha 5 subunit (CHRNA5) predict response to smoking cessation medication by directly comparing two most effective smoking cessation pharmacotherapies. In this genotype-stratified randomized, double...
Acquired uniparental disomy (aUPD) regions pinpoint homozygousity and monoallelic expressed genes. We analyzed The Cancer Genome Atlas single-nucleotide polymorphism arrays and expression data from oral cavity, oropharynx, and larynx cancers to identify frequency of aUPD in each tumor type and association of aUPD regions and differentially expresse...
Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical region...
EGFR is an oncogene with a high frequency of activating mutations in nonsmall cell lung cancer (NSCLC). EGFR inhibitors have been FDA‐approved for NSCLC and have shown efficacy in patients with certain EGFR mutations. However, only 9% to 26% of these patients achieve objective responses. In our study, we developed an EGFR gene signature based on Th...
Background:
A substantial proportion of cancer driver genes (CDGs) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.
Methods:
We selected expression-related single nucleotide polymorphisms (eSNPs) and nonsynonymous variants of...
To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with P < 1 × 10−3 were further...
A few single‐nucleotide polymorphisms (SNPs) have been identified to be associated with cutaneous melanoma (CM) survival through genome‐wide association studies, but stringent multiple testing corrections required for the hypothesis‐free testing may have masked some true associations. Using a hypothesis‐driven analysis approach, we sought to evalua...
Background:
Cancer prognosis prediction is valuable for patients and clinicians because it allows them to appropriately manage care. A promising direction for improving the performance and interpretation of expression-based predictive models involves the aggregation of gene-level data into biological pathways. While many studies have used pathway-...
Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduc...
Lynch syndrome (LS), a hereditary cancer syndrome, accounts for approximately 3% of colorectal cancers (CRC). Positive health behaviors and surveillance are preventive strategies, but research on whether recommended behavioral guidelines are followed by individuals with LS is limited. Additional health education and promotion could be beneficial to...
Background:
Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cance...
Genome and transcriptome-wide association studies (GWAS and TWAS) have been successful in identifying genetic variants and candidate causal genes associated with lung cancer. However, systematic identification and functional studies of these genes remains a major bottleneck to clinical translation. Endogenous DNA damage has been implicated in genom...
BACKGROUND
Prior epidemiological studies in glioma have identified 25 germline risk variants, as well as risk associations with exposure to ionizing radiation (which increases risk) and history of allergies and aspirin use (which decrease risk). In this analysis we LDscore regression, which leverages single SNP associations and known patterns of li...
BACKGROUND
Genome-wide analyses estimate glioma heritability at 25%, yet known risk loci account for just one-third of this risk and suggest that sporadic glioma is a highly polygenic disease with hitherto unaccounted for genomic architecture. LD-score regression leverages results from genome-wide association studies (GWAS) and known patterns of li...
To investigate the role of tumor cytokines/chemokines in melanoma immune response, we estimated the proportions of immune cell subsets in melanoma tumors from The Cancer Genome Atlas, followed by evaluation of the association between cytokine/chemokine expression and these subsets. We then investigated the association of immune cell subsets, chemok...
We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung canc...
Acquired uniparental disomy (aUPD) leads to homozygosity facilitating identification of monoallelically expressed genes. We analyzed single-nucleotide polymorphism array-based genotyping data of 448 head and neck squamous cell carcinoma (HNSCC) samples from The Cancer Genome Atlas to determine the frequency and distribution of aUPD regions and thei...
Mutation of TP53 is the most frequent genetic alteration in high-grade serous ovarian cancer (HGSOC). The impact of hotspot mutations of TP53 and protein levels on patient outcomes in HGSOC has not been fully elucidated.
The study population (n = 791) comprised of HGSOC samples with TP53 mutation from TCGA and other publicly available data. Univari...
Genome-wide association study (GWAS)-identified single-nucleotide polymorphisms (SNPs) are tag SNPs located in both transcribed and noncoding regulatory DNA regions, rather than representing causal or functional variants for disease. To identify functional variants or genes for melanoma susceptibility, we used FUMA to perform functional annotation...
Genome‐wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies wit...
Background:
DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fu...
Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We address the computational burden encountered when detecting SNP...
Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when...
Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when...
Motivation:
Integration of multiple genetic sources for copy number variation detection (CNV) is a powerful approach to improve the identification of variants associated with complex traits. Although it has been shown that the widely used change point based methods can increase statistical power to identify variants, it remains challenging to effe...
Glutamine dependence is a unique metabolic defect seen in cutaneous melanoma (CM), directly influencing the treatment and prognosis. Here, we investigated the associations between 6025 common single‐nucleotide polymorphisms (SNPs) in 77 glutamine metabolic pathway genes with CM‐specific survival (CMSS) using genotyping datasets from two published g...
We analyzed summary-level data from genome-wide association studies (GWAS) of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) contributing to risk, as well as the distribution of their associated effect sizes. All cancers evaluated showed polygenicity, involving at a minimum tho...
Background: Lung cancer remains the leading cause of cancer mortality with relatively few prognostic biomarkers. We investigated associations with overall survival for telomere length (TL) and genetic variation in chromosome 5p15.33, an established telomere maintenance locus.
Methods: Leukocyte TL was measured after diagnosis in 807 patients with n...
Genome-wide association studies (GWAS) consisting of hundreds of thousands or millions of single nucleotide polymorphisms (SNPs) have presented the complex inheritance patterns of disease/trait. Although GWAS have identified thousands of SNPS associated with diseases, few studies have explored interactions among these SNPs that may influence diseas...
Lung cancer (LC) is the primary cause of cancer-related deaths in the United States. Whereas smoking and other environmental factors strongly increase LC risk, multiple genetic variants also contribute to risk in smokers. Furthermore, among smokers, some families have been identified with an abnormally high prevalence of LC, suggesting that unknown...
BACKGROUND: Approximately 5% of gliomas occur in individuals with a family history of glioma, and first-degree relatives of brain tumor cases have a two-fold increase in risk of brain tumor. Recent somatic characterization has shown that tumors from familial cases are indistinguishable from sporadic cases, suggesting that familial cases may arise t...
Background:
Genetic variation has an important role in the development of non-small-cell lung cancer (NSCLC). However, genetic factors for lung cancer have not been fully identified, especially in Chinese populations, which limits the use of existing polygenic risk scores (PRS) to identify subpopulations at high risk of lung cancer for prevention....
The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses...
BACKGROUND: Approximately 5% of gliomas occur in individuals with a family history of glioma, and first-degree relatives of brain tumor cases have a two-fold increase in risk of brain tumor. Recent somatic characterization has shown that tumors from familial cases are indistinguishable from sporadic cases, suggesting that familial cases may arise t...
Lung cancer (LC) is the primary cause of cancer-related deaths in the United States. Whereas smoking and other environmental factors strongly increase LC risk, multiple genetic variants also contribute to risk in smokers. Furthermore, among smokers, some families have been identified with an abnormally high prevalence of LC, suggesting that unknown...
Lung cancer (LC) kills more people in the United States each year than any other cancer. While it is well known that a variety of environmental factors (particularly tobacco smoke) strongly increase the risk of LC, there are multiple associated genetic variants with small contributions to risk. High aggregation of LC within rare individual families...
Genome-wide association studies (GWAS) consisting of hundreds of thousands or millions of single nucleotide polymorphisms (SNPs) have presented the complex inheritance patterns of disease/trait. Although GWAS have identified thousands of SNPS associated with diseases, few studies have explored interactions among these SNPs that may influence diseas...
Approximately 20% of colorectal cancer patients with colorectal adenocarcinomas present with metastases at the time of diagnosis, and therapies that specially target these metastases are lacking. We present a novel approach for investigating transcriptomic differences between primary colorectal adenocarcinoma and distant metastases, which may help...
Impaired lung function is an indicator of obstructive pulmonary disease and may be a consequence of cigarette smoking, making it challenging to disentangle its role in lung cancer etiology. We investigated the shared genetic basis of pulmonary dysfunction and lung cancer susceptibility using genome-wide data from the UK Biobank (>370,000 individual...
Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysi...
