Bin Zhu

• PhD
• Principal Investigator at National Cancer Institute (USA), National Institutes of Health

Understanding lung cancer evolution can identify tools for intercepting its growth. In a landscape analysis of 1024 lung adenocarcinomas (LUAD) with deep whole-genome sequencing integrated with multi-omic data, we identified 542 LUAD that displayed diverse clonal architecture. In this group, we observed an interplay between mobile elements, endogen...

Background Gastric cancer (GC), a molecularly heterogeneous disease, is the third leading cause of cancer death worldwide. The majority of GC cases worldwide occur in East Asia, predominantly China. Mutational Signature Framework offers an elegant approach to identify mutational processes present in tumors. Methods To identify mutational signature...

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful tool for cancer research, enabling in-depth characterization of tumor heterogeneity at the single-cell level. Recently, scRNA-seq copy number variation (scCNV) inference methods have been developed, expanding the application of scRNA-seq to study genetic heterogeneity in cancer using...

Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precanc...

Lung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure to secondhand tobacco smoke and air pollution in observational studies. Here, we evaluate the mutagenic exposures in LCINS by examining deep whole-genome sequencing data from a large international cohort of 871 treatment-naïve LCINS...

Lung cancer is the leading cause of cancer-related mortality worldwide. Understanding lung cancer evolutionary dynamics can help identify tools to intercept its growth and suggest strategies for treatment. Multiple factors can impact the tumors’ natural history and distinctly affect growth rate. However, research on the evolutionary trajectories of...

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B). However, how APOBEC3A/B enzymes shape the tumor evolution in th...

Waldenström macroglobulinemia (WM) is a rare hematological malignancy. Risk for WM is elevated 20-fold among first-degree relatives of patients with WM. However, the list of variants and genes that cause WM remains incomplete. In this study we analyzed exomes from 64 WM pedigrees for evidence of genetic susceptibility for this malignancy. We determ...

Some evidence suggests that pediatric sarcomas have both shared and distinct genetic profiles; however, large-scale efforts to characterize germline genetic susceptibility across these malignancies are limited by their rarity. We evaluated the role of common and rare variants in the genetic etiology of the more frequent pediatric sarcomas: osteosar...

Introduction. Emerging evidence suggests that the bacteria residing in colon and rectal tissue are plausibly associated with colorectal cancer (CRC). Prior studies investigated the effects of dietary interventions on the fecal microbiome but few assessed colorectal tissue microbiome endpoints. We investigated the effects of a high-fiber, high-fruit...

High-coverage sequencing allows the study of variants occurring at low frequencies within samples, but is susceptible to false-positives caused by sequencing error. Ion Torrent has a very low single nucleotide variant (SNV) error rate and has been employed for the majority of human papillomavirus (HPV) whole genome sequences. However, benchmarking...

Background and aims Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. Methods We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and BTC development. We categorized participants as non...

We evaluated whether aflatoxin B1 (AFB1) exposure was associated with later risk of developing gallbladder cancer (GBC). We measured AFB1‐lysine albumin adducts in baseline samples from the Shanghai Cohort Study of 18 244 men aged 45 to 64 years (recruited 1986‐1989). We included 84 GBC cases with sufficient serum and 168 controls matched on age at...

Tumor mutational signatures are important in clinical decision-making and are typically analyzed using whole exome or genome sequencing (WES/WGS). However, targeted sequencing is more commonly used in clinical settings, posing challenges in mutational signature analysis due to sparse mutation data and non-overlapping targeted gene panels. We introd...

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B). However, how APOBEC3A/B interact with exogenous mutagenic proce...

Mutational signatures, the footprints of somatic mutations, are associated with the causes of cancer and have been well-studied for tumors with whole exome or genome sequencing. However, due to the low number of detected mutations, mutational signatures were insufficiently explored for many tumors sequenced by targeted panels in clinics. It impedes...

Abstract Background Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associatio...

Background: Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs (nitro-PAHs), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and...

The use of publicly available sequencing datasets as controls (hereafter, “public controls”) in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we l...

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55–74 at enrollment in 1993–2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consen...

Background: The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue microbiome with adenoma recurrence in the Polyp Prevention Trial (PPT). Methods: PPT is a 4-year ra...

PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is a component of familial melanoma due to germline pathogenic variants (GPVs) in CDKN2A. However, it is unclear what role this gene or other genes play in its etiology. MATERIALS AND METHODS We analyzed 189 cancer predisposition genes using parametric rare-variant association (RVA) tests and nonpara...

Purpose: Chordoma is a rare bone tumor with a high recurrence rate and limited treatment options. The aim of this study was to identify molecular subtypes of chordoma that may improve clinical management. Experimental design: We conducted RNA sequencing in 48 tumors from Chinese skull-base chordoma patients and identified two major molecular sub...

Myelofibrosis is a rare myeloproliferative neoplasm (MPN) with high risk for progression to acute myeloid leukemia. Our integrated genomic analysis of up to 933 myelofibrosis cases identifies 6 germline susceptibility loci, 4 of which overlap with previously identified MPN loci. Virtual karyotyping identifies high frequencies of mosaic chromosomal...

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p.D57A) in an Italian melanoma...

Patients with severe aplastic anemia (SAA) can have an unrecognized inherited bone marrow failure syndrome (IBMFS) due to phenotypic heterogeneity. We curated germline genetic variants in 104 IBMFS-associated genes from exome sequencing performed on 732 patients who underwent HCT between 1989-2015 for acquired SAA. Patients with pathogenic/likely p...

Although multiple common susceptibility loci for lung cancer (LC) have been identified by genome-wide association studies (GWAS), they can explain only a small portion of heritability. The etiological contribution of rare deleterious variants (RDVs) to LC risk is not fully characterized and may account for part of the missing heritability. Here, we...

Chordoma is a rare bone tumor with genetic risk factors largely unknown. We conducted a whole‐exome sequencing (WES) analysis of germline DNA from 19 familial chordoma cases in five pedigrees and 137 sporadic chordoma patients and identified 17 rare germline variants in PALB2 and BRCA2, whose products play essential roles in homologous recombinatio...

For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requir...

Background Osteosarcoma is the most common primary bone malignancy. As a rare cancer, population‐based studies remain small with limited information on finer demographic categories. Recent studies have reported important genetic differences based on age and ethnicity, and more detailed studies are needed to better understand potentially important o...

Higher mammographic density (MD) is a known risk factor for breast cancer (BC), however, studies examining determinants of density in Chinese populations are limited. Asian women tend to have higher MD compared to European women, and yet they have a lower overall BC incidence rate. The goal of this study was to investigate the influence of establis...

The application of whole-exome sequencing (WES) has led to the identification of high and moderate-risk variants that contribute to cutaneous melanoma susceptibility. However, confirming disease-causing variants remains challenging. We applied a gene co-expression network analysis to prioritize candidate genes identified from WES of 34 melanoma-pro...

Recent genomic studies suggest that Asian breast cancer (BC) may have distinct somatic features, however, most comparisons of BC genomic features across populations did not account for differences in age, subtype, and sequencing methods. In this study, we analyzed whole-exome sequencing data to characterize somatic copy number alteration (SCNA) and...

Identifying cancer driver genes is essential for understanding the mechanisms of carcinogenesis and designing therapeutic strategies. Although driver genes have been identified for many cancer types, it is still not clear whether the selection pressure of driver genes is homogeneous across cancer subtypes. We propose a statistical framework MutScot...

Background To initiate fecal and oral collections in prospective cohort studies for microbial analyses, it is essential to understand how field conditions and geographic differences may impact microbial communities. This study aimed to investigate the impact of fecal and oral sample collection methods and room temperature storage on collection samp...

With the rapid advancement of sequencing technologies, next generation sequencing (NGS) analysis has been widely applied in cancer genomics research. More recently, NGS has been adopted in clinical oncology to advance personalized medicine. Clinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutati...

Background: It is important to identify inherited bone marrow failure syndromes (IBMFS) in patients with aplastic anemia in order to provide appropriate therapy. IBMFS are diagnosed through genetic or other diagnostic testing but can also go unrecognized, particularly in adults who may lack classic IBMFS features. This is particularly critical in l...

Introduction: Myelofibrosis (MF) is a rare myeloproliferative neoplasm (MPN) characterized by bone marrow fibrosis, progressive bone marrow failure, and increased risk of acute myeloid leukemia. While MF arises from somatic driver mutations in JAK2, MPL, and CALR, some MPN patients may have a heritable component. To comprehensively examine the gene...

PURPOSE Previous studies have shown an approximately two-fold elevation in the relative risk of urinary bladder cancer (UBC) among people with a family history that could not be entirely explained by shared environmental exposures, thus suggesting a genetic component in its predisposition. Multiple genome-wide association studies and recent gene pa...

Introduction Occupational diesel exhaust exposure has been linked to increased bladder cancer risk in epidemiologic studies, but few explore mechanistic links. Objectives We examined the relationship between diesel exhaust exposure and somatic mutations and mutational signatures in bladder tumors. Methods Targeted sequencing was conducted in blad...

Human papillomavirus (HPV) type 31 (HPV31) is closely related to the most carcinogenic type, HPV16, but only accounts for 4% of cervical cancer cases worldwide. Viral genetic and epigenetic variations have been associated with carcinogenesis for other high-risk HPV types, but little is known about HPV31. We sequenced 2093 HPV31 viral whole genomes...

Cigarette smoking and opium use are associated with periodontal disease caused by specific bacteria such as Porphyromonas gingivalis , which suggests a link between cigarette smoking and opium use and the oral microbiota. Alterations of the oral microbiota in cigarette smokers compared to nonsmokers have been reported, but this has not been studied...

PurposeIn addition to impacting incidence, risk factors for breast cancer may also influence recurrence and survival from the disease. However, it is unclear how these factors affect combinatorial biomarkers for aiding treatment decision-making in breast cancer.Methods Patients were 8179 women with histologically confirmed invasive breast cancer, d...

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline A...

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influe...

The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor–normal genomic DNA (gDNA) samples derived from a breast cancer cell line—w...

Background: Immune cell transcriptome signatures have been widely used to study the lung tumor microenvironment (TME). However, it is unclear to what extent the immune cell composition in the lung TME varies across histological and molecular subtypes (inter-tumor heterogeneity or Inter-TH) and within tumors (intratumor heterogeneity or ITH), and w...

For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requir...

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality, but is poorly characterized. Here we show, through high coverage whole genome sequencing of 232 tumors/blood pairs, that LCINS can be separated into three subtypes, defined by somatic copy number aberrations. While the dominant subtype (‘piano'), rarely found in lung cancer...

Elevated systemic levels of soluble cluster of differentiation 14 (sCD14) have been associated with gallbladder cancer (GBC), but the association with sCD14 levels within the gallbladder has not been investigated. Here, we evaluated sCD14 in the bile of 41 GBC cases and 117 gallstone controls with data on 65 bile inflammation markers. We examined t...

Background: Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains larg...

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations, we identified a novel NRAS variant (c.170A>C, p.D57A) in a melanoma-prone fam...

Purpose: Exome and whole-genome sequencing of muscle-invasive bladder cancer (BC) has revealed important insights into the molecular landscape; however, there are few studies of non-muscle invasive BC with detailed risk factor information. Experimental design: We examined the relationship between smoking and other BC risk factors and somatic mut...

A Correction to this paper has been published: https://doi.org/10.1038/s41375-021-01140-5

Objective: Zidovudine (ZDV) has been extensively used in pregnant women to prevent vertical transmission of human immunodeficiency virus (HIV), but few studies have evaluated potential mutagenic effects of ZDV during fetal development. Design: Our study investigated clonal hematopoiesis in HIV-exposed uninfected (HEU) newborns, 94 of whom were Z...

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1 , a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/...

Background Pediatric cancers are the leading cause of death by disease in children despite improved survival rates overall. The contribution of germline genetic susceptibility to pediatric cancer survivors has not been extensively characterized. We assessed the frequency of pathogenic/likely pathogenic (P/LP) variants in 5,451 long-term pediatric c...

Cellular aging in hematopoietic cell transplantation (HCT) is important in the context of immune reconstitution and age-related complications. Recently, several DNA-methylation (DNAm) based biomarkers of aging known as “epigenetic clocks” have been introduced as novel tools to predict cellular age. Here, we used Cox proportional hazards models to a...

Cancers arise owing to somatic mutations, and the characteristic combinations of somatic mutations form mutational signatures. Despite many mutational signatures being identified, mutational processes underlying a number of mutational signatures remain unknown, which hinders the identification of interventions that may reduce somatic mutation burde...

Background & Aims Gallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterize GBC and explore molecular subtypes associated with patient survival. Methods We profiled...

Epidemiological studies often rely on questionnaire data, exposure measurement tools, and/or biomarkers to identify risk factors and the underlying carcinogenic processes. An emerging and promising complementary approach to investigate cancer etiology is the study of somatic “mutational signatures” that endogenous and exogenous processes imprint on...

Although next-generation sequencing has demonstrated great potential for novel gene discovery, confirming disease-causing genes after initial discovery remains challenging. Here, we applied a network analysis approach to prioritize candidate genes identified from whole-exome sequencing analysis of 98 cutaneous melanoma patients from 27 families. Us...

Background Studies investigating associations between mammographic density (MD) and breast cancer subtypes have generated mixed results. We previously showed that having extremely dense breasts was associated with the HER2-enriched subtype in Chinese breast cancer patients. Methods In this study, we re-evaluated the MD-subtype association in 1,549...

Age-related DNA methylation is a potential mechanism contributing to breast cancer development. Studies of primarily Caucasian women have identified many CpG sites of age-related methylation in non-diseased breast tissue possibly driving cancer development over time. There is a paucity of studies involving Asian women whose ages at breast cancer on...

For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (selecting the number of mutational signatures through cross-validation), an unsupervised cross-validation method that requir...

p> Background: Epigenetic age, captured by DNA methylation changes, is thought to be more informative with respect to disease risk and progression, than chronological age. A few studies have associated epigenetic age acceleration (EAA), the difference between DNA methylation age (DNAm age) and chronological age, with BC risk and subtypes. However,...

PURPOSE Radiotherapy for childhood cancer is associated with elevated subsequent neoplasm (SN) risk, but the contribution of rare variants in DNA damage response and radiation sensitivity genes to SN risk is unknown. PATIENTS AND METHODS We conducted whole-exome sequencing in a cohort of childhood cancer survivors originally diagnosed during 1970...

It is challenging to identify somatic variants from high-throughput sequence reads due to tumor heterogeneity, sub-clonality, and sequencing artifacts. In this study, we evaluated the performance of eight primary somatic variant callers and multiple ensemble methods using both real and synthetic whole-genome sequencing, whole-exome sequencing, and...

We compared four different oral collection methods for studying the human oral microbiome: an OMNIgene ORAL kit, Scope mouthwash, nonethanol mouthwash, and Saccomanno’s fixative. Our study shows that the type of the collection method can have a large impact on the results of an oral microbiome analysis. We recommend that one consistent oral collect...

Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA meth...

Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD samples show substantial SCNA and methylation ITH, and c...

HPV35 has been found in only ∼2% of invasive cervical cancers (ICC) worldwide but up to 10% in Sub‐Saharan Africa, warranting further investigation and consideration of impact on preventive strategies. We studied HPV35 and ethnicity, in relation to the known steps in cervical carcinogenesis, using multiple large epidemiologic studies in the U.S. an...

Background: The oral microbiota may be associated with lung cancer risk through direct mechanisms, including infection, immune responses, and periodontal disease, and through indirect mechanisms such as the modification of the oral microbiota by tobacco. We conducted a case-cohort study nested within three US prospective cohort studies to evaluate...

Importance Osteosarcoma, the most common malignant bone tumor in children and adolescents, occurs in a high number of cancer predisposition syndromes that are defined by highly penetrant germline mutations. The germline genetic susceptibility to osteosarcoma outside of familial cancer syndromes remains unclear. Objective To investigate the germlin...

We develop a health informatics toolbox that enables public health workers to timely analyze and evaluate the time-course dynamics of the novel coronavirus (COVID-19) infection using the public available data from the China CDC. This toolbox is built upon a hierarchical epidemiological model in which two observed time series of daily proportions of...

HPV16 causes half of cervical cancers worldwide; for unknown reasons, most infections resolve within two years. Here, we analyze the viral genomes of 5,328 HPV16-positive case-control samples to investigate mutational signatures and the role of human APOBEC3-induced mutations in viral clearance and cervical carcinogenesis. We identify four de novo...

Severe aplastic anemia (SAA) is most frequently immune mediated, however, rare inherited bone marrow failure syndromes, such as Fanconi anemia (FA), may be causal, and can present as aplastic anemia (AA). FA is primarily an autosomal recessive disorder caused by having two pathogenic variants in a single FA/BRCA DNA repair pathway gene. Patients wi...

Background: Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and assoc...

Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). We investigated ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 LUAD patients. We found substantial SCNA and methylation ITH, and clonal architecture...

Background: Oral microbiota may be related to pancreatic cancer risk because periodontal disease, a condition linked to multiple specific microbes, has been associated with increased risk of pancreatic cancer. We evaluated the association between oral microbiota and pancreatic cancer in Iran. Methods: A total of 273 pancreatic adenocarcinoma cas...

Background: Biliary tract cancers (BTCs) are rare, but lethal cancers with a median survival of <12 months. Because of this poor prognosis, there is a critical need for treatments that extend survival. Cyclooxygenase-2 (COX-2) is an enzyme responsible for producing prostaglandin E (PGE). PGEs increase mucin production and reduce bile flow in the ga...

Exome and whole-genome sequencing of muscle-invasive (MI) bladder cancer has revealed important insights into the molecular landscape; however, there are few studies of non-muscle invasive (NMI) bladder cancer with detailed information on bladder cancer risk factors. We used deep, targeted amplicon sequencing of the coding regions of 44 genes frequ...

Globally, about 2 million people are diagnosed with lung cancer annually, making it the most common type of cancer in the world. In addition, lung cancer is the leading cause of cancer death among both men and women, accounting for ~25% of all cancer deaths in the United States and ~19% of cancer deaths worldwide. Although tobacco smoking is the mo...

Background: Known cutaneous malignant melanoma (CMM) genes account for melanoma risk in less than 40% of melanoma-prone families, suggesting the existence of additional risk genes or other modifiers. Whole exome sequencing (WES) of high-risk families usually results in the identification of a large number of potential disease-causing genes. However...

Globally, about 2 million people are diagnosed with lung cancer annually, making it the most common type of cancer in the world. In addition, lung cancer is the leading cause of cancer death among both men and women, accounting for ~25% of all cancer deaths in the United States and ~19% of cancer deaths worldwide. Although tobacco smoking is the mo...

p>Exome and whole-genome sequencing of muscle-invasive (MI) bladder cancer has revealed important insights into the molecular landscape; however, there are few studies of non-muscle invasive (NMI) bladder cancer with detailed information on bladder cancer risk factors. We used deep, targeted amplicon sequencing of the coding regions of 44 genes fre...

Background: Biliary tract cancers (BTCs) are rare, but lethal cancers with a median survival of <12 months. Because of this poor prognosis, there is a critical need for treatments that extend survival. Cyclooxygenase-2 (COX-2) is an enzyme responsible for producing prostaglandin E (PGE). PGEs increase mucin production and reduce bile flow in the ga...

Background Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% c...

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahe...

e13016 Background: Whole-genome sequencing (WGS) of formalin-fixed, paraffin-embedded (FFPE) samples could enable novel insights from archival sample collections, yet robust FFPE WGS is challenged by fragmented DNA, uneven genomic coverage & sequencing artifacts attributed to FFPE fixation. We report our proprietary extraction & library preparation...

10028 Background: Radiotherapy for childhood cancer is associated with strikingly elevated risk for developing subsequent neoplasms (SNs). Whether mutations in DNA repair and radiation sensitivity genes modulate SN risks is largely unknown. Methods: We conducted whole-exome sequencing in 5105 long-term childhood cancer survivors of European descent...