Herbert Yu

Yale University | YU

Background: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. Methods: We conducted a genome-wide inte...

Background The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the developm...

Background: Alterations to DNA methylation have been identified in both hepatocellular carcinoma (HCC) tumor and circulating DNA from affected individuals. These markers have potential utility in HCC screening. Adherence to HCC screening is poor and acceptable HCC screening tests are needed. Methods: A feasibility study was performed on a subset of...

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-β pathway because...

Host immunity involves various immune cells working in concert to achieve balanced immune response. Host immunity interacts with tumorigenic process impacting disease outcome. Clusters of different immune cells may reveal unique host immunity in relation to breast cancer progression. CIBERSORT algorithm was used to estimate relative abundances of 2...

Pancreatic ductal adenocarcinoma (PDAC) is an uncommon but highly fatal malignancy. Identifying causal metabolite biomarkers offers an opportunity to facilitate effective risk assessment strategies for PDAC. In this study, we performed a two‐sample Mendelian randomization (MR) study to characterize the potential causal effects of metabolites in pla...

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we eval...

Background: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer (PC). Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for PC. Methods: Data from genome-wide association studies within the Pancrea...

Background: Previously studies shown a potential risk of antihypertensive medicines in relation to cancer susceptibility, which creating significant debate in the scientific community and public concern. We sought to investigate the relationship between antihypertensive medicines and cancer risk, by drug type and class. Methods: We conducted a p...

Background: Host immunity involves various immune cells working in concert to achieve balanced immune response. Host immunity interacts with tumorigenic process impacting disease outcome. Clusters of different immune cells may indicate specific host-tumor interplay. Identifying the clusters may reveal unique host immunity in response to tumor growt...

Background: The widespread use of antihypertensive drugs has raised concerns on whether the use increases the risk of cancer. Although multiple studies have addressed this issue, it remains unclear if hypertension patients who are on antihypertensive medications are at higher risk for cancer. Methods: Between 2013 and 2017, we enrolled 101,370 indi...

Purpose: HCC incidence, which is highest in Asians and Pacific Islanders (API), followed by Black/African Americans (AA), Hispanics (H), and non-Hispanic Whites (W), is rising at an alarming rate in the United States. Most HCC is diagnosed at an advanced incurable stage, emphasizing the need for accurate biomarkers for early diagnosis. The predicti...

Background Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. Methods We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the...

Purpose: Bladder cancer (BCa) is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. In previous studies, we and others have described the functional influence of plasminogen activator inhibitor-1 (PAI1) in bladder cancer development. While polymorphisms in PAI1 have been associated with increased risk...

Background: Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. Methods: We developed endometrial cancer risk prediction models...

Hepatocellular carcinoma (HCC) is the most common primary liver cancer whose incidence continues to rise in many parts of the world due to a concomitant rise in many associated risk factors, such as alcohol use and obesity. Although early-stage HCC can be potentially curable through liver resection, liver-directed therapies, or transplantation, pat...

Background PM 2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM 2.5 exposure, and aimed to find a potential intervention for people living in PM 2.5 polluted regions. Methods Elect...

Background Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. Materials and methods Data from 12 prospe...

Background: Hepatocellular carcinoma (HCC) is curable in its early stages. However, early stage HCC is difficult to detect without invasive surgical procedures. Additionally, current blood-based biomarkers have low sensitivity and specificity in detecting HCC. Human data and animal models support a functional role for the TGF-β pathway in HCC initi...

Background: Early detection of hepatocellular carcinoma (HCC) is challenging partly because most patients also have cirrhosis. Furthermore, patients with cirrhosis are at high risk of developing HCC. Loss of function of the transforming growth factor β (TGF-β) pathway is associated with HCC. The goal of this study was to determine if a reduction in...

Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a major cause of cancer death worldwide. Early detection is key to effective treatment. Yet, early diagnosis is challenging, especially in patients with cirrhosis, who are at high risk of developing HCC. Dysfunction or loss of function of the transforming growth factor β (TGF-β)...

Simple Summary ZNF582-AS1 expression is lower in breast cancer compared to adjacent normal tissues, and low expression is associated with poor disease-free and overall survival. Bioinformatic interrogation of ZNF582-AS1 expression and methylation signatures suggests the lncRNA’s involvement in cell cycle and cell death regulation. The lncRNA may ac...

Background and objectives Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate...

Among human genetic diseases, Fanconi Anemia (FA) tops all with its largest number of health complications in nearly all human organ systems, suggesting the significant roles played by FA genes in the maintenance of human health. With the accumulated research on FA, the encoded protein products by FA genes have been building up to the biggest cell...

Background and Aim Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in...

Background: Gut microbial alterations have been linked to chronic liver disease and hepatocellular carcinoma (HCC). The role of the oral microbiome in liver cancer development has not been widely investigated. Methods: Bacterial 16S rRNA sequences were evaluated in oral samples from 90 HCC cases and 90 controls who were a part of a larger U.S. c...

Background: PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions. Methods: PM2.5 w...

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-c...

Background Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. Objectives The objective of this study wa...

Background: Hepatocellular carcinoma (HCC) is the fastest rising cancer in the USA and is the fourth leading cause of cancer deaths globally. A critical unmet need to reduce high mortality associated with advanced HCC is the ability to identify high-risk individuals for cost-effective, targeted screening, early detection, and prevention strategies....

Background Endometrial cancer is the most common malignancy of the female reproductive system, and the third leading cause of cancer death among women. In contrast to other common cancers, endometrial cancer is one of the few caners with a rapidly increasing incidence rate but a decreasing survival rate. To date, genome-wide association studies (GW...

Globally, lung cancer ranks as the most lethal malignant neoplasm. d-Limonene, a plant extract enriched with essential oils, has been reported to exert anti-cancer effects both in vitro and in vivo; however, its clinical effect on humans remains elusive. Therefore, the present study aimed to investigate the gene expression signature that would pote...

Alternative splicing (AS) is a method of increasing the number of proteins that the genome is capable of coding for, by altering the pre-mRNA during its maturation. This process provides the ability of a broad range of proteins to arise from a single gene. AS events are known to occur in up to 94% of human genes. Cumulative data have shown that abe...

Objective We aimed to examine secular trends of thyroid cancer incidence and mortality and to estimate the proportion of thyroid cancer cases potentially attributable to overdiagnosis. Methods Data on thyroid cancer cases from 1973 to 2015 were obtained from Shanghai Cancer Registry. Average annual percent changes (AAPCs) were evaluated by Joinpoi...

Simple Summary Endometrial cancer is the leading female reproductive tract cancer in developed countries. Discovering new biomarkers is critical for understanding the etiology this cancer and identifying women with a higher risk of this cancer from the general population. Several blood protein biomarkers have been linked to endometrial cancer in pr...

Long non-coding RNAs (lncRNAs) have important biological functions, but their involvement in ovarian cancer remains elusive. We analyzed high-throughput data to identify lncRNAs associated with ovarian cancer outcomes. Our search led to the discovery of lncRNA TOPORS Antisense RNA 1 (TOPORS-AS1). Patients with high TOPORS-AS1 expression had favorab...

Background: The influence of sex hormone and insulin/insulin-like growth factor (IGF) axis signaling on endometrial cancer recurrence is unknown. We evaluated these pathways in a prospective cohort of Gynecologic Oncology Group (GOG)0210 trial endometrial adenocarcinoma patients. Methods: Stage II-IV patients (N=816) were included in this study....

Background: The mechanism of rapidly increased non-small cell lung cancer (NSCLC) among never-smoking Chinese women has not been elucidated. Ovarian sex steroid hormones have been suggested to counteract lung cancer development, and sex hormone-binding globulin (SHBG) is essential in sex hormones regulation. This study aims to exploring single nuc...

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative t...

Objective To explore the hypothesis that Citrus intake may reduce the risk of lung cancer. Design Meta-analyses of Dichotomy and dose-response relationship. Data sources We searched online literature databases including PubMed, Embase, and Cochrane Library to screen relevant articles available up to 27 July 2020. Search terms included (i) Citrus,...

Background: Many cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood. Methods: Association of SNP (rs140618127) in lncRNA LOC146880 with non-small cell lung cancer (NSCLC) was evaluated in a ca...

A full‐term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy‐related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case‐cont...

Background: Whether circulating polyunsaturated fatty acids (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies wi...

Significance Lung cancer is the most prevalent and deadly cancer worldwide. Minimally invasive testing for early detection of lung cancer is the key for improving prognosis. In this study, we carried out a multicenter, multiethnic study to compare the serum miRNA profiles between 744 NSCLC and 944 healthy controls. We discovered 35 candidate miRNA...

Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal malignancies with few known risk factors and biomarkers. Identification of disease biomarkers is critical for understanding the pathogenesis of this cancer and identifying high risk individuals for close surveillance. Several blood protein biomarkers have been linked to PDAC in previous...

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian rando...

Background Sleep disorder prevalence exhibited a six-fold relative increase from 2000 to 2010 in the United States. Sleep problems could increase the risk of stroke, cardiovascular disease, diabetes and cancer. Objective short sleep duration is associated with increased mortality. Obesity, smoking and sex differences could influence sleep disorders...

D-limonene a kind of natural extracts, obtained from citrus oils and found in common food items was reported to have anti-cancer effects and well-tolerated by cancer patients. While of interest as a cancer chemopreventive, the transcriptomic profile of limonene in humans is poorly understood. Based on transcriptomic profile result, a lncRNA named p...

Bile acids (BAs) play essential roles in facilitating lipid digestion and absorption in the intestine. Gastric BAs were attributed to abnormal refluxing from duodenal compartments and correlated with the occurrence of gastric inflammation and carcinogenesis. However, the differences in gastric BAs between physiologically compromised and healthy ind...

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated varian...

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P <...

We report a meta-analysis of breast, prostate, ovarian, and endometrial cancer genome-wide association data (effective sample size: 237,483 cases/317,006 controls). This identified 465 independent lead variants ( P <5x10 ⁻⁸ ) across 192 genomic regions. Four lead variants were >1Mb from previously identified risk loci for the four cancers and an ad...

Background: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. Methods: We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,...

Hepatocellular carcinoma (HCC) is an aggressive malignancy with its global incidence and mortality rate continuing to rise, although early detection and surveillance are suboptimal. We performed serological profiling of the viral infection history in 899 individuals from an NCI-UMD case-control study using a synthetic human virome, VirScan. We deve...

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers usually in small samples. In this study, we evaluated associations...

Background: BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal/ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of ind...

Genome-wide association studies (GWAS) have identified numerous genetic variants that are associated with lung cancer risk, but the biological mechanisms underlying these associations remain largely unknown. Here we investigated the functional relevance of a genetic region in 6q22.2 which was identified to be associated with lung cancer risk in our...

PurposeHCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case–control study in Connecticut, New Jersey and part of New York City.Methods Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on...

Background: Many previous studies reported secular trend of lung cancer incidence and mortality, but little is known about the possible reasons for these trends. Methods: Data were obtained from Shanghai Cancer Registry. Age-standardized rates were calculated and average annual percent changes (AAPCs) were evaluated by Joinpoint regression. Age,...

Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies (GWAS) in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we perform...

Background: Lung cancer is one of the leading diagnosed cancers worldwide, and microRNAs could be used as biomarkers to diagnose lung cancer. hsa-miR-195 has been demonstrated to affect the prognosis of NSCLC (non-small-cell lung cancer) in a previous study. However, the diagnostic value of hsa-miR-195-5p in lung cancer has not been investigated....

Silica nanoparticles (SiO2 NPs) are widely used in daily life and can enter organisms through several pathways, often causing unpredictable toxicity. Although SiO2 NPs are known to cause damage to the respiratory system, little is known about their oral toxicity, and their potential harm to the reproductive system is unclear. In this study, we used...

A nested case-control study was carried out using data from the United States Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 (341 women and 401 men) histologically co...

Introduction/Background In the Multiethnic Cohort (MEC) Study based in Hawaii and Los Angeles, the age-adjusted incidence of endometrial cancer (per 100,000, ages 60–90) is highest in Native Hawaiians (112.0) vs. 68.9 in white women. Since endometrial cancer develops under conditions of high circulating estrogen levels, we hypothesized that exposur...

Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lun...

Background and Purpose Ursodeoxycholic acid (UDCA) is the first‐line treatment for primary biliary cholangitis, but its effects on the enterohepatic circulation of bile acid (BA) have been under‐investigated. Therefore, we studied the influence of UDCA on BA enterohepatic circulation in vivo and the mechanisms by which UDCA affects the BA kinetics....

Introduction: MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs, consisting of about 20 nucleotides and studies have shown that miRNAs may play important roles in the development and progression of cancer. Members of the miR-30 family, including miR-30a, are reported to play different roles as oncogenes or tumor suppressor genes dependi...

Introduction: MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs, consisting of about 20 nucleotides and studies have shown that miRNAs may play important roles in the development and progression of cancer. Members of the miR-30 family, including miR-30a, are reported to play different roles as oncogenes or tumor suppressor genes dependi...

Purpose Low expression of long intergenic non-coding RNA LINC00472 in breast cancer is associated with aggressive tumors and unfavorable disease outcomes in multiple clinical datasets, but the reasons for these associations were unknown. Methods To study the mechanisms underlying the lncRNA’s connection to breast cancer, we investigated the molecu...

Background Rituximab is a chimeric IgG1 monoclonal antibody that depletes B cells for the treatment of several conditions including autoimmune diseases. It is not licensed for use in children but administered off-label. This study aimed to quantify the effect of rituximab on B cell depletion in children with autoimmune diseases and to optimise the...

The WW and C2 domain containing 1 gene encodes a protein named WWC1 (or KIBRA), which is involved in the Hippo signaling pathway. WWC1 is often lost in triple‐negative breast cancer and has been shown to suppress tumor metastasis. In this study, 470 breast cancer patients were recruited and WWC1 expression in the tumor samples were measured with qu...

5509 Background: Sex hormone and insulin/insulin-like growth factor (IGF) axis signaling pathways play an important role in endometrial cancer development but their role in endometrial cancer recurrence is unknown. In this study GOG-8015 we evaluated these pathways in a prospective cohort of patients diagnosed with the most common type of endometri...

Background: This study aimed to assess the relationship between specific nighttime-daytime sleep patterns and prevalence of different chronic diseases in an elderly population. Methods: We conducted a community-based cross-sectional study in 4150 elderly Chinese, with an average age of 74 years. Sleep-related variables (nighttime sleep duration,...

Background: Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and f...

Background It has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non‐coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non‐coding RNAs (lncRNAs) in non‐small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA ge...

Background Rituximab is a chimeric IgG-1 monoclonal antibody that depletes B cells, aiding in the treatment of several conditions including autoimmune and immunodeficiency diseases. It is not licensed for use in children but administered off-label. The current study aimed to identify the pharmacodynamics of rituximab in children with immune disorde...

Background Brain metastasis is an extremely serious sequela with a dismal prognosis in non-small cell lung cancer (NSCLC). The present study aimed to identify novel biomarkers and potential therapeutic targets for brain metastases of NSCLC. Methods We performed high-throughput Luminex assays to profile the transcriptional levels of 36 genes in 70...

Cigarette smoking plays an important role in the process of lung cancer, during which DNA damage is proved to be involved. Non-coding RNAs are found to be involved in the DNA damage and repair processes induced by cigarette smoke. In the present study, we investigated the role of lncRNA LCPAT1 in DNA damage caused by CSE in Beas-2B cells. Our resul...

The relative contribution of intrinsic genetic factors and extrinsic environmental ones to cancer aetiology and natural history is a lengthy and debated issue. Gene–environment interactions (G x E) arise when the combined presence of both a germline genetic variant and a known environmental factor modulates the risk of disease more than either one...

Background Hepatic encephalopathy (HE), a severe neuropsychiatric complication, is associated with increased blood levels of ammonia and bile acids (BAs). We sought to determine (1) whether abnormally increased blood BAs in liver cirrhotic patients with HE is caused by elevation of apical sodium-dependent BA transporter (ASBT)-mediated BA reabsorpt...