Publications by authors named "Stephanie Bien"

Article Synopsis
  • Colorectal cancer (CRC) is a major health concern, and understanding how genetic and environmental factors interact can help identify at-risk groups.
  • This study analyzed data from over 45,000 CRC cases to assess both multiplicative and additive interactions between genetic risk scores and various environmental factors, finding no multiplicative interactions but significant additive ones for high genetic susceptibility individuals.
  • Results suggest that individuals with high genetic risk could benefit more from lifestyle interventions like reducing alcohol intake or increasing fruit and fiber consumption, emphasizing the need for targeted prevention strategies in CRC care.
View Article and Find Full Text PDF
Article Synopsis
  • * Researchers analyzed data from 52 studies, including nearly 31,000 CRC cases and over 41,000 controls, to explore the genetic interactions with regular aspirin/NSAID use.
  • * They found significant interactions with genetic variants in two specific regions (6q24.1 and 5p13.1), which could help uncover new targets for understanding how aspirin provides its protective effects against colorectal cancer.
View Article and Find Full Text PDF
Article Synopsis
  • Consumption of fiber, fruits, and vegetables may lower the risk of colorectal cancer (CRC), but genetic factors might influence this connection.
  • A large study involving nearly 70,000 participants identified two significant genetic variants linked to dietary intake and CRC risk using advanced statistical methods.
  • The findings suggest specific genetic loci (SLC26A3 and NEGR1) may affect how fiber and fruit consumption interacts with CRC risk, highlighting the need for more research on the underlying mechanisms.
View Article and Find Full Text PDF

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

View Article and Find Full Text PDF
Article Synopsis
  • Menopausal hormone therapy (MHT) may lower the risk of colorectal cancer (CRC), especially in women with a higher genetic predisposition to the disease.
  • In a study of nearly 30,000 postmenopausal women, those in the highest genetic risk quartile saw a significantly greater reduction in CRC risk when using MHT compared to those in the lowest quartile.
  • The findings suggest that integrating genetic risk information could improve CRC risk predictions and inform the assessment of MHT benefits in postmenopausal women.
View Article and Find Full Text PDF
Article Synopsis
  • High consumption of red and processed meats is linked to an increased risk of colorectal cancer, with a study analyzing data from over 29,000 cancer cases and 39,000 control subjects confirming this association.
  • The research identified two significant genetic markers (SNPs) that interact with meat consumption levels, suggesting that certain genetic variants can influence individual cancer risk based on dietary habits.
  • These findings highlight the potential for using genetic information to better understand colorectal cancer risks related to diet, which may lead to personalized dietary recommendations for specific population subgroups.
View Article and Find Full Text PDF
Article Synopsis
  • A study is exploring how genetic variations might influence the relationship between folate intake and colorectal cancer risk, focusing on specific genetic interactions.
  • The research analyzed data from over 30,000 colorectal cancer cases and 42,000 controls, examining the effects of dietary folate and folic acid supplements.
  • Results indicated that while higher folate intake is generally linked to lower CRC risk, certain genetic variants (like rs150924902) can modify this effect, with some genotypes showing increased risk with folate supplementation.
View Article and Find Full Text PDF
Article Synopsis
  • Diabetes is linked to a higher risk of colorectal cancer, but the mechanisms behind this link and the influence of genetic variants need further exploration.!* -
  • Researchers conducted a genome-wide analysis using data from over 31,000 colorectal cancer cases and nearly 41,500 controls to investigate gene-environment interactions involving genetics and diabetes.!* -
  • Findings revealed that specific genes on chromosomes 8q24.11 (SLC30A8) and 13q14.13 (LRCH1) may affect how diabetes increases colorectal cancer risk, highlighting potential biological pathways related to insulin signaling and immune functions.!*
View Article and Find Full Text PDF
Article Synopsis
  • This study explores how genetics and body mass index (BMI) interact to influence colorectal cancer risk, analyzing data from over 84,000 participants.
  • The research identifies a significant genetic marker (rs58349661) in the FMN1/GREM1 gene region that shows a strong connection with increased cancer risk in individuals with higher BMI, particularly among those with a specific genotype.
  • Findings suggest that understanding this gene-environment interaction could help develop more tailored prevention strategies for colorectal cancer related to obesity.
View Article and Find Full Text PDF
Article Synopsis
  • Tobacco smoking increases the risk of colorectal cancer, and certain genetic profiles may heighten this risk further.
  • A study involving over 33,000 colorectal cancer cases and nearly 44,000 controls identified specific genetic loci (on chromosomes 3p12.1, 6p21.33, and 8q24.23) that interact with smoking behaviors, potentially leading to a greater risk of developing the disease.
  • The research suggests that higher expression of specific genes is associated with a lower risk of colorectal cancer, emphasizing the role of these genetic factors in smoking-related cancer susceptibility and potential avenues for prevention.
View Article and Find Full Text PDF

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues.

View Article and Find Full Text PDF

The BCG (Bacille Calmette-Guérin) vaccine, introduced 100 years ago for tuberculosis prevention, has emerging therapeutic off-target benefits for autoimmunity. In randomized controlled trials, BCG vaccinations were shown to gradually improve two autoimmune conditions, type 1 diabetes (T1D) and multiple sclerosis. Here, we investigate the mechanisms behind the autoimmune benefits and test the hypothesis that this microbe synergy could be due to an impact on the host T cell receptor (TCR) and TCR signal strength.

View Article and Find Full Text PDF

Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (G × E) interactions and may provide information on the underlying biological pathway.

View Article and Find Full Text PDF
Article Synopsis
  • The study explored how menopausal hormone therapy (MHT) interacts with genetic variants to affect the risk of colorectal cancer (CRC) in 28,486 postmenopausal women.
  • Results indicated that MHT use was linked to a lower risk of CRC, with specific genetic variants playing a significant role in this association.
  • The findings suggest that understanding these genetic interactions could lead to deeper insights into CRC development and potential therapeutic strategies.
View Article and Find Full Text PDF
Article Synopsis
  • - The study investigates the genetic and environmental interactions influencing colorectal cancer risk, focusing on the J-shaped relationship with alcohol consumption, distinguishing between nondrinkers, light-to-moderate drinkers, and heavy drinkers.
  • - By pooling data from major cancer registries, the researchers identified 13 significant SNPs in the 10q24.2/COX15 region, showing that the A allele of SNP rs2300985 increases colorectal cancer risk for light-to-moderate drinkers compared to nondrinkers and heavy drinkers.
  • - The findings suggest that the strongest genetic association with colorectal cancer occurs in nondrinkers, with SNP rs1318920 predicted as a potential causal regulatory variant impacting cancer risk.
View Article and Find Full Text PDF

One mechanism by which genetic factors influence complex traits and diseases is altering gene expression. Direct measurement of gene expression in relevant tissues is rarely tenable; however, genetically regulated gene expression (GReX) can be estimated using prediction models derived from large multi-omic datasets. These approaches have led to the discovery of many gene-trait associations, but whether models derived from predominantly European ancestry (EA) reference panels can map novel associations in ancestrally diverse populations remains unclear.

View Article and Find Full Text PDF

Aims/hypothesis: Type 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes, glycaemic traits and insulin-related traits.

View Article and Find Full Text PDF

Hematological measures are important intermediate clinical phenotypes for many acute and chronic diseases and are highly heritable. Although genome-wide association studies (GWAS) have identified thousands of loci containing trait-associated variants, the causal genes underlying these associations are often uncertain. To better understand the underlying genetic regulatory mechanisms, we performed a transcriptome-wide association study (TWAS) to systematically investigate the association between genetically predicted gene expression and hematological measures in 54,542 Europeans from the Genetic Epidemiology Research on Aging cohort.

View Article and Find Full Text PDF

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the gene (rs11466334, risk allele frequency (RAF) = 6.

View Article and Find Full Text PDF

Hodgkin lymphoma (HL) Reed Sternberg cells express tumor-associated antigens (TAA) that are potential targets for cellular therapies. We recently demonstrated that TAA-specific T cells (TAA-Ts) targeting WT1, PRAME, and Survivin were safe and associated with prolonged time to progression in solid tumors. Hence, we evaluated whether TAA-Ts when given alone or with nivolumab were safe and could elicit antitumor effects in vivo in patients with relapsed/refractory (r/r) HL.

View Article and Find Full Text PDF

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Moreover, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed.

Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including = 229 African American and = 381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, = 922 European ancestry participants, whole blood).

View Article and Find Full Text PDF

Background: Circulating white blood cell and platelet traits are clinically linked to various disease outcomes and differ across individuals and ancestry groups. Genetic factors play an important role in determining these traits and many loci have been identified. However, most of these findings were identified in populations of European ancestry (EA), with African Americans (AA), Hispanics/Latinos (HL), and other races/ethnicities being severely underrepresented.

View Article and Find Full Text PDF
Article Synopsis
  • Understanding the diverse causes of colorectal cancer (CRC) is essential for developing tailored prevention and treatment strategies, as tumors in different locations may develop through distinct mechanisms.
  • A genome-wide association study involving over 48,000 CRC cases revealed 13 new specific risk loci linked to CRC, highlighting significant differences in genetic factors between tumors in the proximal (early) and distal (later) regions of the colorectum.
  • The findings indicate that the genetic risk factors for proximal and distal CRC are different, suggesting that prevention and treatment strategies should be tailored based on the tumor's anatomical location.
View Article and Find Full Text PDF