Publications by authors named "Virginia Diez-Obrero"

Gene expression appears altered in apparently normal tissue surrounding tumor tissue. The observed biological alterations in the tumor microenvironment play a crucial role in cancer development and are named the cancer field effect (FE). A robust set of overexpressed FE genes in tissue surrounding colorectal cancer (CRC) tumor were identified in previous studies.

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Background: Understanding genetic-metabolite associations has translational implications for informing cardiovascular risk assessment. Interrogating functional genetic variants enhances our understanding of disease pathogenesis and the development and optimization of targeted interventions.

Methods: In this study, a total of 187 plasma metabolite levels were profiled in 4974 individuals of European ancestry of the GCAT| Genomes for Life cohort.

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(1) Introduction: The global rise of gastrointestinal diseases, including colorectal cancer and inflammatory bowel diseases, highlights the need to understand their causes. Diet is a common risk factor and a crucial regulator of gene expression, with alterations observed in both conditions. This study aims to elucidate the specific biological mechanisms through which diet influences the risk of bowel diseases.

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  • 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.
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  • * 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.
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Obesity is a major risk factor for a myriad of diseases, affecting >600 million people worldwide. Genome-wide association studies (GWASs) have identified hundreds of genetic variants that influence body mass index (BMI), a commonly used metric to assess obesity risk. Most variants are non-coding and likely act through regulating genes nearby.

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  • 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.
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  • 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.
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  • Polygenic risk scores (PRS) can help identify individuals at higher risk for colorectal cancer (CRC), but current models based on European ancestry data don't perform well for non-European populations.
  • A study expands PRS development by adding Asian ancestry data alongside European data, resulting in improved predictive accuracy across diverse racial and ethnic groups in the US.
  • The findings emphasize the need for including more non-European ancestry populations to enhance risk prediction and ensure equitable clinical application of PRS in CRC prevention.
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  • 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.
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  • 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.!*
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  • Polygenic risk scores (PRS) can help target colorectal cancer (CRC) screening for those at higher risk, but current versions are less effective for non-European populations.
  • Researchers combined data from Asian ancestry with European ancestry datasets to improve PRS accuracy, achieving better performance across different racial/ethnic groups.
  • The study suggests that adding more non-European data, particularly from Black/African American and Latinx/Hispanic populations, is essential for enhancing risk prediction and promoting equitable clinical practices.
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  • 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.
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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.

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Colonomics is a multi-omics dataset that includes 250 samples: 50 samples from healthy colon mucosa donors and 100 paired samples from colon cancer patients (tumor/adjacent). From these samples, Colonomics project includes data from genotyping, DNA methylation, gene expression, whole exome sequencing and micro-RNAs (miRNAs) expression. It also includes data from copy number variation (CNV) from tumoral samples.

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  • 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.
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  • - 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.
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Background: Epidemiological studies have reported conflicting findings on the potential adverse effects of long-term antihypertensive medication use on cancer risk. Naturally occurring variation in genes encoding antihypertensive drug targets can be used as proxies for these targets to examine the effect of their long-term therapeutic inhibition on disease outcomes.

Methods And Findings: We performed a mendelian randomization analysis to examine the association between genetically proxied inhibition of 3 antihypertensive drug targets and risk of 4 common cancers (breast, colorectal, lung, and prostate).

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Ribosomes execute the transcriptional program in every cell. Critical to sustain nearly all cellular activities, ribosome biogenesis requires the translation of ~200 factors of which 80 are ribosomal proteins (RPs). As ribosome synthesis depends on RP mRNA translation, a priority within the translatome architecture should exist to ensure the preservation of ribosome biogenesis capacity, particularly under adverse growth conditions.

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  • Researchers conducted a genome-wide study on oropharyngeal cancer (OPC) and oral cavity cancer (OCC) using HPV16 serology status in a large sample size of 4,002 cancer cases and 5,256 controls.
  • They discovered four genetic susceptibility loci associated with HPV status, including two significant protective variants in the HLA region specifically linked to HPV-positive OPC risk.
  • The study suggests that these protective HLA variants enhance the immune response against HPV proteins, implying that vaccines targeting HPV components could potentially offer protection against HPV-positive OPC.
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Tobacco smoke and red/processed meats are well-known risk factors for colorectal cancer (CRC). Most research has focused on studies of normal colon biopsies in epidemiologic studies or treatment of CRC cell lines . These studies are often constrained by challenges with accuracy of self-report data or, in the case of CRC cell lines, small sample sizes and lack of relationship to normal tissue at risk.

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