Publications by authors named "Keku T"

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.
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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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Background And Aims: Microscopic colitis (MC) is a common cause of chronic diarrhea; however, the clinical course of this disease is poorly understood. We aimed to investigate how patients diagnosed with MC were treated in routine clinical practice and how their symptoms compared to patients with other causes of chronic diarrhea at one year follow-up.

Methods: We conducted a case-control study of patients undergoing outpatient colonoscopy to evaluate diarrhea.

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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.

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The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022.

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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.
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  • Colonic diverticulosis is a common condition in older adults characterized by thin-walled pockets in the colon that can lead to inflammation, infection, and other complications, prompting a study to explore its genetic basis.
  • A case-control study analyzed DNA and RNA from colonic tissue of 404 patients (172 with diverticulosis and 232 without) to understand the transcriptomic variations linked to the condition.
  • The findings revealed 38 differentially expressed genes and pointed to tissue remodeling involving various cell types in the colon as a key factor in diverticula formation, with genetic predispositions influencing the severity of the condition.
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Background: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.

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  • 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.
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Background: The association of fitness with cancer risk is not clear.

Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.

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Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and its incidence and mortality are rising. Obesity is more tightly associated with EC than any other cancer. Thus, the rising prevalence of obesity and associated risk factors, including diabetes and insulin resistance, cause alarm.

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Article Synopsis
  • 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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Unlabelled: Fusobacterium nucleatum (Fn) has been frequently detected in colorectal cancer. A high load of Fn has been associated with subtypes of colorectal cancers, located in the proximal colon, exhibiting microsatellite instability-high (MSI-H), MLH1 promoter hypermethylation, the CpG island hypermethylation phenotype-high, or BRAF mutation in some studies. Although these features characterize the sessile serrated pathway (SSP) of colon cancers, other studies have shown that Fn infection is associated with KRAS mutations mainly characteristic of non-serrated neoplasia.

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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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Background: Microscopic colitis (MC) is an increasingly common cause of watery diarrhea particularly in older individuals. The role of diet in MC has received little study.

Methods: We conducted a case-control study at a single institution enrolling patients referred for elective outpatient colonoscopy for diarrhea.

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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.!*
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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.
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The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results.

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Introduction: Patients with alpha-gal syndrome, a delayed reaction to mammalian meat, can present with isolated gastrointestinal (GI) symptoms. We aimed to estimate the frequency of alpha-gal sensitization in a Southeastern US population and determine the association between sensitization and mammalian product dietary intake or GI symptoms.

Methods: We performed a cross-sectional study of participants who underwent a screening colonoscopy at our center between 2013 and 2015.

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Article Synopsis
  • 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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Background: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.

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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.
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