Publications by authors named "Pellatt A"
Unlabelled: A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.
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- * A study identified a specific genetic variation at Chr6:31373718C>G that is associated with increased CRC risk, particularly in the younger population, with stronger odds for EOCRC compared to older adults.
- * Analysis showed that individuals carrying the minor G allele have reduced expression of the immune-related MICA gene and lower levels of Natural Killer (NK) cell infiltration in tumors, suggesting a link between this genetic variation and tumor immune response.
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.
Article Synopsis
- Research explored the link between calcium intake, genetic variants in the calcium sensor receptor gene, and survival rates in colorectal cancer (CRC) patients, using data from 18,952 individuals.
- No significant associations were found between dietary, supplemental, or total calcium intake and either all-cause or CRC-specific mortality, despite tracking 6,801 deaths over a median follow-up of 4.8 years.
- The study noted potential interactions between supplemental calcium intake and certain genetic variants, suggesting that genetics may influence how calcium affects mortality in CRC patients.
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.
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.
Ready, Set, Go: Setting Off on the Mission to Target in Colorectal Cancer.
JCO Oncol Pract
October 2024
Understanding the landscape of KRAS mutations in #CRC is crucial with over 2.8M annual diagnoses worldwide. Explore promising therapies and ongoing challenges in this comprehensive review.
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- Colorectal cancer (CRC) is a widely increasing disease linked to high body mass index (BMI), but the exact biological processes connecting these two factors are not well understood.
- The study employed Mendelian randomization to explore various biomarkers and lifestyle factors potentially mediating the impact of BMI on CRC risk, focusing on elements like inflammation, insulin levels, and physical activity.
- The findings indicated that higher genetically predicted BMI correlates with increased CRC risk, with evidence suggesting that the relationship might be partly mediated by plasma IGF1, while smoking and physical activity appear to complicate the association rather than mediate it.
Article Synopsis
- Appendiceal adenocarcinoma (AA) is a rare cancer with few treatment options, especially for patients who can't have surgery, leading researchers to test a combination therapy of atezolizumab and bevacizumab (Atezo+Bev).
- In a phase II study, the Atezo+Bev treatment demonstrated a 100% disease control rate and significantly longer progression-free survival (18.3 months) compared to traditional chemotherapy for colorectal cancer (4.4 months).
- The promising results suggest that Atezo+Bev could be an effective option for patients with unresectable AA, indicating a need for further research into this treatment approach.
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.
VivekSubbiah & colleagues delve into the @ASCO #TAPURStudy, shedding light on the importance of targeting ALL #BRAFAlterations, beyond V600E. (Re)-search continues, urging us to push the boundaries and unlock new possibilities in #PrecisionMedicine. #CancerResearch #JCOPO.
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- Obesity is linked to various types of colorectal cancer (CRC), but the strength and cause of these links are not fully understood.
- By using Mendelian randomization, researchers studied how body size traits like BMI, waist circumference, and body fat percentage affect risks for different CRC subtypes.
- Results showed that higher BMI and body fat significantly increased the risks for serrated and alternate CRC pathways (Jass types 1, 2, and 3), while associations with the traditional pathway (Jass type 4) were weaker.
Background: Traditional body-shape indices such as Waist Circumference (WC), Hip Circumference (HC), and Waist-to-Hip Ratio (WHR) are associated with colorectal cancer (CRC) risk, but are correlated with Body Mass Index (BMI), and adjustment for BMI introduces a strong correlation with height. Thus, new allometric indices have been developed, namely A Body Shape Index (ABSI), Hip Index (HI), and Waist-to-Hip Index (WHI), which are uncorrelated with weight and height; these have also been associated with CRC risk in observational studies, but information from Mendelian randomization (MR) studies is missing.
Methods: We used two-sample MR to examine potential causal cancer site- and sex-specific associations of the genetically-predicted allometric body-shape indices with CRC risk, and compared them with BMI-adjusted traditional body-shape indices, and BMI.
Article Synopsis
- People with cancer often face higher risks of developing venous thromboembolism (VTE), but the link between VTE and cancer risk isn't fully understood.
- A study used genetic data to examine whether VTE could be a risk factor for various cancers and vice versa, but found no strong causal connection.
- Although there was a slight association between VTE risk and pancreatic cancer, it was influenced by blood type and didn't indicate a direct cause-and-effect relationship; overall, the findings suggest that existing links between VTE and cancer are likely due to other factors related to cancer itself.
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.
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.
Background: People with cancer experience high rates of venous thromboembolism (VTE). Additionally, risk of subsequent cancer is increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer.
View Article and Find Full Text PDFAims/hypothesis: Epidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.
Methods: We developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program.
On the 25 March 2020 the Chief Dental Officer (CDO) published guidance to restrict the provision of routine dental care in England due to the rapid spread of the severe acute respiratory syndrome Coronavirus 2 (COVID-19). We analysed the impact of the pandemic on the number of patients presenting with odontogenic pain and infection to the emergency department (ED) of an urban-based teaching hospital, the Bristol Royal Infirmary (BRI). Furthermore, we investigated the severity of infection at first presentation to the ED.
View Article and Find Full Text PDFIntroduction: Tessier 30 facial cleft is a rare anomaly presenting in the soft and hard tissues over the central lower face. Owing to the rarity of cases and difficulty of treatment, there is no universally accepted surgical management strategy. The last comprehensive literature review of Tessier 30 clefts was in 1996.
View Article and Find Full Text PDFMidline clefts of the lower lip, tongue, and mandible are a rare type of facial cleft classified as "Tessier 30." We present the case of a female patient with an isolated Tessier 30 facial cleft affecting the tongue, lower lip, and mandibular symphysis with ankyloglossia. This was reconstructed with a template-guided resorbable "U"-shaped plate at 10 months of age.
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- - Obesity may lead to shorter telomeres due to increased oxidative stress and inflammation, impacting individuals throughout their lives.
- - A meta-analysis of 87 studies involving over 146,000 people revealed that each unit increase in BMI correlates with a significant decrease in telomere length, particularly among young adults.
- - The findings highlighted a stronger association of BMI with telomere length in the white population, with no notable differences observed between sexes.
Coronectomy procedures are widely carried out in secondary care, involving the removal of the dental crown, while retaining the roots in situ. This paper defines and explains the rationale behind coronectomy. It also seeks to review the indications for referral of wisdom teeth, and how to identify high-risk wisdom teeth radiographically using two- and three-dimensional imaging.
View Article and Find Full Text PDFBackground: The TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression.
Methods: In this study we comprehensively evaluate differential gene expression (RNASeq) of 81 genes in the TGFβ-signaling pathway and evaluate how dysregulated genes are associated with miRNA expression (Agilent Human miRNA Microarray V19.