Publications by authors named "Brigid Lynch"
Background: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Further, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)-positive breast cancer.
Methods: This was a case-cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study.
Background: Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.
Methods: Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls).
Epigenetic age quantifies biological age using DNA methylation information and is a potential pathway by which physical activity benefits general health. We aimed to assess the cross-sectional and longitudinal associations between physical activity and epigenetic age in middle-aged and older Australians. Blood DNA methylation data for 6208 participants (40% female) in the Melbourne Collaborative Cohort Study (MCCS) were available at baseline (1990-1994, mean age, 59 years) and, of those, for 1009 at follow-up (2003-2007, mean age, 69 years).
View Article and Find Full Text PDFBackground: Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT.
Methods: Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (n=30) or usual care (UC; n=32).
Article Synopsis
- * 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.
Background: Physical activity and sedentary behavior are associated with health outcomes. However, evidence may be affected by confounding bias. This study aimed to examine the relationships of physical activity and television (TV) viewing time with all-cause, cardiovascular, and cancer mortality in a cohort of Australian adults, and determine the robustness of these relationships to residual and unmeasured confounding.
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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.
Article Synopsis
- The study examined how different macronutrient intakes vary among adults based on their economic status and how these dietary patterns relate to health issues like central obesity and inflammation.* -
- Researchers analyzed data from over 41,000 US participants and identified four distinct dietary patterns, discovering that higher economic status correlates with diets rich in fats and proteins, while lower status is linked to higher saturated fat and low alcohol consumption.* -
- Findings revealed that a high saturated fat diet is associated with greater waist circumference and increased levels of inflammatory marker C-reactive protein, suggesting a link between economic status, dietary choices, and metabolic health.*
Evidence suggests that inflammation may be associated with a higher risk of endometrial cancer, but previous reviews have typically examined a limited number of biomarkers. This study aimed to critically appraise the evidence on the effect of 13 circulating inflammatory biomarkers on endometrial cancer risk. MEDLINE and EMBASE databases were searched for prospective cohort, (nested) case-control and case-cohort studies, and Mendelian randomization (MR) studies published up to 31 March 2023.
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- Folate intake plays a crucial role in genetic and metabolic processes, and low levels are linked to higher cancer risk, specifically colorectal cancer (CRC).
- The study analyzed dietary and supplemental folate intake among participants with CRC, investigating how this intake relates to specific genetic mutations using advanced sequencing techniques.
- Results indicated that higher total folate intake generally reduced CRC risk, but the impact varied when considering mutation status in tumors, with a few specific gene mutations showing different associations with folate intake.
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.
Article Synopsis
- Pancreatic cancer is the seventh leading cause of cancer deaths globally, and understanding modifiable risk factors like physical activity and sedentary behavior is crucial for prevention.
- A Mendelian randomization study analyzed genetic data to explore the relationship between physical activity, sedentary behavior, and pancreatic cancer risk using data from over 10,000 cases and 266,000 controls.
- The study found a causal link between increased television-watching time and higher pancreatic cancer risk, with BMI mediating about 54% of this effect, highlighting the importance of reducing sedentary behavior for cancer prevention.
Purpose: Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways.
Methods: This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study.
Background: Pre-diagnostic physical activity is reported to improve survival for women with breast cancer. However, studies of pre-diagnostic exposures and cancer survival are susceptible to bias, made clear when applying a target trial framework. We investigated the impact of selection bias, immortal time bias, confounding and bias due to inappropriate adjustment for post-exposure variables in a systematic review and meta-analysis of pre-diagnostic physical activity and survival after breast cancer.
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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: Performing physical activity may provide analgesic benefit, although this effect is more established for noncancer pain rather than cancer pain. The relationship between physical activity and pain outcomes in adults with and without a history of cancer was examined.
Methods: Totals of 51,439 adults without a cancer history and 10,651 adults with a cancer history from the Cancer Prevention Study II Nutrition Cohort were included.
Purpose: Physical activity can provide analgesic benefit but its effect on cancer-related pain is unclear. This review synthesised and appraised the evidence for the effect of physical activity on pain in people living with or beyond cancer.
Methods: A systematic search of Ovid Medline and Embase was performed to identify randomised controlled trials (RCTs), randomised cross-over studies (RXTs), and prospective observational studies that examined physical activity and pain outcomes in adults living with or beyond cancer.
Article Synopsis
- The genotoxin colibactin is linked to a specific mutation signature in colorectal cancer (SBS88), affecting tumor characteristics and possibly influencing risk and survival outcomes.
- A study involving over 4,300 tumors found that higher fruit intake lowers the risk of SBS88-positive colorectal cancer, and some epidemiological factors like BMI and alcohol consumption show different associations based on the presence of SBS88.
- While most risk and survival factors were similar regardless of SBS88 status, higher BMI might lead to worse survival outcomes for those with SBS88, suggesting a need for further research with more comprehensive genetic data.
Article Synopsis
- The study examined the connection between certain bacteria (pks E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum) and colorectal cancer (CRC) by analyzing DNA samples from various cohorts.
- Results revealed that pks E. coli is linked to male CRC patients and a specific APC gene mutation, mainly in early-onset cases, while F. nucleatum correlates with various cancer traits including DNA repair deficiencies and specific tumor locations.
- The findings suggest that pks E. coli might cause DNA damage related to the identified mutation, and F. nucleatum exists in both hereditary and sporadic factors of DNA mismatch repair deficiencies, highlighting the importance of the tumor environment for bacterial colon
Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal.
Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS).
Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.
Cancer Epidemiol Biomarkers Prev
March 2024
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.
Objectives: It was previously estimated that 1814 (1.6 % of incident cancers) were attributable to physical inactivity in Australia in 2010, when only three sites were considered. We estimated the burden of cancer due to physical inactivity in Australia for 13 sites.
View Article and Find Full Text PDFPurpose: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer.
Methods: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer.