Investigating the genetic architecture of eye colour in a Canadian cohort
Researchers used data from 5,641 participants of European ancestry from the Canadian Partnership for Tomorrow’s Health (CanPath) and performed genome-wide association studies to investigate the genetic basis of eye color. The study identified multiple independent candidate causal variants in the HERC2/OCA2 region, along with single candidate variants near other genes such as IRF4, SLC24A4, TYR, and TYRP1. These findings suggest that eye color variation is influenced by specific molecular processes in iris melanocytes.
A statistical testing strategy accounting for random and nonrandom (skewed) X-chromosome inactivation identifies lung cancer susceptibility loci among smokers
The research used 9,261 participants from the CARTaGENE cohort to identify susceptibility loci for lung cancer among current and past smokers. X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 and rs12835699. For both SNPs, the minor allele was associated with lower lung cancer risk.
Premature thymic functional senescence is a hallmark of childhood acute lymphoblastic leukemia survivorship
The researchers investigated thymic immunosenescence in childhood acute lymphoblastic leukemia (cALL) survivors. The healthy participant cohort consisted of participants from the CARTaGENE cohort and an institutional cohort from the Centre Hospitalier de l’Université de Montréal. The thymic immunosenescence biomarker, signal joint T-cell receptor excision circles (TREC), was evaluated and was highly correlated with age in healthy participants and cALL survivors. While TREC levels declined with age in both groups, cALL survivors exhibited a systematic immunoage acceleration ranging from 5.9 to 88.3 years. This immunoage gain was independent of age at diagnosis and treatment modalities but was more pronounced in females and those with metabolic syndrome. The decline in TREC was unrelated to blood cell counts, suggesting selective thymic aging.
Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors
The researchers investigated pharmacodynamic biomarkers of response to pembrolizumab in 106 patients with advanced solid tumors. Researchers analyzed genome-wide methylation and fragment-length profiles using cfMeDIP-seq in 204 plasma samples from 87 patients. Two cohorts of normal control cfMeDIP-seq data, including 72 healthy women from the Ontario Health Study, were used for comparison. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. The study found that early kinetics of cancer-specific methylation (CSM) predicted overall survival and progression-free survival, independent of tumor type, PD-L1, and tumor mutation burden. The researchers’ tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.
Risk factors for early-onset colorectal cancer: A Canadian prospective cohort study
Researchers aimed to determine associations between specific risk factors and early-onset colorectal cancer (eoCRC). Accordingly, the researchers utilized data from 127,852 healthy study participants who were less than 50 years of age and were either part of the Ontario Health Study cohort or the Alberta’s Tomorrow Project cohort. Ninety-eight cases of eoCRC were identified after an average follow-up of 6.63 years. Analyses indicated that a family history of CRC alone or with a history of other cancer types was associated with a heightened risk of developing eoCRC. However, there was no significant association between eoCRC and a family history of solely non-CRC cancer. Those classified as heavy smokers at baseline had a higher risk of eoCRC compared to non-smokers. Lastly, there were no significant associations between sex, socioeconomic factors, diabetes, alcohol consumption, and other factors with the risk of eoCRC.
Neighbourhood walkability and greenspace and their associations with health-related fitness in urban dwelling Canadian adults
The researchers aimed to outline sex-specific associations between the neighborhood built environment, grip strength, and body fat percentage of Canadian adults living in urban areas. They used cohort data from 4,052 males and 7,841 females who were part of Alberta’s Tomorrow Project. Negative associations were found between walkability and both grip strength and body fat percentage among males and females. Additionally, greenness showed a positive association with grip strength across both sexes, but this association was not observed with body fat percentage. These associations remained significant even after adjusting for physical activity and sitting.
Polygenic inheritance and its interplay with smoking history in predicting lung cancer diagnosis: a French-Canadian casecontrol cohort
The researchers equipped a case-control dataset, consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from the CARTaGENE cohort. The researchers aimed to generate a genome-wide polygenic risk score for lung cancer to improve risk prediction and delineate individuals at high genetic risk of lung cancer for earlier detection and prevention.
The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: An individual participant data meta-analysis
Researchers investigated how various health behaviors might mediate the relationships between depression, anxiety, and the onset of different types of cancer. They conducted individual participant data meta-analyses using participants from 18 cohorts from the Psychosocial Factors and Cancer Incidence consortium.The cohorts analyzed included the Atlantic Partnership for Tomorrow’s Health, Ontario Health Study, and CARTaGENE. The findings suggested that smoking serves as a mediating factor that connects depression and anxiety with lung cancer and other cancers related to smoking.
Oral microbial signatures associated with age and frailty in Canadian adults
The researchers investigated the relationship between the oral microbiome, age, and frailty using data from Atlantic PATH cohort participants. Analyzing saliva samples from 1,357 individuals aged 35–70, they found that frailty was inversely associated with most alpha diversity measures, while age was positively associated with Shannon Diversity and Evenness. These findings suggest that the oral microbiome may be a valuable marker of frailty risk and a potential target for health interventions in aging adults.
The association between religiosity, spirituality and colorectal cancer screening: a longitudinal analysis of Alberta’s Tomorrow Project in Canada
The researchers performed a longitudinal analysis regarding associations between religion/spirituality (RS) Salience, and R/S Attendance, and colorectal cancer screening. The data of 4312 participants aged ≥ 50 from Alberta’s Tomorrow Project was used for this study. After completing statistical analyses, the researchers determined a significant association between R/S Attendance and colorectal cancer screening. However, R/S Salience did not contribute to higher odds of colorectal cancer screening, as the association was not statistically significant. The authors of the study propose the implementation of colorectal cancer screening programs in R/S settings.