Toenail arsenic species and metallome profiles associated with breast, cervical, prostate, and skin cancer prevalence in the Atlantic Partnership for Tomorrow’s Health cohort

Authors: Kalli Hood, Ellen Sweeney, Gabriela Ilie, Erin Keltie, Jong Sung Kim Journal: Frontiers in Public Health, Sec. Environmental Health and Exposome Abstract: Introduction: Chronic exposure to arsenic through drinking water has been linked to several cancers. The metabolism of arsenic is thought to play a key role in arsenic-related carcinogenesis as metabolites of varying toxicity are produced and either stored in or excreted from the body. Atlantic Canada has the highest age-standardized incidence rates of all cancers in the country. This may be due to its high levels of environmental arsenic and the prevalence of unregulated private wells for water consumption. Here, we aimed to characterize the profiles of arsenic species and metallome in the toenails of four cancer groups, compare them to healthy participants (N = 338), and assess potential associations between the profiles with cancer prevalence. Methods: This study employed a case–control design. Toenail samples and questionnaire data from cases (breast, cervical, prostate, and skin cancers) and controls were sourced from the Atlantic Partnership for Tomorrow’s Health (PATH) cohort study. The levels of arsenic species were measured using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) paired with High Performance Liquid Chromatography (HPLC) and total concentrations of metallome (23 metals) were determined by ICP-MS separately. Multivariate analyses were conducted to compare cases with controls within each cancer group. Results: Arsenic speciation profiles varied by cancer type and were significantly different between cases and controls in the breast (p = 0.0330), cervical (p = 0.0228), and skin (p = 0.0228) cancer groups. In addition, the profiles of metallome (nine metals) were significantly differentiated in the prostate (p = 0.0244) and skin (p = 0.0321) cancer groups, with higher zinc concentrations among cases compared to controls. Conclusion: History of cancer diagnosis was associated with specific profiles of arsenic species and metallome. Our results indicate that arsenic methylation and zinc levels, as measured in toenails, may be an important biomarker for cancer prevalence. Further research is needed to use toenails as a prognostic measure of arsenic-and other metal-induced cancer. doi: https://doi.org/10.3389/fpubh.2023.1148283

Investigating the Oral Microbiome in Retrospective and Prospective Cases of Prostate, Colon and Breast Cancer

Authors: Jacob Nearing, Vanessa DeClercq, Morgan Langille Journal: Nature Biofilms and Microbiomes Abstract: The human microbiome has been proposed as a potentially useful biomarker for several cancers. To examine this, we made use of salivary samples from the Atlantic Partnership for Tomorrow’s Health (PATH) project and Alberta’s Tomorrow Project (ATP). Sample selection was divided into both a retrospective and prospective case control design examining prostate, breast, and colon cancer. In total 89 retrospective and 260 prospective cancer cases were matched to non-cancer controls and saliva samples were sequenced using 16S rRNA gene sequencing. We found no significant differences in alpha diversity. All beta diversity measures were insignificant except for unweighted UniFrac profiles in retrospective breast cancer cases and weighted UniFrac, Bray-Curtis and Robust Atchinson’s distances in colon cancer after testing with age and sex adjusted MiRKAT models. Differential abundance (DA) analysis showed several taxa that were associated with previous cancer in all three groupings. Only one genus (Clostridia UCG-014) in breast cancer and one ASV (Fusobacterium periodonticum) in colon cancer was identified by more than one DA tool. In prospective cases three ASVs were associated with colon cancer, one ASV with breast cancer, and one ASV with prostate cancer. Random Forest classification showed low levels of signal in both study designs in breast and prostate cancer. Contrastingly, colon cancer did show signal in our retrospective analysis (AUC: 0.737) and in one of two prospective cohorts (AUC: 0.717). Our results indicate that it is unlikely that reliable microbial oral biomarkers for breast and prostate cancer exist. However, further research into the oral microbiome and colon cancer could be fruitful. doi: https://www.nature.com/articles/s41522-023-00391-7

Applying Machine Learning to Arsenic Species and Metallomics Profiles of Toenails to Evaluate Associations of Environmental Arsenic with Incident Cancer Cases

Authors: Sheida Majouni, Jong Sung Kim, Ellen Sweeney, Erin Keltie, Syed Sibte Raza Abidi Ebook: Volume 294: Challenges of Trustable AI and Added-Value on Health Abstract: Chronic exposure to environmental arsenic has been linked to a number of human diseases affecting multiple organ systems, including cancer. The greatest concern for chronic exposure to arsenic is contaminated groundwater used for drinking as it is the main contributor to the amount of arsenic present in the body. An estimated 40% of households in Nova Scotia (Canada) use water from private wells, and there is a concern that exposure to arsenic may be linked to/associated with cancer. In this preliminary study, we are aiming to gain insights into the association of environmental metal’s pathogenicity and carcinogenicity with prostate cancer. We use toenails as a novel biomarker for capturing long-term exposure to arsenic, and have performed toxicological analysis to generate data about differential profiles of arsenic species and the metallome (entirety of metals) for both healthy and individuals with a history cancer. We have applied feature selection and machine learning algorithms to arsenic species and metallomics profiles of toenails to investigate the complex association between environmental arsenic (as a carcinogen) and prostate cancer. We present machine learning based models to ultimately predict the association of environmental arsenic exposure in cancer cases. doi: https://ebooks.iospress.nl/doi/10.3233/SHTI220385

Harnessing the Power of Data Linkage to Enrich the Cancer Research Ecosystem in Canada

Authors: Robin Urquhart, Philip Awadalla, Parveen Bhatti, Trevor JB Dummer, Simon Gravel, Jennifer Vena, Riaz Alvi, Phillipe Broet, Cynthia Kendell, Victoria Kirsh, Guillaume Lettre, Kimberly Skead, Grace Shen-Tu, Ellen Sweeney, Donna Turner Journal: International Journal of Population Data Science Abstract: Objectives: We will enrich the cancer research ecosystem in Canada through linking cancer registry and administrative health data to the Canadian Partnership for Tomorrow’s Health (CanPath) cohort and biobank. CanPath is Canada’s largest population health study, including 1% of the Canadian population, which seeks to investigate cancer development. Approach: We are achieving record-level linkage of the CanPath harmonized dataset to provincial cancer registry data, and hospitalization and ambulatory care data from the Canadian Institutes of Health Information (CIHI). The CanPath harmonized dataset includes comprehensive genetics, environment, lifestyle, and behaviour data. Our linkage activities will result in interprovincial data sharing, with centrally-held linked data, a first in Canadian history. We will demonstrate the CanPath-cancer registry-CIHI linkage potential by investigating the impact of the COVID-19 pandemic on healthcare utilization and outcomes among those with cancer. Results: The linkage is ongoing and anticipated to be completed by September 2022. Linked data will be made available through the CanPath Data Safe Haven, a cloud-based solution that meets the legal requirements of the data sharing agreements and provincial privacy policies, and is accessible to researchers through secure access. The CanPath Data Safe Haven will be a federated data platform for Canadian researchers to access, analyze, and contribute research in a collaborative environment. By linking these datasets, this project will: address concerns related to accessibility of cancer data in Canada; bring more value to existing data; support an enhanced understanding of the impacts of cancer on marginalized populations; and create a more integrated approach to cancer data access and management. Conclusion: CanPath will be the first program in Canadian history to combine the wealth of cohort resources with cancer registry and administrative health data in a central location at a national scale. We will provide a single point of access for researchers to conduct novel investigations into cancer development and outcomes. doi: 10.23889/ijpds.v7i3.1950

Arsenic Speciation and Metallomics Profiling of Human Toenails as a Biomarker to Assess Prostate Cancer Cases: Atlantic PATH Cohort Study

Authors: Erin Keltie, Kalli Hood, Yunsong Cui, Ellen Sweeney, Gabriela Ilie, Anil Adisesh, Trevor Dummer, Veni Bharti, Jong Sung Kim Journal: Frontiers in Public Health (Environmental Health and Exposome) Abstract: Chronic exposure to inorganic arsenic and trace metals has been linked to prostate cancer, and altered arsenic methylation capacity may have an important role in arsenic carcinogenesis. Biomarkers may be able to elucidate this role. Our objectives were to characterize profiles of arsenic species and metallome in toenails and urine samples, compare profiles between prostate cancer cases and controls, and determine the discriminant ability of toenail and urine biomarkers. Toenail samples (n = 576), urine samples (n = 152), and questionnaire data were sourced from the Atlantic Partnership for Tomorrow’s Health (PATH) cohort study. Healthy controls were matched to prostate cancer cases (3:1 ratio) on sex, age, smoking status, and the province of residence. Metallome profiles and proportions of arsenic species were measured in toenail and urine samples. Analysis of covariance (ANCOVA) was used to compare the mean percent monomethylarsonic acid (%MMA), dimethylarsonic acid (%DMA), inorganic arsenic (%iAs), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). Multivariate analysis of covariance (MANCOVA) was used to compare selected metal concentrations. Mean %MMA was significantly lower and SMI was significantly higher in toenails from prostate cancer cases compared to controls in unadjusted and adjusted models. Proportions of arsenic species were correlated with total arsenic in toenails. Arsenic speciation in urine was not different between cases and controls, nor were metallome profiles in toenails and urine. Our results indicate that toenails are a viable biomarker for altered arsenic speciation in prostate cancer cases and may have greater utility than urine in this context.   doi: https://doi.org/10.3389/fpubh.2022.818069

Substituting bouts of sedentary behavior with physical activity: Adopting positive lifestyle choices in people with a history of cancer

Authors: Lee Ingle, Samantha Ruilova, Yunsong Cui, Vanessa DeClercq, Ellen Sweeney, Zhijie Michael Yu, Cynthia C. Forbes Journal: Cancer Causes and Control Abstract Purpose To determine in people with a history of cancer, whether substituting sitting time with other daily activities (i.e., sleeping, walking, moderate and vigorous physical activity) was associated with changes in waist circumference (WC), an important surrogate marker of cardiometabolic risk. Methods Cross-sectional analyses from the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort was conducted using isotemporal substitution models to explore the associations of substituting sedentary time, physical activity behavior (International Physical Activity Questionnaire), or sleep (Pittsburgh Sleep Quality Index) with changes in WC. Analyses were conducted using sex-specific WC classifications. Results In 3,684 people with a history of cancer [mean age (SD) 58.2 (7.3) years; BMI 28.9 (5.2) kg m−2; 71% female], reallocating 10 min of sleep or sedentary time for 10 min of walking was associated with lower WC in women (p < 0.01). In men, PA intensity appeared to be more strongly associated with a reduced WC. Replacing 10 min of sedentary time with 10 min of moderate or vigorous PA and replacing 10 min of sleep with moderate PA were associated with a significantly reduced WC (p < 0.001). The largest effect was when 10 min of moderate PA was replaced with vigorous PA, a reduction in WC (p < 0.01) was evident. Conclusion For people with a history of cancer, adopting small but positive changes in lifestyle behaviors could help reduce WC and potentially offset negative health-related outcomes associated with higher WC. Further research is required to examine whether such an intervention may be acceptable and manageable among this population.   Link: https://link.springer.com/article/10.1007/s10552-022-01592-9

Lifestyle factors and lung cancer risk among never smokers in the Canadian Partnership for Tomorrow’s Health (CanPath)

Journal: Cancer Causes and Control Authors: Rachel A. Murphy,  Maryam Darvishian, Jia Qi, Yixian Chen, Quincy Chu, Jennifer Vena, Trevor J. B. Dummer, Nhu Le, Ellen Sweeney, Vanessa DeClercq, Scott A. Grandy, Melanie R. Keats, Yunsong Cui, Philip Awadalla, Darren R. Brenner & Parveen Bhatti   Abstract Background Although smoking is the primary risk factor for lung cancer, 15–25% of lung cancers occur in never smokers. Emerging evidence suggests lifestyle factors are associated with lung cancer risk, but few studies among never smokers exist. Methods A case–control study of never smokers within the Canadian Partnership for Tomorrow’s Health was conducted. At recruitment, participants provided data on lifestyle, health history and sociodemographic factors. Incident lung cancers were identified through linkage with administrative health records. Cases (n = 190) were matched to controls (n = 760) on age, sex, and follow-up time. Logistic regression analyses, adjusted for matching factors and annual income, were used to identify associations between lifestyle factors and lung cancer risk. Results Consumption of < 5 servings of fruits and vegetables/day was associated with higher risk of lung cancer (OR  1.50, 95% CI 1.03–2.17). Short or long sleep (≤ 6 or > 9 h/night) was also associated with increased risk of lung cancer (OR 1.52, 95% CI 1.01–2.29). No associations were observed for obesity measures, alcohol consumption, or physical activity. Conclusion Our findings provide evidence of a potential role between sleep, fruits and vegetable consumption, and lung cancer risk in a pan-Canadian, non-smoking population. However, the sample size is modest, and further investigation is needed. Doi: https://doi.org/10.1007/s10552-022-01566-x

Investigation of the impact of commonly used medications on the oral microbiome of individuals living without major chronic conditions

Authors: Vanessa DeClercq, Jacob T. Nearing, and Morgan G.I. Langille Journal: PLOS One Abstract Background: Commonly used medications produce changes in the gut microbiota, however, the impact of these medications on the composition of the oral microbiota is understudied. Methods: Saliva samples were obtained from 846 females and 368 males aged 35-69 years from a Canadian population cohort, the Atlantic Partnership for Tomorrow’s Health (PATH). Samples were analyzed by 16S rRNA gene sequencing and differences in microbial community compositions between nonusers, single-, and multi-drug users as well as the 3 most commonly used medications (thyroid hormones, statins, and proton pump inhibitors (PPI)) were examined. Results: Twenty-six percent of participants were taking 1 medication and 21% were reported taking 2 or more medications. Alpha diversity indices of Shannon diversity, Evenness, Richness, and Faith’s phylogenetic diversity were similar among groups, likewise beta diversity as measured by Bray-Curtis dissimilarity (R2 = 0.0029, P = 0.053) and weighted UniFrac distances (R2 = 0.0028, P = 0.161) were non-significant although close to our alpha value threshold (P = 0.05). After controlling for covariates (sex, age, BMI), six genera (Saprospiraceae uncultured, Bacillus, Johnsonella, Actinobacillus, Stenotrophomonas, and Mycoplasma) were significantly different from non-medication users. Thyroid hormones, HMG-CoA reductase inhibitors (statins) and PPI were the most reported medications. Shannon diversity differed significantly among those taking no medication and those taking only thyroid hormones, however, there were no significant difference in other measures of alpha- or beta diversity with single thyroid hormone, statin, or PPI use. Compared to participants taking no medications, the relative abundance of eight genera differed significantly in participants taking thyroid hormones, six genera differed in participants taking statins, and no significant differences were observed with participants taking PPI. Conclusion: The results from this study show negligible effect of commonly used medications on microbial diversity and small differences in the relative abundance of specific taxa, suggesting a minimal influence of commonly used medication on the salivary microbiome of individuals living without major chronic conditions. Doi 10.1371/journal.pone.0261032

Analysis of human serum and urine for tentative identification of potentially carcinogenic pesticide-associated N-nitroso compounds using high-resolution mass spectrometry

Journal: Environmental Research Authors: Crystal L. Sweeney, Nathan K. Smith, Ellen Sweeney, Alejandro M. Cohen, and Jong Sung Kim Abstract: Human serum and urine samples were analyzed for a suite of nitrosatable pesticides and potentially carcinogenic pesticide-associated N–nitroso (PANN) compounds. Formation of PANN compounds may occur in vivo after consumption of food or water containing trace amounts of nitrosatable pesticide residues and nitrate. Using a modified version of the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method, nine nitrosatable pesticides and byproducts were extracted from serum and urine from 64 individuals from two different sample populations in Atlantic Canada: (i) Prince Edward Island, a region where nitrate and trace amounts of nitrosatable pesticides have been detected in groundwater; and (ii) Halifax, Nova Scotia, a non-agricultural urban area. Samples were then analyzed using ultra-high pressure liquid chromatography (UHPLC) coupled with high-resolution accurate mass (HRAM) single-stage orbitrap mass spectrometry (MS), which allows for semi-targeted analysis and tentative identification of a virtually limitless number of exposure biomarkers. Two nitrosatable target analytes, ethylenethiourea (ETU) and 3,5,6-trichloro-2-pyridinol (TCPy) were found in serum, while atrazine (ATR) and ETU were detected in urine. Five and six PANN compounds were tentatively identified in serum and urine, respectively. The two PANN compounds that were most frequently tentatively identified in serum were N-nitroso dimethoate (N-DIM) and N-nitroso omethoate (N-OME) with a detection frequency of 78% and 95%, respectively. This is the first biomonitoring study of its kind to investigate PANN compounds in human serum and urine. https://doi.org/10.1016/j.envres.2021.112493

The Impact of Reporting Magnetic Resonance Imaging Incidental Findings in the Canadian Alliance for Healthy Hearts and Minds Cohort

Journal: BMC Medical Ethics Authors: Judy M. Luu, Anand K. Sergeant, Sonia S. Anand, Dipika Desai, Karleen Schulze, Bartha M. Knoppers, Ma’n H. Zawati, Eric E. Smith, Alan R. Moody, Sandra E. Black, Eric Larose, Francois Marcotte, Erika Kleiderman, Jean-Claude Tardif, Douglas S. Lee, Matthias G. Friedrich on behalf of the CAHHM Study Investigators Abstract Background In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. Methods Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. Results Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. Conclusion The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.   Link: https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-021-00706-3#group-1