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

Five Years of Team PATH and Plaid for Dad

The Atlantic PATH team is always happy to support the Canadian Cancer Society’s Plaid for Dad event which raises awareness about prostate cancer and supports prostate cancer research in Canada. There were two years when we could be together for Plaid for Dad in the office and with our office dog Flash. We’re happy to be able to continue participating while we work from home during COVID-19 the past few years, safely social distancing! You can read more about the Plaid for Dad campaign here: https://bit.ly/3QrMbZC                            

Congratulations to Dr. Robin Urquhart and the CanPath team across the country!

Funded by the Canadian Cancer Society Data Transformation Grant, this work will connect cancer registry and administrative health data with CanPath data creating a unified resource for cancer research in Canada. https://bit.ly/3OojlZ2 Urquhart R, Awadalla P, Bhatti P, Dummer T, Gravel S, Vena J, Alvi R, Broet P, Kendell C, Kirsh V, Lettre G, Skead K, Sweeney E, Turner D. Harnessing the power of linked data to understand cancer and its outcomes: a national linkage project. March 2022-March 2023, CCS Data Transformation Grant. Canada has a wealth of health care and health research data, but numerous barriers prevent efficient sharing of these datasets between provinces. This, combined with further difficulties with linking datasets together, causes major limitations in using the data productively to improve the health of Canadians. With support from the Canadian Cancer Society, Dr Urquhart will lead a team to connect several cancer registry and administrative health data repositories, creating a unified resource for cancer research in Canada. One of the datasets, CanPath, contains data on 1 in 100 Canadians, including lifestyle, family histories, genetics and environment and this, combined with other datasets, will be analysed to understand the causes of cancer and what happens to people with cancer in the short- and long-term. The researchers will also be able to ask important questions about the impact of the COVID-19 pandemic on people who have been diagnosed with cancer during this time. Linking these huge datasets will provide a very important resource for cancer research in Canada.

Congratulations to Drs. Syed Sibte Raza Abidi, Jong Sung Kim, Ellen Sweeney, Gabriela Ilie, and Trevor Dummer on a successful New Frontiers in Research Fund’s Exploration grant.

The highly competitive funding is meant to support high-risk, high-reward and interdisciplinary research. The NFRF funding is “especially meaningful because it encourages our scholars to push the boundaries of knowledge. This is how great discoveries are made,” says Alice Aiken, Vice-President, Research and Innovation. “It’s exciting to see our researchers harnessing machine learning, natural language processing and other cutting-edge techniques to reveal new truths that can improve our health and society.” (Source: DalNews, https://bit.ly/3O8Agi7). Using Atlantic PATH data and toenail samples, this funding will allow the research team to expand on their work on arsenic-related cancer and machine learning. Based on Canada’s geology, arsenic represents one of the most prevalent environmental carcinogens linked to skin, bladder, kidney, prostate, lung, breast, and cervical cancer. Half of Canadians are susceptible to develop cancer in their lifetime, with risk modified heavily by genetic susceptibility, behavioural factors and environmental exposure. While cancer risk prevention strategies have extensively focused on physiological and behavioural factors, environmental exposure as a cancer risk has not been well studied which has led to missed opportunities to reduce the risk of cancer through environmental population health programs, such as reducing chronic arsenic exposure by treating contaminated groundwater currently consumed by Canadians. Increased arsenic levels in human toenails have been detected in the Atlantic PATH cohort. Innovative population health interventions, focusing on predicting the susceptibility and type of arsenic induced cancer across Canada are urgently needed to mitigate the increasing prevalence of cancers in Canada. This work will investigate environmental cancer biomarkers and develop innovative data-driven environmental cancer risk assessment tools to help reduce the incidence of cancers caused by arsenic exposure. Please stay tuned for updates from this project!

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

Participant Town Hall

Did you miss CanPath’s Participant Town Hall? It can be viewed on CanPath’s YouTube channel. Learn about how participant data and biosamples are being used in cancer, COVID-19 and chronic disease research. English: https://www.youtube.com/watch?v=UbBFTVwKOzE French: https://www.youtube.com/watch?v=Yj7tfI_ay04

New Publication! Toenail speciation biomarkers in arsenic‐related disease: a feasibility study for investigating the association between arsenic exposure and chronic disease

Congratulations to Nathan Smith & colleagues!! Based on his MSc research, this is important foundational work examining toenails as biomarkers for arsenic speciation that Atlantic PATH and the HERC Lab continue to build on. https://bit.ly/332UU0r

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