Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcin

Association Between Early Life Exposure to Phthalates and Organophosphate Esters and the Development of Childhood Asthma and Wheeze

Asthma is the most common chronic disease among children. Children spend most of their early life indoors, exposed to chemicals used in consumer and building products, which may present a risk to asthma development, including phthalates, used as plasticizers, and organophosphate esters (OPEs), used as flame retardants and plasticizers. Few epidemiological studies have examined early life exposure to these chemicals and the development of childhood asthma, as well as the interplay with genetics, which was examined by this dissertation using data from the Canadian CHILD Cohort Study. Using urine samples from 1,578 children collected across early life and 726 house dust samples collected at 3-4 months, I found that Canadian children have ubiquitous early life exposure to phthalates and OPEs. I found higher phthalate metabolite concentrations among children in lower income families. OPE concentrations were higher in dust collected here compared to other studies, possibly due to sampling of the child’s sleeping environment that contains sources of OPEs and phthalates. Using a case-cohort study, I examined the association between early life exposure to phthalates and OPEs, measured in house dust samples collected at 3-4 months, and the development of asthma at 5 years and recurrent wheeze between 2 to 5 years. I found a four-fold increased risk of asthma associated with the highest concentration quartile of di(2-ethyl-hexyl) phthalate (DEHP) and a two-fold increased risk of recurrent wheeze across all quartiles of DEHP compared to the lowest quartile. For OPEs, I observed a two to four-fold increased risk of asthma diagnosis across quartiles of tris(2-butoxyethyl) phosphate exposure compared to the lowest quartile. Using a Genetic Risk Score (GRS) combining multiple genetic loci, I examined whether genetics modifies the association between early life phthalate exposure and the risk of childhood asthma and recurrent wheeze. The GRS did not modify the association with childhood asthma or recurrent wheeze. These results highlight the need to reduce exposure to phthalates and OPEs during early life, especially the first year of life, and the importance of exposures among low-income populations and within the sleeping microenvironment.Ph.D

Fungal colonization of the invasive vine Vincetoxicum rossicum and native plants

Background and aims – Vincetoxicum rossicum (Kleopow) Barbar., an aggressive European plant invader found in Eastern North America, has properties that enable it to establish large monocultures over time, displacing native species and their associated fauna. It has been proposed that V. rossicum also establishes associations with a subgroup of arbuscular mycorrhizal fungi (AMF) that are generalists described as having high infectivity and are particularly efficient with regard to phosphorus uptake. Such associations may also enhance seedling recruitment in mechanically disrupted areas due to the ability of these AMF to colonize roots directly via hyphal fragments as well as via direct spore germination. As well, invasive plants are also suggested to be fungal generalists, providing advantages when establishing in novel environments where fungi may be different from those in their native range. Materials and methods – In a laboratory study we used molecular techniques to investigate the fungal associations of V. rossicum and local native plants goldenrod ( Solidago spp.), wild ginger ( Asarum canadense ), and Canada anemone ( Anemone canadensis ) growing in dense patches of V. rossicum . Key results – The findings indicate that V. rossicum forms associations with a broad array of fungal partners relative to proximal native plants, suggesting the likelihood of it being a fungal generalist. As well, V. rossicum was found to associate with a subgroup of described opportunistic AMF such as Glomus intraradices, G. caledonium, G. fasciculatum and Glomus mosseae, while natives growing within V. rossicum patches were not. Conclusion – Our results suggest that V. rossicum is a fungal generalist, a trait that is beneficial in establishment and persistence. It is useful to understand the fungal association dynamics of V. rossicum when attempting to restore invaded sites, as inoculation with fungal species that are particularly beneficial to the establishment of V. rossicum may be avoided

Fungal colonization of the invasive vine Vincetoxicum rossicum and native plants

Background and aims – Vincetoxicum rossicum (Kleopow) Barbar., an aggressive European plant invader found in Eastern North America, has properties that enable it to establish large monocultures over time, displacing native species and their associated fauna. It has been proposed that V. rossicum also establishes associations with a subgroup of arbuscular mycorrhizal fungi (AMF) that are generalists described as having high infectivity and are particularly efficient with regard to phosphorus uptake. Such associations may also enhance seedling recruitment in mechanically disrupted areas due to the ability of these AMF to colonize roots directly via hyphal fragments as well as via direct spore germination. As well, invasive plants are also suggested to be fungal generalists, providing advantages when establishing in novel environments where fungi may be different from those in their native range. Materials and methods – In a laboratory study we used molecular techniques to investigate the fungal associations of V. rossicum and local native plants goldenrod ( Solidago spp.), wild ginger ( Asarum canadense ), and Canada anemone ( Anemone canadensis ) growing in dense patches of V. rossicum . Key results – The findings indicate that V. rossicum forms associations with a broad array of fungal partners relative to proximal native plants, suggesting the likelihood of it being a fungal generalist. As well, V. rossicum was found to associate with a subgroup of described opportunistic AMF such as Glomus intraradices, G. caledonium, G. fasciculatum and Glomus mosseae, while natives growing within V. rossicum patches were not. Conclusion – Our results suggest that V. rossicum is a fungal generalist, a trait that is beneficial in establishment and persistence. It is useful to understand the fungal association dynamics of V. rossicum when attempting to restore invaded sites, as inoculation with fungal species that are particularly beneficial to the establishment of V. rossicum may be avoided

Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcinoma had the strongest association with cumulative radon exposure; compared to the reference group (<1 cumulative working level months (WLM)), the highest exposure category (>60 cumulative WLM) had a relative risk (RR) of 2.76 (95% CI: 1.67⁻4.57). Adenocarcinoma had the lowest risk and was not significantly associated with exposure to radon decay products (RR = 1.49, 95% CI: 0.96⁻2.31). An increasing, linear trend in relative risk was noted with increasing cumulative WLM across small cell, squamous cell, and large cell lung carcinomas (Ptrend < 0.05). Similarly, the excess relative risk (ERR) per WLM was highest for small cell lung carcinoma (ERR/WLM = 0.15, p < 0.01), followed by squamous cell carcinoma (ERR/WLM = 0.12, p < 0.01). Non-statistically significant excess risk was observed for adenocarcinoma (ERR/WLM = 0.004, p = 0.07). Our analysis of the Ontario Uranium Miners cohort data shows differences in the magnitude of the risks across four histological subtypes of lung carcinoma; the strongest association was noted for small cell lung carcinoma, followed by squamous cell, large cell, and lastly adenocarcinoma, which showed no significant associations with exposure to radon decay products

Cancer incidence and mortality from exposure to radon progeny among Ontario uranium miners

Objectives The study objectives were to extend the follow-up of the Ontario uranium miners cohort, one of the largest cohorts of uranium miners with low cumulative exposures, to examine the relationship between radon exposure and lung cancer mortality and, for the first time incidence, and address gaps in the literature, including dose-response relationship between radon exposure and other cancer sites, and non-cancer mortality. Methods The cohort of mine and mill workers was created using data from Canada's National Dose Registry and the Ontario Mining Master File. The follow-up for the cohort was recently extended for mortality (1954- 2007) and for the first time includes cancer incidence (1969-2005). The Poisson regression was used to estimate relative risks (RR) and excess relative risks (ERR) and their 95% CIs with levels of cumulative radon exposure. Results The cohort consisted of 28 546 male miners with a mean cumulative radon exposure of 21.0 working level months (WLM). An increased risk of lung cancer and a dose-response relationship was observed with cumulative radon exposure. Miners exposed to >100 WLM demonstrated a twofold increase in the risk of lung cancer incidence (RR=1.89, CI 1.43 to 2.50) compared with the non-exposed group, and a linear ERR of 0.64/ 100 WLM (CI 0.43 to 0.85), with similar results observed for mortality. No association was observed for other cancer sites (stomach, leukaemia, kidney and extrathoracic airways) or non-cancer sites (cardiovascular diseases) with increasing cumulative exposure to radon. Conclusions These findings suggest no increased risk of cancer sites other than lung or non-cancer mortality from relatively low cumulative exposure to radon