The Impact of Community Social Capital on the occurrence of Injuries in adolescents and falls in older adults: Population-based Studies Conducted in Canadian samples

The objectives of this thesis were to study specific Canadian populations in order to examine; (1) relationships between the neighbourhood-level social capital and injuries in youth, as well as (2) falls in older adults, and; (3) to address methodological issues relevant to the study of such relationships. The thesis is comprised of four manuscripts. The first addresses methodological issues surrounding the validation of neighbourhood-level variables for the study of adolescent health, and demonstrates the existence of structural confounding in the study of related etiological relationships. Informed by the latter, the second manuscript examines the association between neighbourhood-level social capital and injuries in youth, and demonstrates that lower levels of social capital are protective factors for girls but not for boys. Manuscript 3 uses an international database focused on older adults, and shows that our existing measure of social capital is valid at neighbourhood levels, but also that there is a high possibility for the existence of structural confounding among Canadian older adults. The fourth manuscript then examines the association between neighbourhood-level social capital and the occurrence of falls in older adults and determines that differences between neighbourhoods are important factors in the occurrence of falls, and that higher levels of social capital are a risk factor for falls. Taken together, results from this thesis provide a better understanding of the role of neighbourhood-level social capital on the occurrence of injuries in Canadian youth and on the occurrence of falls in older adults. Our contributions were important both methodologically and etiologically.

Genetic Polymorphisms in Replication-related Genes and Risk of Breast Cancer Among European and East Asian Women

Background: The role of common, low to intermediate risk alleles in breast cancer need to be examined due to their relatively high prevalence. Among many cellular pathways, replication has a pivotal role in cell division and frequently targeted during carcinogenesis. Replication is governed by a host of genes involved in a number of different pathways. This study investigates the effects of replication-gene variants in relation to breast cancer and how this relationship is affected by ethnicity, menopausal status and breast tumour subtype. Methods: Data from a case-control study with 997 incident breast cancer cases and 1,050 age frequency matched controls in Vancouver, British Columbia and Kingston, Ontario were used. Unconditional logistic regression was used to calculate odds ratios between 45 replication gene variants and breast cancer risk, assuming an additive genetic model adjusted for age and centre, presented for Europeans and East Asians separately. Polytomous logistic regression was used to assess odds ratios between each SNP and four breast cancer subtypes defined by hormone receptor status among Europeans. All analyses were stratified by menopausal status. The Benjamini–Hochberg false discovery rate (FDR) was used to address multiple comparisons. Results: Among Europeans, the SNPs in FGFR2, TOX3 and 11q13 loci were associated with breast cancer after controlling for multiple comparisons. Test of heterogeneity showed the SNPs rs1045185, rs4973768, rs672888, rs1219648, rs2420946 among Europeans and rs889312 among East Asians conferred differential risk across the tumour subtypes. Conclusions: Specific SNPs in replication genes were associated with breast cancer, and the risk level differed by tumour subtype defined by ER/PR/Her2 status and ethnicity.