Association Mapping of Genes Using Whole Genome Polymorphism Arrays: Identification of Markers of Breast Cancer Susceptibility in Alberta Women

Breast cancer is a heterogeneous, polygenic disease and is influenced by genetic, environmental and life-style factors. Many single nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified in genome-wide association studies (GWASs) by several research groups for different populations. However, the variants identified so far contribute to a small proportion of disease risk. The objectives of the work described in this thesis were (i) to seek relevance/replicability of reported risk alleles from SNP scans to our study population; and (ii) to perform an independent GWAS for identification of additional/novel polymorphisms in the Albertan population. We approached these two end points by using cases and controls recruited in Alberta (total sample size, n=3064) in a two-stage association study (discovery study followed by replication study). We reproduced 14 of the 28 variants reported by others and also identified seven novel variants associated with breast cancer risk in our study population.