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Full NameDr Nick Orr
Department:Centre for Cancer Research and Cell Biology
Organisation:Queen's University Belfast
- genetics, genomics and molecular biology
- epidemiology/population health research
Over the past 10 years my group has focused on cancer genetic epidemiology and the functional genomic mechanisms that underpin cancer predisposition. Much of my team’s focus has been on susceptibility to breast cancer, with recent emphasis on male breast cancer and radiation induced breast cancer. Current goals are to i) characterise germline susceptibility to breast cancer using functional genetic analysis, ii) define the genomic and histological landscape of male breast tumours, iii) develop blood-based biomarkers for early detection of breast and ovarian cancer and iv) characterise genetic predisposition factors and molecular pathology of radiation induced breast cancer.
Inherited predisposition to breast cancer is mediated via germline mutations and polymorphisms that vary in effect size and population allele frequency. Rare, but highly penetrant, mutations in genes such as BRCA1 and BRCA2 are well established risk factors for the disease. More recently, a large number of common single nucleotide polymorphisms that individually confer small increases in risk have been detected using genome-wide association studies. However, a large proportion of the excess familial risk of breast cancer remains undetected and it is likely that at least some will be explained by low frequency polymorphisms that confer modestly increased risks of the disease. Although the advent of next generation sequencing has enabled high-throughput ascertainment of rare variants in putative predisposition genes, a major challenge has been in differentiating those that are “causal” from those that are not. This project aims to use functional genetic approaches to analyse putative rare breast cancer predisposing variants identified in a recent high throughput sequencing study of male breast cancer, in order to increase our understanding of genetic susceptibility to both female and male breast cancer.