Breast Cancer Risk - Environmental and Genetic Effects on Cancer Development, Progression and Survival

Abstract

Breast cancer is a common, complex multifactorial disease which has an estimated risk in the UK of 1 in 9 women. Due to its prevalence there has been a great deal of research carried out to identify risk and prognostic factors which are involved in its pathogenesis. By reviewing this vast array of literature conclusions have been drawn as to which factors are consistently associated with risk and prognosis. These include high penetrance genetic factors such as BRCA1, BRCA1, PTEN; and low penetrance mutations including FGFR2, CASP8 and ESR1. Additionally environmental factors influence risk, including reproductive factors, alcohol consumption, smoking and social deprivation. Of the factors identified in this literature review there was evidence that there may be common biological mechanisms underlying their role in breast cancer risk. For example, oestrogen signalling pathways and DNA repair pathways were commonly proposed as the mechanism underlying both genetic and environmental risk.
To demonstrate the impact of environmental risk factors on breast cancer outcome a survival analysis was carried out on 1851 women diagnosed with primary breast cancer between 2000 and 2004. Using SPSS to analyse the data it was found that women from the most deprived areas in Tayside had the poorest breast cancer outcome – these outcomes included all-cause mortality, breast cancer specific death and breast cancer recurrence. When the analysis was adjusted for staging information the significant difference in breast cancer specific 5 year survival was lost. Therefore this suggests that deprived women
present with higher stage tumours, which is one of the reasons underlying their poorer outcome.
This thesis clarifies the risk and prognostic factors associated with breast cancer, and demonstrated that in a Tayside cohort deprivation is associated with poor outcome. In addition common biological mechanisms have been identified as associated with these risk factors. It is only through thinking of breast cancer in a holistic manner and incorporating different aspects of breast cancer pathogenesis a better understanding of the disease can be gained, and new risk factors identified. By understanding this better it is hoped that this will lead to improved preventative measures and the development of more targeted treatment options.

Date of Award	2015
Original language	English
Awarding Institution	University of Dundee
Supervisor	Jonathan Berg (Supervisor)