Open Collections

Occupational exposure to polycyclic aromatic hydrocarbons, breast cancer risk, and interactions with genetic variants

University of British Columbia

Polycyclic aromatic hydrocarbons (PAHs) are created by the incomplete combustion of fossil fuels, and are established human carcinogens. However, the effect of occupational PAH exposure on breast cancer is not well established. In addition, it is not known if genes involved in metabolizing xenobiotic compounds modify the risk of breast cancer in women exposed to PAHs. The objectives of this study were to (1) estimate the association between PAH exposure and breast cancer, (2) examine how variants of select xenobiotic metabolizing genes influence breast cancer risk, and (3) assess how these variants – several of which are involved in PAH metabolism – interact with PAH exposure to modify breast cancer risk. The relationships between PAH exposure, genetic susceptibility, and breast cancer were examined in a population-based case control study conducted in Vancouver, BC and Kingston, Ontario. A detailed questionnaire, including occupational history, and biological sample were collected from participants. Chapter 2 details how I developed a statistical model that predicts the probability of exceeding the permissible exposure limit for PAH through industry and occupation using workplace compliance testing data collected in the United States. Chapter 3 describes the use of the model to develop a job exposure matrix and estimate the association between PAH exposure and breast cancer. In Chapter 4, I assessed the associations between select gene variants and breast cancer, and evaluated whether there is evidence that those variants modify PAH exposure effect on breast cancer risk. Long term exposure to PAHs was identified as a risk factor for breast cancer, and risk was highest among premenopausal women and women with a first degree family history of breast cancer. Six variants in xenobiotic metabolizing genes were observed to be related to breast cancer risk, three of which are directly involved in PAH metabolism. In addition, there is evidence to support the notion that three of these variants modify the effect of PAH exposure, implicating the role gene-environment interactions have on modifying breast cancer risk. Evidence from this research points to the potential importance of monitoring and limiting occupational exposures to PAHs in order to reduce breast cancer risk in women.

Text

2017-01-21

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/60291

Population and Public Health

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/