Derrick G Lee1,2, Johanna M Schuetz3, Agnes S Lai4, Igor Burstyn5, Angela Brooks-Wilson3,6, Kristan J Aronson7,8,9, John J Spinelli10. 1. Cancer Control Research, BC Cancer, Vancouver, BC, Canada. dlee@stfx.ca. 2. Department of Mathematics and Statistics, St. Francis Xavier University, Antigonish, NS, Canada. dlee@stfx.ca. 3. Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada. 4. Cancer Control Research, BC Cancer, Vancouver, BC, Canada. 5. Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA. 6. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada. 7. Department of Public Health Sciences, Queen's University, Kingston, ON, Canada. 8. School of Environmental Studies, Queen's University, Kingston, ON, Canada. 9. Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Kingston, ON, Canada. 10. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
Abstract
PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutants associated with multiple cancers, including female breast cancer. Several xenobiotic metabolism genes (XMGs), including the CYP450 family, play an important role in activating and detoxifying PAHs, and variations in the activity of the enzymes they encode can impact this process. This study aims to examine the association between XMGs and breast cancer, and to assess whether these variants modify the effects of PAH exposure on breast cancer risk. METHODS: In a case-control study in Vancouver, British Columbia, and Kingston, Ontario, 1037 breast cancer cases and 1046 controls had DNA extracted from blood or saliva and genotyped for 138 single nucleotide polymorphisms (SNPs) and tagSNPs in 27 candidate XMGs. Occupational PAH exposure was assessed using a measurement-based job-exposure matrix. RESULTS: An association between genetic variants and breast cancer was observed among six XMGs, including increased risk among the minor allele carriers of AKR1C3 variant rs12387 (OR 2.71, 95% CI 1.42-5.19) and AKR1C4 variant rs381267 (OR 2.50, 95% CI 1.23-5.07). Heterogeneous effects of occupational PAH exposure were observed among carriers of AKR1C3/4 variants, as well as the PTGS2 variant rs5275. CONCLUSION: Our findings support an association between SNPs of XMGs and female breast cancer, including novel genetic variants that modify the toxicity of PAH exposure. These results highlight the interplay between genetic and environmental factors, which can be helpful in understanding the modifiable risks of breast cancer and its complex etiology.
PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutants associated with multiple cancers, including female breast cancer. Several xenobiotic metabolism genes (XMGs), including the CYP450 family, play an important role in activating and detoxifying PAHs, and variations in the activity of the enzymes they encode can impact this process. This study aims to examine the association between XMGs and breast cancer, and to assess whether these variants modify the effects of PAH exposure on breast cancer risk. METHODS: In a case-control study in Vancouver, British Columbia, and Kingston, Ontario, 1037 breast cancer cases and 1046 controls had DNA extracted from blood or saliva and genotyped for 138 single nucleotide polymorphisms (SNPs) and tagSNPs in 27 candidate XMGs. Occupational PAH exposure was assessed using a measurement-based job-exposure matrix. RESULTS: An association between genetic variants and breast cancer was observed among six XMGs, including increased risk among the minor allele carriers of AKR1C3 variant rs12387 (OR 2.71, 95% CI 1.42-5.19) and AKR1C4 variant rs381267 (OR 2.50, 95% CI 1.23-5.07). Heterogeneous effects of occupational PAH exposure were observed among carriers of AKR1C3/4 variants, as well as the PTGS2 variant rs5275. CONCLUSION: Our findings support an association between SNPs of XMGs and female breast cancer, including novel genetic variants that modify the toxicity of PAH exposure. These results highlight the interplay between genetic and environmental factors, which can be helpful in understanding the modifiable risks of breast cancer and its complex etiology.
Authors: Derrick G Lee; Igor Burstyn; Agnes S Lai; Anne Grundy; Melissa C Friesen; Kristan J Aronson; John J Spinelli Journal: Occup Environ Med Date: 2019-01 Impact factor: 4.948