Dependence of cancer risk from environmental exposures on underlying genetic susceptibility: an illustration with polycyclic aromatic hydrocarbons and breast cancer

Background: Most studies of environmental risk factors and breast cancer are conducted using average risk cohorts. Methods: We examined the association between polycyclic aromatic hydrocarbon (PAH)-albumin adducts in bloods from baseline and breast cancer risk in a prospective nested case-control study (New York site of the BCFR, 80 cases and 156 controls). We estimated the 10-year absolute breast cancer risk by a risk model that uses pedigree information (BOADICEA) and evaluated whether the increased risk from PAH differed by absolute risk. Results: Women with detectable levels of PAH had a twofold association with breast cancer risk (odds ratio (OR)=2.04; 95% CI = 1.06-3.93) relative to women with non-detectable levels. The association increased with higher levels of PAH (Xmedian) and by a higher level of absolute breast cancer risk (10-year risk >= 3.4%: OR = 4.09, 95% CI = 1.38-12.13). Conclusions: These results support that family-based cohorts can be an efficient way to examine gene-environment interactions.