Air Pollution and Breast Cancer: An Examination of Modification By Underlying Familial Breast Cancer Risk

Background: An increased familial risk of breast cancer may be due to both shared genetics and environment. Women with a breast cancer family history may have a higher prevalence of breast cancer-related gene variants and thus increased susceptibility to environmental exposures. We evaluated whether air pollutant and breast cancer associations varied by familial risk.

Methods: Sister Study participants living in the contiguous United States at enrollment (2003-2009; N = 48,453), all of whom had at least one first-degree relative with breast cancer, were followed for breast cancer. Annual NO₂ and PM_2.5 concentrations were estimated at the enrollment addresses. We predicted 1-year familial breast cancer risk using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). Using Cox regression, we estimated HRs and 95% confidence intervals (CI) for associations between each pollutant dichotomized at the median and breast cancer with interaction terms to examine modification by BOADICEA score.

Results: NO₂ was associated with a higher breast cancer risk among those with BOADICEA score >90th percentile (HR, 1.28; 95% CI, 1.05-1.56) but not among those with BOADICEA score ≤90th percentile (HR, 0.98; 95% CI, 0.90-1.06; P _interaction = 0.01). In contrast to NO₂, associations between PM_2.5 and breast cancer did not vary between individuals with BOADICEA score >90th percentile and ≤90th percentile (P _interaction = 0.26).

Conclusions: Our results provide additional evidence that air pollution may be implicated in breast cancer, particularly among women with a higher familial risk.

Impact: Women at higher underlying breast cancer risk may benefit more from interventions to reduce exposure to NO₂.