Association between long-term ambient air pollution exposure and the risk of breast cancer: a systematic review and meta-analysis.

Breast cancer is a complex and multifactorial disease which stems significantly from both environmental and genetic factors. A growing number of epidemiological studies have suggested that ambient air pollution (AAP) exposure may play an important role in breast cancer development. However, no consistency has been reached concerning whether high levels of air pollutant exposure were related to increased breast cancer risk among the current evidence. To further clarify such association of long-term AAP exposure with risk of breast cancer, a systematic review and meta-analysis of available evidence was performed. An extensive literature search in 3 academic databases was conducted before March 10, 2020. The risk of bias (RoB) for each individual study was evaluated with a domain-based assessment tool, developed by the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT). Meta-estimates for air pollutant-breast cancer combinations were calculated for a standardized increment in exposure by random-effect models. The confidence level in the body of evidence and the certainty of evidence was also assessed for each air pollutant-breast cancer combination. The initial search identified 5446 studies, and 18 of them were eligible. The pooled analysis found an increased risk of breast cancer was associated with an increase in each 10 μg/m in nitrogen dioxide (NO) exposure (hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01, 1.04), while particulate matter with aerodynamic diameters ≤ 2.5 μm and 10 μm (PM, PM) revealed no statistically significant associations with breast cancer risk. Our evaluation on the certainty of evidence indicates that there was a "moderate level of evidence" in the body of evidence for an association of NO exposure with an increased breast cancer risk and an "inadequate level of evidence" in the body of evidence for an association of PM and PM exposure with an increased breast cancer risk. Our study suggests long-term exposure to NO is related to an increased risk of breast cancer. However, in consideration of the limitations, further studies, especially performed in developing countries, with improvements in exposure assessment, outcome ascertainment, and confounder adjustment, are needed to draw a definite evidence of a causal relationship.