Breast cancer has the highest incidence of cancer among women in Taiwan, and the rate is increasing year by year.^[1] On the basis of statistics from the National Health Insurance Research Databases (NHIRD), the incidence and mortality of breast cancer has grown to 69.1 and 12.0 per 100,000 population, respectively.^[1]

Many clinical studies have revealed that cancer is related closely to ambient particulate matters (PMs), where the air pollution is a ubiquitous and complex mixture of pollutants.^[2] PM of diameter up to 10 μm (PM₁₀) and fine PM, up to 2.5 μm (PM_2.5), are known as a significant risk factor for human health status.^[3] Outdoor air pollution and airborne PM were considered as the group 1 of carcinogen for humans by the International Agency for Research on Cancer.^[4] An American study suggests that exposure to high levels of PM may have injurious effects on the length of survival to breast cancer, particularly among women who were diagnosed with early stage cancers.^[5] Furthermore, a Japanese study found that PM_2.5 levels estimated from the measured PM₁₀ levels has significant association with the mortality of breast, endometrial, and ovarian cancers.^[6] However, there is currently no relevant data and research conducted in Taiwan to discuss the relevance of PM_2.5 to breast cancer. Thus, we investigated the correlation of breast cancer with common air pollutants by using a nationwide, population-based database in Taiwan.

A total of 98,011 patients with CO concentration data, 98,017 patients with NO and NO₂ concentration data, 96,643 patients with PM_2.5 concentration data, and 74,016 patients with THC and CH4 concentration data were analyzed. The sociodemographic factors and urbanization level of patients with CO, NO, NO₂, PM_2.5, THC and CH₄ are demonstrated in Tables 1–6.

Table 1 shows the baseline characteristics of participants exposed to 4 levels of CO concentration. There were more patients that lived in the highest CO concentration areas (27.4%). Compared with the other CO concentration stratification, those exposed to the Quartile 1 level of CO concentration were the oldest. The distributions of monthly incomes and urbanization levels were similar. Patients living in the highest urbanization areas were exposed to the highest CO concentration (53.9%), and patients who lived in the highest CO concentration had the most people diagnosis breast cancer (1.47%).

Table 2 presents the baseline characteristics of participants exposed to 4 levels of NO concentration. The patients who were exposed the Quartile 1 level of NO concentration were also the oldest. The distributions of monthly incomes and urbanization levels were also similar. Patients who lived in the highest urbanization areas and monthly income is 14,400 to 18,300 were dominant. Patients who lived in the highest NO concentration also had the most people diagnosed with breast cancer (1.41%).

In Table 3, there were more patients living in the Quartile 3 level of NO₂ concentration areas (30.1%) compared to other Quartile levels. The patients who were exposed to the Quartile 1 level of NO₂ concentration were the oldest, while those exposed to the Quartile 3 level of NO₂ concentration were the youngest. Most patients living in the highest NO₂ concentration areas also lived in areas of high urbanization and have monthly incomes between 14,400 and 18,300. Patients who lived in the highest NO concentration also had the most people diagnosis breast cancer (1.63%).

There were more patients living in the lowest level of PM_2.5 concentration areas (29.1%) in Table 4. Patients who were exposed to the Quartile 4 level of PM_2.5 concentration were the oldest, and those exposed to the Quartile 2 level of PM_2.5 concentration were the youngest. Patients who lived in the highest PM_2.5 concentration area also had the highest level of breast cancer diagnosis (0.91%). Although the higher the PM_2.5 concentration in statistics, the higher the diagnosis of breast cancer, but there is no statistically significant difference in the P value (P value = .36). I think PM_2.5 may cause a higher risk of breast cancer, but it will not increase as the concentration of PM_2.5 increases.

Tables 5 and 6 demonstrates the distributions of age, monthly income, and urbanization levels in THC and CH4 data. The distributions of monthly incomes and urbanization levels were similar between gas concentration stratification in THC and CH4 data. Patients who lived in the highest THC concentration and CH₄ concentration also had the most people diagnosis breast cancer (1.53% and 2.33%, respectively).

Table 7 presents the associations between pollutant levels and the risk of breast cancer. The adjusted hazard ratios of breast cancer after exposure to the Quartile 2, Quartile 3, and Quartile 4 levels were compared with those after exposure to the Quartile 1 level. With an interquartile range increase in each pollutant, adjusted HRs were significant. Compared to the lowest quartile of each air pollutant, subjects who were exposed to the highest quartile (Quartile 4) had a significantly higher risk of breast cancer (CO: adjusted HR = 1.85 [95% CI: 1.54–2.21]; NO: adjusted HRs = 1.63 [95% CI: 1.37–1.95]; and NO₂: adjusted HR = 1.79 [95% CI: 1.45–2.15]; PM_2.5: adjusted HRs = 1.29 [95%CI:1.07–1.56]; THC: adjusted HRs = 3.53 [95%CI:2.76–4.50]; CH4: adjusted HRs = 4.95 [95%CI:3.92–6.26]).

In this study, we examined the association between air pollutant levels and risk of adult-onset breast cancer, and showed a significant higher risk in higher pollution level areas. We found that while individual characteristics of the urbanization level consistently associated with increased breast cancer risk, the relationship of NO and PM_2.5 between Q2, Q3 did not show clear correlation.

Previous study suggested that the high incidence rate of female breast cancer in the US was associated with high air pollutants emission regions (NO and CO), which was consistent with our results.^[7] However, 2 previous studies found no obvious association between long-term exposure to air pollution and breast cancer incidence,^[8,9] while 1 found traffic-related childhood exposure was not associated with an increase to breast cancer risk.^[10] Reding et al showed no significant associations between air pollution and breast cancer risk. On the other hand, they found NO₂ was associated with an increased risk of ER+/PR+ breast cancer via their cohort study result.^[11] Garcia et al studied the correlation between an increase of breast cancer risk and several air pollutant compounds, including acrylamide, carbon tetrachloride, chloroprene, 4,4’-methylene bis (2-chloroaniline), propylene oxide, and vinyl chloride, but hazard ratios were not statistically significant.^[12] In addition, 1 reviewing study summarized the results for 8 case-control studies and 9 cohort studies and suggested little evidence to support a relationship between PM and breast cancer risk.^[14] There were also studies that supported our hypothesis. Goldberg et al reported that exposure to ambient NO₂ and UFPs may increase the risk of incident postmenopausal breast cancer, especially women with positive estrogen and progesterone receptor status.^[13] The different outcomes and conclusions can be explained with climate, cultural differences, or population density, but more studies and analysis are needed in order to draw conclusive correlation between air pollution and breast cancer risk in Taiwan.

There are some limitations in this study. First, there are several confounders, such as demographic variables, lifestyle, diet habits, underlying disease, and genetic background that maybe to effect the incidence of breast cancer. Second, we did not analyze which type of breast cancer is highly associated with air pollutants because it is closely related to the prognosis of breast cancer. In this study, we tried to analyze the relationship between pollutants and the risk of breast individually. But in the real world, these pollutants do not exist individually, they always exist with other molecular compounds. In the future, we may consider collecting more information such as living habits, eating habits, past medical history, or genetic factors for further statistical analysis and using SPSS software to do multivariate analysis may make this research more rigorous and precise.

Although the risk factors that increase cancer are numerous and complex, they are often accompanied by more than 1 risk factor. According to research statistics, some air pollutants are closely related to the risk of breast cancer, we are not clear about the time of exposure to air pollution or the mechanism of carcinogenesis. With the progress of urbanization in Taiwan, the effect of environmental air pollution becomes more and more serious, and the incidence rate of cancer in Taiwan is also rising. Ambient air pollution may be an important factor in the increase of breast cancer incidence. Research into environmental chemical exposure helps prevent and promote public health benefits.

Data curation: Yu-Chia Li, Cheng-Li Lin.

Formal analysis: Cheng-Li Lin.

Software: Cheng-Li Lin.

Supervision: James Cheng-Chung Wei, Ming-Hsin Yeh.

Validation: James Cheng-Chung Wei.

Writing – original draft: Yu-Chia Li.

Writing – review & editing: James Cheng-Chung Wei, Ming-Hsin Yeh.