Project Details

04/06/2026

Targeted exposure assessment to study the role of environmental chemicals on the development of breast cancer among Iranian women

Restricted Access - Data is not openly available and can only be accessed under specific agreements or conditions

Breast cancer is the most prevalent malignancy and the primary cause of cancer-related mortality among women worldwide. According to the International Agency for Research on Cancer (IARC) report (2022), Iran records approximately 15,000 new female breast cancer cases annually, and this number is projected to increase by about 47% by 2050. Despite well-established genetic and hormonal risk factors, the rising incidence of breast cancer underscores the need to identify additional modifiable determinants. Growing evidence suggests that exposure to environmental pollutants, including heavy metals and persistent organic pollutants (POPs), among others, may contribute to the development or progression of breast carcinogenesis. A major challenge, however, is the complexity of real-world exposure patterns, which typically involve mixtures rather than single exposures. Nevertheless, many epidemiologic studies have predominantly evaluated individual pollutants, whereas integrated assessment of combined exposures has received limited attention. Moreover, substantial gaps remain in elucidating the cellular and molecular mechanisms linking chemical exposures to breast cancer development. Gut microbiota has been proposed as a potential mediator linking environmental exposures to breast cancer. The intestinal microbiota, known as the “second genome,” represents one of the most complex and dynamic microbial ecosystems within the human body, comprising trillions of bacteria, viruses, fungi, and protozoa. This microbial consortium plays a profound and multifaceted role in host health by participating in the regulation of a broad spectrum of biochemical and physiological processes. Nevertheless, gut microbiota dysbiosis has been strongly associated with the onset and progression of numerous diseases, including neurodegenerative disorders, cardiovascular events, diabetes, and cancer. In particular, the gut microbiome has emerged as a key contributor to breast carcinogenesis. Recent studies suggest that alterations in its composition and function can influence breast cancer initiation, metastasis, and treatment response through multiple mechanisms, including immune modulation, estrogen metabolism, metabolic homeostasis, and direct genotoxic effects. Conversely, exposure to various chemical pollutants can induce gut microbial imbalance, potentially activating inflammatory, hormonal, and metabolic pathways and thereby increasing the risk of breast cancer. However, the contribution of microbial dysbiosis to breast carcinogenesis associated with environmental exposures has been largely overlooked. This issue is more pronounced in countries with a high environmental pollution burden, including Iran, where environmental contamination constitutes a major public health challenge. Across the country, large urban and industrial areas experience recurrent episodes of degraded air quality, resulting in chronic exposure to elevated levels of particulate matter (PM₂.₅ and PM₁₀) and gaseous pollutants (e.g., NO₂/NOx, SO₂, and CO). Beyond inhalation pathways, multi-compartment contamination may sustain long-term exposure through drinking-water pollutants (e.g., nitrate and arsenic), incomplete removal of persistent and emerging contaminants in conventional wastewater treatment, and widespread soil contamination from industrial and agricultural chemicals (including heavy metals and pesticides) and inadequate municipal waste management, with subsequent transfer into the food chain. Collectively, these mixture exposures may increase internal dose to potentially carcinogenic compounds and elevate the risk of malignancies, underscoring the need for integrative, combined-exposure assessment in this setting. This study thus aims to investigate the associations among exposure to chemical pollutants, gut microbiota alterations, and breast cancer risk. To address this objective, a matched case–control study has been designed. Specifically, the study will: (1) quantify the association between combined exposure to selected chemicals and breast cancer risk; (2) characterize gut microbiota diversity and composition in breast cancer cases compared with matched controls; and (3) evaluate whether gut microbiota alterations mediate the associations between chemical exposures and breast cancer risk, thereby providing deeper insight into potential underlying biological mechanisms. The study will enroll approximately 200 breast cancer cases and 200 controls, matched on age (±5 years), residential address, and menopausal status. Participants will be women aged 18–65 years recruited from the Cancer Institute, Tehran University of Medical Sciences, and classified as cases or controls according to predefined study criteria. Biological samples (hair, stool, and blood) will be collected from all participants. Exposure to chemical pollutants will be assessed by quantifying their concentrations in hair samples using validated analytical methods (LC–MS/MS, GC–MS, and MP-AES). Gut microbiota profiles will be characterized in stool samples using 16S rRNA gene sequencing. The findings of this study are expected to provide novel insights into the functional pathways linking environmental exposures to mammary tumorigenesis and to inform the development of innovative approaches for breast cancer prevention and early detection. Moreover, the results may contribute to establishing a conceptual framework to advance precision therapeutic strategies for breast cancer treatment.