Breast Cancer and Exposure to Organochlorines in the CECILE Study: Associations with Plasma Levels Measured at the Time of Diagnosis and Estimated during Adolescence.

Delphine Bachelet,Corinne Charlier,Sami Haddad,Patrick Arveux,Pascal Guénel,Émilie Cordina Duverger,Marc-André Verner,Monica Neri

doi:10.3390/ijerph16020271

Abstract

Exposure to environmental chemicals with hormonal effects, such as organochlorine compounds (OCs), during developmental periods of breast cells may have an impact on the incidence of breast cancer later in life. However, the assessment of exposure to these chemicals that occurred in early life at the time of breast cancer development in adult women is a difficult challenge in epidemiological studies. Plasma levels of the OCs p,p’-dichlorodiphenyl dichloroethene (DDE) and polychlorinated biphenyl congener 153 (PCB153) were measured in 695 cases and 1055 controls of a population-based case-control study conducted in France (CECILE study). Based on these values, we used a physiologically-based pharmacokinetic (PBPK) model to estimate PCB153 levels at age 11–20 years when the women were adolescents. Overall, there was no clear association between breast cancer risk and measured levels of DDE and PCB153 at the time of diagnosis, but there was a trend of decreasing odds ratios of breast cancer with increasing DDE and PCB153 levels in women aged 50 years and over. The PBPK model revealed that PCB153 concentrations estimated during adolescence were highest in the youngest women born after 1960 who reached adolescence at a time when environmental contamination was maximum, and very low in the oldest women who attained adolescence before the contamination peak. Negative associations between breast cancer and PCB153 estimates during adolescence were also found. The negative associations between DDE and PCB153 levels measured at the time of diagnosis or estimated during adolescence in our study were unexplained. Further investigations are needed to clarify whether this finding is real or related to study artifacts. However, this study suggests that using PBPK models in epidemiological studies to back-estimate OC exposures during early life stages may be useful to address critical questions on cancer development.

Highlights

With approximately 1.7 million new cases each year around the world, breast cancer is the most frequent malignant disease among women [1]
We investigated the association between breast cancer and plasma levels of DDE and polychlorinated biphenyl congener 153 (PCB153) measured at the time of breast cancer diagnosis in a large case-control study conducted in France
Plasma levels of DDE and PCB153 measured at the time of breast cancer diagnosis were not clearly associated with risk in our study, but a negative association between concentration of both

Summary

Introduction

With approximately 1.7 million new cases each year around the world, breast cancer is the most frequent malignant disease among women [1]. Persistent organic pollutants are mostly lipophilic environmental pollutants that tend to accumulate and biomagnify in food chains, resulting in considerable exposure of living organisms. These compounds include polychlorinated biphenyls (PCBs), which were utilized worldwide in numerous industrial and commercial applications, and organochlorine pesticides like dichlorodiphenyltrichloroethane (DDT), which has been used in agriculture and as a pest control agent [4]. Both of these classes of organochlorine compounds (OC) have attracted attention because of their widespread occurrence in the environment and in human beings, and their potential ability to interfere with hormone-regulated processes [5]. The strongest evidence for risk to human health is for dioxin-like PCBs, though they cannot be considered as the only responsible agent of PCB carcinogenicity

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