Environmental Exposures during Puberty: Window of Breast Cancer Risk and Epigenetic Damage

Abstract

During puberty, a woman's breasts are vulnerable to environmental damage ("window of vulnerability"). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures.

Keywords: breast cancer risk; empowerment; environment.

Figure 1

(A) Stages of breast development. The breast is unique in that full maturation of the breast does not occur until later in life, after puberty. During puberty, the female breast undergoes rapid changes: proliferating terminal end buds and elongation of the ducts promote the formation of primitive lobular structures and growth of the ductal tree. Breast development illustrations courtesy of the University of California Davis School of Medicine, Robert Cardiff MD, PhD, and Hannah Jensen MD (open source information) [15]. (B) The high-risk field hypothesis is that specific genetic or epigenetic alterations may occur in a breast progenitor cell prior to, or during puberty, and the clonal expansion of a damaged progenitor during puberty would result in a localized predisposed terminal ductal lobular unit (TDLU) or “high-risk” field, from which breast cancer subsequently would arise. A second genetic or epigenetic “hit” in a high-risk field is hypothesized to survive and propagate with a higher frequency than a similar “hit” in a normal breast lobule.

Figure 2

Epigenetic modifications of chromatin structure. Chromosomes are composed of DNA–protein complexes called chromatin. The basic subunit of chromatin is the nucleosome, which comprises an octamer of two copies of each of the core histone proteins—H2A, H2B, H3, and H4—wrapped by 147 bp of chromosomal DNA. Condensed chromatin is generally characterized by promoter DNA methylation and histone methylation, depending on the site of modification on the histone (for example, lysine 9 methylation (K9Me) and lysine 27 methylation (K27Me) on histone H3), resulting in repressed gene expression. Relaxed chromatin is marked by histone lysine acetylation and methylation of lysine 4 on histone 3 (K4Me) in the promoter regions, that promote gene expression. Histone lysine acetylation at the enhancer region also enhances gene expression by interacting with the promoter region through bromodomain-containing proteins (BRD) and other proteins. RNA methylation is a form of epigenetic regulation related to the translation and degradation of RNAs. Figure adapted from Kato et al. [38].

Figure 3

Young women are bombarded with environmental exposures before and at the time of puberty that include polluted water, contaminated soil, industrial waste, pesticides (in water, food, soil), hair care products, and cosmetics.

Figure 4

Identify, Prevent, Advocate. Here, our team of scientists, teachers, advocates, and state representatives aim to work together to mentor young women to reduce toxic exposures during puberty and promote healthy diets and exercise within their families and communities. IDENTIFY: We will use our established science technology, engineering, and math (STEM) program to allow young women to work with our scientists to measure chemicals in their environment. PREVENT: We will work with community advocates school and environmental state officials to develop ways to avoid toxic exposures. ADVOCATE: We will work with state and national officials to help our young women present their findings to our state legislature and US House of Representatives. In doing so, our team will help mentor young women who are scientifically trained and will provide our next generation of advocates.