Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline

Abstract

The past decade has made evident that in addition to passing their genetic material at conception, parents also transmit a molecular memory of past environmental experiences, including nutritional status, to their progeny through epigenetic mechanisms. In the 1990s, it was proposed that breast cancer originates in utero. Since then, an overwhelming number of studies in human cohorts and animal models have provided support for that hypothesis. It is becoming clear, however, that exposure in the parent generation can lead to multigenerational and transgenerational inheritance of breast cancer. Importantly, recent data from our lab and others show that pre-conception paternal diets reprogram the male germline and modulate breast cancer development in offspring. This review explores the emerging evidence for transgenerational epigenetic inheritance of breast cancer focusing on studies associated with ancestral nutritional factors or related markers such as birth weight. We also explore paternal factors and the epigenetic mechanisms of inheritance through the male germline while also reviewing the existing literature on maternal exposures in pregnancy and its effects on subsequent generations. Finally, we discuss the importance of this mode of inheritance in the context of breast cancer prevention, the challenges, and outstanding research questions in the field.

Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring

“…influence the outcome of BCa through transgenerational epigenetic inheritance (da Cruz et al, 2020). The present study evaluated the influence of maternal diet on BCa development in F1 offspring using BALB/c mice and investigated the associated genome-wide epigenetic and transcriptional changes.…”

“…Recently, Xavier et al (2019) reviewed the impact of various environmental factors, including diets on epigenetic states, and how they can be hereditably transmitted. More precisely, recent evidence has shown that parental diets can influence the outcome of BCa through transgenerational epigenetic inheritance ( da Cruz et al, 2020 ). The present study evaluated the influence of maternal diet on BCa development in F1 offspring using BALB/c mice and investigated the associated genome-wide epigenetic and transcriptional changes.…”

Diagnostic Value of FTO Combined with CEA or CYFRA21-1 in Nonsmall Cell Lung Cancer

“…Epigenetics has become a primary research field over the past several years [7]. According to prior research [8], DNA and histone modification are the focuses in epigenetics.…”

Epigenetic Inheritance: Intergenerational Effects of Pesticides and Other Endocrine Disruptors on Cancer Development

“…Epigenetic patterns are faithfully transmitted between cells during mitotic division, but accumulating evidence suggests that epigenetic information can also be transmitted between generations [17,18]. Accordingly, studies suggest that the progeny's health phenotypes can be acquired in an epigenetically inherited manner due to parental environmental exposures [18,19]. This environmentally induced disease risk has been shown to be transmitted to the offspring via epigenetic mechanisms through both the female and male germ-lines [20][21][22].…”

“…Ongoing mouse studies in our lab show that preconception paternal exposure to DDT increases mammary tumorigenesis and tumor aggressiveness in female offspring. The offspring's phenotype is linked to alterations in the sperm small non-coding RNA load of males exposed to DDT [19].…”