![]() ![]() This review explores the evidence for epigenetic inheritance of breast cancer focusing on studies associated with ancestral nutritional factors or related markers such as birth weight. However, recent findings from our lab and others argue for a contribution of paternal pre-conception exposures to offspring's breast cancer risk in rodent models. ![]() In line with that, it was proposed that some breast cancers may originate in utero ( 20) when the mammary tissue first arises and multiple reports on maternal exposure in pregnancy have offered support to that hypothesis ( 4, 21– 23). It has been suggested that inconsistencies between certain environmental factors and breast cancer are due to timing of exposure and windows of susceptibility at different stages of mammary gland development throughout a women's lifetime ( 18, 19). Exceptions include alcohol consumption, obesity, and inadequate physical activity, which are strongly associated with breast cancer ( 15– 17). Although a number of nutritional and lifestyle factors have been linked with breast cancer, these associations are mostly inconsistent ( 14). The majority of breast cancers are sporadic and thought to result from environmental and lifestyle exposures ( 13). This suggests that the familial or inheritable component of some breast cancers is not only transmitted by classical genetic inheritance but could also be mediated through non-genetic mechanisms. Despite intense search, no major genetic mutations have emerged ( 12). However, mutations in high penetrance genes such as BRCA1 and BRCA2 explain only a small proportion of breast cancers. Although most of the evidence for this mode of disease inheritance comes from maternal exposures in pregnancy, we ( 6, 7) and others ( 8– 10) have shown that paternal exposures in the pre-conception window are also important in determining disease outcomes in the offspring.įamily history is an important risk factor for breast cancer and it accounts for up to one third of all cases ( 11). Indeed, environmentally induced disease risk has been experimentally shown to be transmitted from one generation to another via epigenetic mechanisms both through the female and male germlines ( 2, 4, 5). ![]() ![]() While DNA sequence is responsible for the majority of heritability of disease, including cancer, it is becoming clear that epigenetic inheritance can also occur. Because epigenetic plasticity peaks in early development, the risk of diseases such as breast cancer can result from environmental exposures acting in that life stage ( 2, 3). The genome is relatively stable throughout an organism's life span however, the epigenome is malleable to ensure short-term adaptation to the environment ( 1). 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. 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. 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. 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. It is becoming clear, however, that exposure in the parent generation can lead to multigenerational and transgenerational inheritance of breast cancer. Since then, an overwhelming number of studies in human cohorts and animal models have provided support for that hypothesis. In the 1990s, it was proposed that breast cancer originates in utero. 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.
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