Environmental risks and cancer in unborn children: A transplacental perspective

This is an Honourable Mention of the 2024 Molecular Oncology Writing Competition: Impact of the exposome on cancer risk.
Environmental risks and cancer in unborn children: A transplacental perspective
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As part of World Cancer Day (4th Feb), the journal of Molecular Oncology invited researchers to take part in a writing competition aimed at highlighting the impact of the exposome on cancer risk. This entry, by Patrick Felber (University of Edinburgh, UK), received an Honourable Mention.

Cancer, following accidents, stands as the second primary cause of death in children, with leukaemia and lymphomas being the most prevalent. Infant leukaemia, distinct from its childhood counterpart due to its severity and early onset, alongside other childhood tumours, have raised concerns about prenatal exposures influencing cancer risk. This essay examines how environmental risks can potentially cause cancer in unborn children, focusing on transplacental exposure and its multifaceted impacts.

Transgenerational carcinogenesis

Transgenerational carcinogenesis refers to the transmission of altered genetic and epigenetic information from parents to offspring, potentially leading to cancer development in later generations. This phenomenon is of particular interest when considering environmental exposures that may not cause immediate manifestations in exposed individuals but can have latent effects on their progeny. Such inherited alterations could be the result of mutations, epigenetic modifications, or other heritable changes in the germ line caused by environmental agents. The potential for carcinogens to affect germ cells implies that cancer risk may be predetermined even before conception, underscoring the need for protective measures in populations of reproductive age.

The intricate dance of epigenetics and environment

Environmental epigenetics, a rapidly evolving field, sheds light on how environmental exposures can influence gene expression without altering the underlying DNA sequence. Specific molecules like methyl groups can attach to DNA, acting as a dimmer switch, turning genes on or off. Environmental factors like air pollution, heavy metals, and even diet can influence these epigenetic modifications. These alterations, in turn, can be passed down through generations, potentially increasing the susceptibility of offspring to developing cancer later in life. 

Distinguishing between risks before conception and during pregnancy

Before conception, both prospective parents' exposures to environmental carcinogens can affect the quality of their germ cells, thus setting the stage for potential adverse outcomes in their children. For example, paternal exposure to certain chemicals has been linked to an increased risk of childhood leukemia and other cancers in their offspring. The period before conception is critical for both parents to minimize exposure to known and suspected carcinogens.

During pregnancy, the focus shifts to the mother's exposure, as the fetus develops in utero. Transplacental exposure becomes the primary concern, as the placenta serves as a conduit for both nutrients and potential toxins. The developing fetus is particularly vulnerable during certain windows of susceptibility, where exposure to carcinogens can disrupt normal development and set the stage for cancer and other diseases.

Risk groups of parents: Occupational patterns

Parents' occupational patterns significantly influence the degree of environmental exposure to potential carcinogens. For instance, industries involving the use of chemicals, radiation, or heavy metals pose a higher risk for workers, which may be transferred to their unborn children. Healthcare workers frequently exposed to chemotherapeutic agents or ionizing radiation, agricultural workers handling pesticides, and factory workers dealing with industrial waste are at heightened risk. These occupational risks necessitate targeted interventions, including workplace safety regulations and preconceptional counseling to minimize the transplacental transfer of hazardous substances.

Prenatal basis of childhood cancer

The biological responses to carcinogens from environmental exposure in adults take years to manifest. However, during transplacental exposure, the effects on the fetus evolve rapidly, intertwining with developmental mechanisms. This implies that even brief periods of exposure can have lifelong consequences, leading to childhood cancers.

Air pollution, both outdoors from vehicles and industry and indoors from materials and furniture, poses a direct risk to developing fetuses through transplacental exposure to toxic compounds like PAHs and dioxins.

Pesticides add another layer of risk, with their varied and changing chemical compositions over the years making it difficult to fully understand their long-term effects on transplacental cancer risk.

In addition to air and chemical exposures, food contaminants, particularly acrylamide from improperly cooked foods, are under investigation for their potential role in increasing the risk of cancer in children via transplacental pathways.

Water contaminants also present a significant risk. Arsenic, a carcinogen that can cross the placental barrier, affects millions globally through contaminated drinking water and industrial processes, potentially impacting fetal development.

Finally, ionizing radiation, although less of a concern today due to improved medical practices, has historically been associated with increased cancer risks in children when fetuses are exposed to low doses, especially during the final trimester.

Considering the extended risks of transgenerational carcinogenesis and parental occupational exposures, it becomes evident that cancer prevention strategies must begin well before pregnancy and continue throughout gestation. This expanded perspective calls for a broader scope of public health initiatives, including preconception education about environmental risks, workplace reforms to protect reproductive health, and strengthened regulations to limit exposures to known carcinogens.


Photo by Javier Miranda on Unsplash

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