TRANSGENERATIONAL CARCINOGENESIS: RISK FACTORS AND EPIGENETIC MECHANISMS (A LITERATURE REVIEW)

Abstract

Introduction: Traditional models of carcinogenesis based on genetic mutations and direct exposure to carcinogens cannot explain all cases of cancer. The increasing incidence of certain cancers does not always correlate with known genetic factors, suggesting a significant role for environmental and lifestyle factors in their development. The concept of transgenerational carcinogenesis offers a new explanation, linking these factors with an increased risk of cancer in future generations through epigenetic changes. 

This study aimed to systematize and critically analyze scientific publications published between 2014 and 2024 that concern the factors contributing to transgenerational carcinogenesis and the underlying epigenetic mechanisms. 

Methods: To identify relevant publications, extensive searches were conducted in electronic databases, including PubMed/ MEDLINE, Scopus, and Web of Science. Combinations of keywords were used: (“transgenerational” OR “intergenerational” OR “parental exposure”) AND (“cancer” OR “carcinogenesis” OR “tumor” OR “oncogenesis”) AND (“epigenetic” OR “DNA methylation” OR “histone modification” OR “miRNA” OR “non-coding RNA”). 

Results: The phenomenon of transgenerational carcinogenesis, which is the transmission of an increased risk of cancer from generation to generation, is a proven fact. Epigenetic changes that persist in the germline affect gene expression in subsequent generations, and can be caused by various factors affecting the parents. Animal models provide convincing evidence of cause-and-effect relationships. Long-term cohort studies in humans consistently confirm this mechanism, despite methodological difficulties. 

Conclusion: Epigenetic changes in the germline can be passed on to offspring, significantly increasing their risk of developing pathological neoplasms. The primary mediators are changes in DNA methylation, histone modifications, and modifications to non-coding RNA. The study of transgenerational carcinogenesis will allow for the prevention of malignant neoplasms in future generations. Cause-and-effect relationships are convincing in models; in human populations, evidence is limited by associations and requires multigenerational cohorts with admixture control.