Explore the profound implications of how childhood cancer shapes the human gene pool, shedding light on our evolutionary resilience and challenges.
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The evolutionary impact of childhood cancer on the human gene pool.
Stoltze et al., Nat Commun 2024
<!– DOI: 10.1038/s41467-024-45975-9 //–>
https://doi.org/10.1038/s41467-024-45975-9
This study delves into the impact of natural selection on germline pathogenic variants linked to increased childhood mortality, particularly focusing on pediatric cancer predisposition syndrome (pCPS) genes. Analyzing genetic data from 4,574 children with cancer and 141,456 adults, the research reveals that pCPS genes are under strong selective pressure, evidenced by harboring only a quarter of the expected loss-of-function variants. This finding is consistent across pediatric and adult cohorts. Interestingly, six genes (ELP1, GPR161, VHL, and SDHA/B/C) showed a lack of mutational constraint, questioning their role in pediatric cancer severity. Conversely, among 23 known biallelic risk pCPS genes, two (DIS3L2 and MSH2) demonstrated significant constraint, suggesting a potential monoallelic increase in childhood cancer risk. This study underscores the power of natural selection in shaping the gene pool concerning heritable childhood cancers, providing empirical evidence of its significant impact.
Importance: Highlights the role of natural selection in reducing the prevalence of harmful genetic variants associated with childhood cancer, offering insights into the genetic landscape of pediatric cancer predisposition.