GSPT1 and Lung Cancer

The association between GSPT1 and lung cancer represents an emerging area of investigation. Multi‑patient studies have included GSPT1 in gene panels evaluating susceptibility to lung cancer, suggesting that its role in translation termination may intersect with oncogenic processes linked to smoking‐induced malignancy (PMID:8389669). Although the reported studies primarily focused on other candidate genes, GSPT1 was recurrently analyzed alongside well‐established genes in lung cancer, contributing to a broader genetic risk landscape.

Genetic evidence for GSPT1’s role in lung cancer derives from case–control analyses in which germline polymorphisms were investigated. In one study involving 237 cases and 250 controls (PMID:29412865), GSPT1 was among several genes assessed, albeit no specific variant was uniquely isolated for GSPT1. In this context, the variant spectrum remains largely undefined, and no detailed segregation data across families has been provided. Consequently, the genetic evidence is supportive but minimal, making it difficult to delineate a robust pathogenic variant in GSPT1.

The mode of inheritance implied by these studies is suggestive of an autosomal dominant predisposition for lung cancer. Although lung cancer is a complex trait with multifactorial influences, the germline data hint at dominant effects in modifying cancer risk through perturbations in the translational machinery. However, the lack of extensive familial segregation or replication across independent cohorts underscores the preliminary nature of the findings.

Functional studies offer additional insight into the biological plausibility of a disease mechanism involving GSPT1. Multiple experimental investigations have established that GSPT1 interacts with eRF1 in processes critical for translation termination (PMID:12354098; PMID:9712840). These data indicate that disruptions in GSPT1 may affect protein synthesis fidelity and cellular stress responses, pathways that could contribute to oncogenesis. Nonetheless, these mechanistic studies were not performed in a lung cancer context, and their direct relevance to the disease remains to be fully elucidated.

In summary, the association between GSPT1 and lung cancer is supported by limited genetic evidence in multi‑patient studies and bolstered by moderate functional data that demonstrate the gene’s critical role in translation termination. While current studies provide a conceptual link between dysregulated translational control and lung cancer susceptibility, further replication, detailed variant characterization, and segregation analyses are necessary to establish clinical validity.

Key Take‑home: Despite promising mechanistic insights, the current evidence supporting a role for GSPT1 in lung cancer remains limited and requires additional study to inform diagnostic decision‑making and clinical management.

References

• Carcinogenesis • 1993 • Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer PMID:8389669
• Mutation Research. Genetic toxicology and environmental mutagenesis • 2018 • Interactive potential of genetic polymorphism in Xenobiotic metabolising and DNA repair genes for predicting lung cancer predisposition and overall survival in North Indians PMID:29412865
• Genes to cells : devoted to molecular & cellular mechanisms • 2002 • Mouse GSPT2, but not GSPT1, can substitute for yeast eRF3 in vivo PMID:12354098
• The Journal of biological chemistry • 1998 • Molecular cloning of a novel member of the eukaryotic polypeptide chain-releasing factors (eRF) and its interaction with eRF1 PMID:9712840

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