INVESTIGATIONAL REVIEW OF GENETICS CANCER OUTCOMES BY DNA REFLECTION IN PEOPLE WITH AND WITHOUT GENETIC CANCER GENES GENETICALLY
DOI:
https://doi.org/10.71000/j2xn6j32Keywords:
Germline Genetics, ; Cancer Outcomes, Hereditary Cancer Syndromes, Variants of Uncertain Significance, Polygenic Risk Score, Precision Oncology.Abstract
Background: The role of germline genetics in cancer is rapidly evolving beyond risk assessment. While pathogenic variants in high-penetrance genes are established risk factors, their influence on therapeutic response and long-term outcomes, alongside the enigmatic roles of variants of uncertain significance (VUS) and polygenic risk, is a critical area of investigation. This narrative review explores the expanding impact of the germline genome on cancer care.
Objective: This review aims to synthesize current evidence on how germline genetic factors, both established and potential, influence cancer outcomes, comparing trajectories between individuals with and without identified hereditary cancer syndromes.
Main Discussion Points: Key themes include the validated prognostic and predictive utility of high-penetrance genes like BRCA and DNA mismatch repair genes in guiding targeted therapy. The discussion also encompasses the clinical challenges posed by VUS, the emerging potential of polygenic risk scores, and the profound impact of germline genetics on somatic evolution and clonal selection. Significant methodological limitations and the lack of diversity in genomic research are critically analyzed as major constraints within the existing literature.
Conclusion: Evidence strongly supports integrating germline testing into oncology to guide treatment for specific syndromes. However, the broader application of genetics for prognostication requires further validation. Future efforts must prioritize inclusive, large-scale prospective studies to translate the full potential of germline information into equitable, personalized cancer care.`
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Copyright (c) 2025 Irfan Ishaque, Duaa Sheeraz Samoo, Muhammad Sohaib Hassan, Mariam Kamran, Safia Ghulam Rasool, Abbas Ali, Arshad Aziz (Author)
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