The study of cancer genomics has revealed that both inherited (germline) and acquired (somatic) genetic variations significantly influence cancer susceptibility, initiation, and progression. Despite groundbreaking findings from genome-wide association studies (GWAS) and large-scale tumor sequencing projects, the interplay between germline risk loci and somatic mutation landscapes remains incompletely understood. Recent evidence underscores the complexity of cancer’s genetic architecture, implicating noncoding variants, structural rearrangements, and ancestry-specific effects in disease risk and outcomes. Ongoing debates focus on how best to integrate diverse forms of genomic data and translate molecular discoveries into improved risk prediction, early detection, and personalized therapies for cancer patients. While integrative, multi-omic approaches are beginning to shed light on these questions, mechanistic links and actionable insights are still needed across diverse cancer types and patient populations.

This Research Topic aims to advance our understanding of how genomic variation, both inherited and somatic, drives cancer susceptibility and influences disease progression. We seek original research, reviews, and perspectives that: map functions of cancer-associated loci, dissect interactions between germline and somatic alterations, and develop integrative models leveraging bulk and single-cell data. Key objectives include identifying molecular drivers of aggressive disease, elucidating ancestry- and context-specific genetic effects, and revealing biomarkers or pathways that may inform prevention, risk stratification, and therapeutic strategies. Researchers are encouraged to contribute novel statistical, computational, or experimental methods that bridge the gap between molecular genetics and clinical oncology.

This topic covers the spectrum from discovery science to translational research on the genomic determinants of cancer risk and progression. Submissions focusing exclusively on either germline or somatic mutations without considering their interaction, or those outside the context of cancer, will fall outside the primary scope. To gather further insights in this field, we welcome articles addressing, but not limited to, the following themes:

• Integration of germline and somatic variants in cancer risk models
• Functional annotation and experimental validation of cancer-linked genetic loci
• Multi-omics and computational frameworks for predicting disease trajectories
• Genomic determinants of metastasis, relapse, and therapy response
• The role of population diversity and ancestry in cancer genomics
• Liquid biopsy and single-cell approaches for tracking clonal evolution
• Translational applications for biomarker and therapeutic target identification

Are you interested in contributing a manuscript to this Research Topic?

Genomic Insights Into Cancer Susceptibility and Progression