A new study from Washington University School of Medicine reveals how inherited cancer mutations can significantly impact tumor growth and predispose individuals to cancer throughout their lives.

The research analyzed the genomes of over 1,000 cancer patients across 10 cancer types, focusing on inherited mutations, or germline variants, that lead to malfunctioning proteins and impaired physiological functions.

Published in the journal Cell on April 14, 2025, the study emphasizes the need to understand the roles of germline variants in cancer development compared to acquired mutations.

This research enhances understanding of genetic factors that increase cancer risk and could improve future polygenic risk score accuracy.

A polygenic risk score was calculated for each patient to estimate combined cancer risk based on multiple mutations, revealing that those with high scores had more aggressive cancers.

Using precision peptidomics, the study mapped over 330,000 protein-coding germline variants and their effects on protein structure and function in cancer cells.

The researchers identified 119 rare cancer-causing genetic variants and additional common variants that may impact the structure and stability of cancer-related proteins.

Co-corresponding author Dr. Zeynep H. Gümüş emphasizes that inherited genetic variants actively influence tumor formation, evolution, and treatment response.

The team aims to apply their findings to improve cancer immunotherapy outcomes and develop risk prediction models for lung cancer based on inherited genetic profiles.

Senior author Li Ding highlighted the importance of understanding how both common and rare inherited variants affect the body's protein machinery and cancer risk.

Current cancer treatments focus primarily on tumor genetics, but this study suggests that incorporating inherited DNA analysis could enhance diagnosis and treatment selection.

The research supports the idea of personalized cancer care that considers both tumor mutations and the patient's genetic background, though it is based on a primarily European-ancestry cohort.