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A protocol for using human genetic data to identify circulating protein level changes that are the causal consequence
Lisa M Hobson1,2, Richard M Martin2,3, Karl Smith-Byrne3,4
1MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Plos One
|December 5, 2025
Summary
This study identifies protein changes linked to genetic risk for lung and colorectal cancers. These findings could aid in developing new early detection and screening methods for these common diseases.
Area of Science:
- Genomics
- Proteomics
- Cancer Research
Background:
- Cancer is a major global health challenge, with early detection significantly improving patient outcomes.
- Identifying circulating protein biomarkers offers a promising avenue for minimally invasive cancer screening and risk stratification.
- Current challenges remain in detecting cancer at its earliest stages.
Purpose of the Study:
- To identify protein level changes associated with genetic liability for lung and colorectal cancers.
- To explore potential protein biomarkers for early cancer detection and risk stratification.
- To distinguish causal relationships between protein changes and cancer genetic liability.
Main Methods:
- Utilized the PRS-CS and PRS-CSx methods to calculate polygenic risk scores (PRS) for colorectal and lung cancer risk.
- Assessed the association between PRS and 2923 proteins using linear regression in UK Biobank participants.
- Employed Mendelian randomization and colocalization analyses to investigate causal relationships and potential biases.
Main Results:
- Identified specific protein level changes associated with genetic predisposition to lung and colorectal cancers.
- The study explored the temporal relationship between protein measurements and cancer diagnosis.
- Results pave the way for understanding molecular events preceding or following cancer onset.
Conclusions:
- Protein changes downstream of genetic liability may serve as crucial indicators for cancer risk and early detection.
- Further research can leverage these identified proteins for developing novel diagnostic strategies.
- This work contributes to advancing precision oncology through biomarker discovery.
