Methylated Biomarkers of Smoking as a Selection Tool in Participants for Lung Cancer Screening

Summary

The MET-SELS study aims to revolutionize how we identify individuals for lung cancer screening by moving beyond the limitations of self-reported smoking history. Currently, eligibility for low-dose CT (LDCT) scans relies on "pack-years"-a metric often compromised by recall bias, under-reporting, and an inability to account for the biological nuances of smoke inhalation or environmental exposure. Consequently, current criteria miss nearly half of incidental lung cancers.

To bridge this gap, the study investigates DNA methylation as a stable, objective "biological footprint" of smoking. Unlike short-term biomarkers like nicotine or CO levels, specific epigenetic changes in genes such as AHRR and F2RL3 persist long after cessation and correlate accurately with cumulative tobacco exposure.

Led by Professor Dr. Annemiek Snoeckx and a multidisciplinary team at UZA and the Centre for Medical Genetics, the research will analyze saliva samples from two groups: roughly 900 participants from the ZORALCS screening trial and 150 volunteers. By comparing saliva-derived genomic signatures against both self-reported data and professional interviews, the team aims to validate a panel of methylation markers that can pinpoint high-risk individuals with far greater precision.

The ultimate vision for MET-SELS is to implement a population-based "saliva-first" triage system, similar to the FIT test used for colorectal cancer. In this model, high-risk candidates would provide a saliva sample at home; only those with a confirmed epigenetic risk profile would be invited for a LDCT scan, significantly increasing the yield of early-stage lung cancer detection while streamlining healthcare resources.

Conditions

• Epigenetics
• DNA Methylation
• Lung Cancer Screening
• Risk Stratification With Biomarker
• Saliva

Interventions

GENETIC

DNA-methylation in saliva

Participants provide a simple 2 ml saliva sample, which is far less invasive and more cost-effective for mass screening than blood-based liquid biopsies. These samples undergo rigorous genomic and methylomic analysis at the Centre for Medical Genetics, employing techniques such as whole-genome sequencing (WGS) and quantitative methylation-specific PCR (qMSP). These biological results are then cross-referenced against two types of behavioral data: self-reported questionnaires and intensive, structured interviews led by specialized healthcare providers. By using ROC analysis and linear regression, the study aims to validate how accurately these salivary biomarkers can predict smoking status, pack-years, and duration of abstinence compared to traditional reporting.

Sponsors & Collaborators

• Universiteit Antwerpen

  collaborator OTHER

• University Hospital, Antwerp

  lead OTHER

Principal Investigators

• Annemiek Snoeckx, MD, PhD · University Of Antwerp / Antwerp University Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

SCREENING

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-10-04

Primary Completion

2027-01-01

Completion

2028-01-01

Countries

• Belgium

Study Locations