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

NCT07631624 | Recruiting DMC

• 1 other identifier: 4607
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

DNA-methylation; Lung Cancer Screening; Risk stratification; Smoking; Saliva

Outcome Measures

Primary Outcomes (1)

• DNA-methylation

  DNA Methylation Status, measured as a continuous variable across a panel of specific genes (e.g., AHRR, F2RL3, ALPPL2).

  3 years

Secondary Outcomes (1)

• Comparative smoking accuracy

  2 years

Study Arms (2)

Cohort - volunteers

EXPERIMENTAL

Reference group: people who smoked less than 10 years

Genetic: DNA-methylation in saliva

Cohort: Lung cancer screening participants

EXPERIMENTAL

Participants of the ZORALCS-study

Genetic: DNA-methylation in saliva

Interventions

DNA-methylation in saliva GENETIC

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.

Cohort - volunteers; Cohort: Lung cancer screening participants

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Must be \> 50 years of age
• Smoking History: Includes individuals with and without a smoking history
• Cohort 2: ZORALCS-study participants
• Age: 55-74 years old
• Smoking History: Includes individuals with a smoking history

Sponsors & Collaborators

• Universiteit Antwerpen: collaborator
• University Hospital, Antwerp: lead

Study Sites (1)

Antwerp University Hospital

Antwerp, Antwerpen, 2650, Belgium

RECRUITING

MeSH Terms

Conditions

Smoking

Interventions

DNA Methylation

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena

Study Officials

• Annemiek Snoeckx, MD, PhD

  University Of Antwerp / Antwerp University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlotte Theuns

CONTACT

+32470274088; charlotte.theuns@uantwerpen.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: June 8, 2026
• Study Start: October 4, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: June 8, 2026

Record last verified: 2026-04

Locations

BE (1)