Longevity-associated FOXO3 genotype mitigates the risk of lung cancer after smoking cessation: a prospective…

Cohort studyTranslational lung cancer research· Jul 2026

Longevity-associated FOXO3 genotype mitigates the risk of lung cancer after smoking cessation: a prospective cohort study.

Randi Chen, Timothy A Donlon, Vanessa L Cunanan … Kamal H Masaki

Public Health & General Preventive MedicineCohort studyPrognosisQ2IF 2.7

FOXO3 longevity-gene carriers have lower lung cancer risk after quitting smoking

Longevity-associated FOXO3 genotype mitigates the risk of lung cancer after smoking cessation: a prospective cohort study.

Randi Chen … Kamal H Masaki

Translational lung cancer research · Jul 2026

Background

Smoking cessation lowers lung cancer (lung cancer) risk, but the magnitude of risk reduction varies across individuals.

Purpose

The aim of the present study was to investigate whether FOXO3 genotype modifies the association between smoking cessation and incident lung cancer.

Methods

Were genotyped for FOXO3 rs2802292 and classified as FOXO3 -G (TG/GG; longevity-associated G-allele carriers) or FOXO3 -TT (TT, common allele homozygotes).

n = 4,339 ever-smoking American men of

Results

Among former smokers, longevity-gene carriers had lower lung cancer risk than non-carriers.

HR 0.42 (95% CI 0.23 to 0.79)

CI excludes the null - significant

More results

During 28 years of follow-up, 180 lung cancer cases occurred, including 117 non-small cell lung cancer (non-small cell lung cancer) cases.

Significant interactions were observed between smoking status and FOXO3 genotype for lung cancer (P=0.02) and non-small cell lung cancer (P=0.003).

More results

In contrast, no genotype-related differences were observed among current smokers.

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Conclusion · 1 of 3

FOXO3 genotype may modify lung cancer risk associated with smoking cessation.

Conclusion · 2 of 3

Compared with carriers of the longevity-associated FOXO3 G allele, individuals with the FOXO3 -TT genotype had a substantially elevated risk of lung cancer after smoking cessation; this association was not observed among current smokers.

Conclusion · 3 of 3

These findings support the potential for genotype-informed precision prevention, pending replication in larger and more diverse cohorts.

Longevity-associated FOXO3 genotype mitigates the risk of lung cancer after smoking cessation: a prospective cohort study.

Longevity-associated FOXO3 genotype mitigates the risk of lung cancer after smoking cessation: a prospective cohort study.

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