Lung cancer in never-smokers is increasingly recognized as a disease influenced by genetic susceptibility. Aldehyde-metabolizing enzymes, including the ALDH gene family and ADH1B, play key roles in detoxifying reactive aldehydes that can damage DNA and promote oxidative stress. In this study, we will examine whether ten selected genetic variants, nine single nucleotide polymorphisms (SNPs) across five ALDH family genes and one variant in ADH1B are associated with the risk of lung cancer and its major subtypes. Limited epidemiological evidence is currently available on the association between these aldehyde-metabolizing gene variants and lung cancer. This research aims to clarify their potential contribution to the development of lung cancer, particularly among never-smokers.

This case-control study aims to investigate the association of ten genetic variants-nine SNPs across five ALDH family genes and one SNP in ADH1B (rs1229984)-with the risk of lung cancer and its major subtypes. The primary hypothesis is that the ALDH2 rs671 variant is associated with the risk of lung cancer and its major subtypes. The secondary hypothesis is that other ALDH variants-including rs2228093 and rs2073478 in ALDH1B1, rs1127717 and rs2276724 in ALDH1L1, rs3741172, rs17856219, and rs77341916 in ALDH3B2, and rs3765310 in ALDH5A1-are also associated with lung cancer risk. Demographic and lifestyle covariates such as age, gender, ethnicity, smoking status, alcohol consumption, educational level, and case-control status will be incorporated into the analysis.

Inclusion Criteria:

• Incident lung cancer cases confirmed by pathology and healthy adult over age of 18 years.

Exclusion Criteria:

• Individuals with incomplete data will not be included as study participants.

Lung cancer status determined by pathology-confirmed diagnosis at the time of case identification

IPD will not be shared because data use agreements restrict redistribution of participant-level data.