Abstract
Objectives
Lung cancer is a leading cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) being the predominant form. Genetic factors significantly influence individual susceptibility. This study investigated the association of TP63 (rs7631358) and CIR1 (rs13009079) polymorphisms with NSCLC risk in a Chinese population.Methods
A case-control study was conducted with 500 NSCLC patients and 500 matched controls. Genotyping was performed using the SEQUENOM MassARRAY platform. Associations were evaluated using chi-square tests and logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results
In the pre-specified primary analysis with FDR correction, both TP63 rs7631358 (A/G + A/A vs. G/G: adjusted OR = 1.409, FDR P = 0.030) and CIR1 rs13009079 (T/T vs. C/T + C/C: adjusted OR = 1.390, FDR P = 0.030) were significantly associated with an increased risk of lung adenocarcinoma after adjustment for smoking status, gender, and age. Exploratory subgroup analyses suggested that the TP63 association was more pronounced among ever-smokers, although the gene-smoking interaction did not reach statistical significance.Conclusions
TP63 rs7631358 and CIR1 rs13009079 polymorphisms are significantly associated with the susceptibility to lung adenocarcinoma in the Chinese Han population after correction for multiple testing. These findings support a role for the TP63-mediated DNA damage response pathway and the CIR1-Notch signaling pathway in ADC pathogenesis. Replication in larger, independent cohorts is warranted to confirm these associations and to further evaluate their potential for clinical risk stratification.