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Significant Association of Cyclin Dependent Kinase Inhibitor 1B Genotypes With Lung Cancer Risk Among Smokers
Te-Chun Shen1,2,3, Ya-Chen Yang4, Chia-Hsiang Li1,5
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Background/Aim:
Lung cancer remains the leading cause of cancer-related mortality worldwide, and cigarette smoking is its predominant factor. However, genetic biomarkers contributing to susceptibility, particularly within cell-cycle regulatory genes such as cyclin dependent kinase inhibitor 1B (CDKN1B), remain incompletely identified. The study aimed to investigate the contribution of CDKN1B rs34330 and rs2066827 polymorphisms to lung cancer risk, and to evaluate their interaction with smoking behavior in a Taiwanese cohort.
Materials And Methods:
The CDKN1B genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Genotypic and allelic distributions were compared using chi-square tests, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Stratified analyses were performed according to smoking status.
Results:
No significant association was observed between CT (OR=1.20, 95%CI=0.87-1.66, p=0.2928) or TT (OR=1.26, 95%CI=0.87-1.83, p=0.2656) rs34330 genotypes and lung cancer risk. Similarly, in dominant (OR=1.22, 95%CI=0.90-1.66, p=0.2302) and recessive models (OR=1.11, 95%CI=0.82-1.49, p=0.5576), no significant association were found. Allelic analysis confirmed no difference for rs34330 T allele (p=0.2654) or rs2066827 G allele (p=0.8868). However, among smokers, rs34330 TT genotype carriers exhibited significantly elevated lung cancer risk (OR=1.59, 95%CI=1.05-2.42, p=0.0372), persisting after adjustment for age and sex (OR=1.64, 95%CI=1.07-2.36). This is not found among non-smokers.
Conclusion:
Although CDKN1B polymorphisms are not independently associated with lung cancer susceptibility, rs34330 may interact with cigarette smoking to elevate its risk. These findings suggest a potential gene-environment interaction influencing smoking-related lung carcinogenesis and warrant further validation in larger multi-ethnic populations.
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