Association of the MMP12 rs652438 Variant with Lung Cancer Susceptibility: A Smoking-Stratified Analysis

Background: Matrix metalloproteinase 12 (MMP12) participates in extracellular-matrix remodeling and smoking-related pulmonary inflammation. This study evaluated the associations of MMP12 rs2276109 and rs652438 with lung cancer susceptibility in a Taiwanese population and examined rs652438 according to smoking status. Materials and Methods: This case–control study included 358 patients with histologically confirmed lung cancer and 716 age- and sex-matched cancer-free controls. Genotypes were determined using polymerase chain reaction–restriction fragment length polymorphism analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated under genotype, dominant, recessive, and allele models. Smoking-stratified estimates were adjusted for age and sex. Results: rs2276109 was not associated with lung cancer susceptibility. For rs652438, the CC genotype was associated with higher odds of lung cancer than the TT genotype (OR = 4.68, 95% CI = 2.00–10.99, p = 0.0003). Associations were also observed under the recessive (OR = 4.41, 95% CI = 1.89–10.32) and dominant (OR = 1.51, 95% CI = 1.12–2.03) models. The C allele was associated with higher lung cancer odds (OR = 1.62, 95% CI = 1.25–2.11). Among ever-smokers, the CC genotype remained associated with lung cancer after adjustment for age and sex (adjusted OR = 5.63, 95% CI = 2.17–15.38), whereas no significant association was observed among non-smokers. Conclusions:MMP12 rs652438, but not rs2276109, was associated with lung cancer susceptibility in this Taiwanese population. The association was more apparent among ever-smokers, although formal genotype-smoking interaction analyses were not statistically significant. Independent replication and functional investigation are warranted.