Background: Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in theCOX-2gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the8473T>Cpolymorphism in the 3'-untranslated region of theCOX-2gene and the risk of lung cancer in a Korean population.Methods: TheCOX-2genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.Results: The distribution of theCOX-2 8473T>Cgenotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined8473 TC+CCgenotype was associated with a significantly decreased risk of adenocarcinoma as compared with the8473 TTgenotype (adjusted OR = 0.64; 95% CI = 0.46–0.90,P= 0.01). On the stratification analysis, the protective effect of the combined8473 TC+CCgenotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91,P= 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93,P= 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87,P= 0.01, respectively).Conclusion: These findings suggest that theCOX-2 8473T>Cpolymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.

Background: Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in theEGFRgene and the risk of lung cancer in a Korean population.Methods: We first examined the frequencies of 39 candidate polymorphisms in theEGFRgene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls.Results: Of the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P= 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45–0.88,P= 0.007). When the analyses were stratified by smoking status, the protective effect of the TT genotype was statistically significant in ever-smokers (adjusted OR = 0.59, 95% CI = 0.41–0.86,P= 0.007), but not in never-smokers (adjusted OR = 0.89, 95% CI = 0.45–1.75,P= 0.73;P= 0.08, test for homogeneity). Consistent with the results of the genotyping analysis, the CGGCT haplotype with the 181946C allele was associated with a significantly increased risk of lung cancer compared to the CGGTT haplotype carrying the 181946T allele (adjusted OR = 1.50, 95% CI = 1.09–2.07,P= 0.012 and Bonferroni correctedP-value = 0.048).Conclusion: These results suggest that theEGFRpolymorphisms, particularly the 181945C>T polymorphism, could be used as markers for the genetic susceptibility to lung cancer.

Yoo SS, et al. J Korean Med Sci. 2015 Oct;30(10):1423-1428. https://doi.org/10.3346/jkms.2015.30.10.1423