DNMT3b 39179G>T polymorphism and risk of primary lung cancer in Koreans

Lee, Shin Yup; Lee, Jae Hee; Park, Jae Hyung; Kim, Eun Jin; Lee, Soo Jung; Jeon, Hyo Sung; Sohn, Ji Woong; Cha, Seung Ick; Kim, Chang Ho; Jung, Tae Hoon; Park, Jae Yong

Abstract

BACKGROUND: DNA methylation is the main mechanism of epigenetic modification of genes and plays an important role in carcinogenesis. The methylation of promoter can inactivate the tumor suppressor gene by repression of transcription. We investigated the relationship between the 39179G>T (-579bp from exon 1B) polymorphism in DNMT3b gene, which is involved in de novo methylation, and the risk of primary lung cancer in Koreans.
METHODS
The DNMT3b 39179G>T genotypes were determined using PCR-RFLP method in 392 primary lung cancer patients and 391 healthy controls who were frequency (1:1) matched based on age and sex.
RESULTS
Although the frequencies of GG, GT, TT genotypes among cases (0.8%, 19.9%, 79.3%, respectively) were not significantly different from those among controls (1.5%, 25.1%, 73.4%, respectively), the frequency of wild-type G allele among cases was significantly different from that of controls (14.1% vs 10.7%, p=0.05). The combined GT and GG genotype was associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.51~1.00, p=0.05] when TT genotype was used as reference. When the lung cancers were categorized by tumor histology, the combined GT and GG genotype was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.46, 95% CI=0.26~0.80, p=0.006). In adenocarcinoma, the decreased risk of the combined GT and GG genotype was statistically significant in older patients (>or=61 years, adjusted OR=0.23, 95% CI=0.09~0.58, p=0.002) and in heavier smokers (>or=35 pack years, adjusted OR=0.34, 95% CI=0.13~0.88, p=0.028) in stratification analyses.
CONCLUSION
DNMT3b 39179G>T polymorphism may be a genetic determinant of lung cancer, especially adenocarcinoma in Koreans.