Carcinogenesis Advance Access originally published online on June 13, 2006
Carcinogenesis 2006 27(11):2217-2222; doi:10.1093/carcin/bgl084
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Novel polymorphisms in the SUV39H2 histone methyltransferase and the risk of lung cancer
Research Institute and Hospital, National Cancer Center Goyang, Gyeonggi, Korea
1 Research Institute of Science for Aging, Yonsei University Seoul, Korea
*To whom correspondence should be addressed at: National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang, Gyeonggi 411-769, South Korea. Tel: +82 31 920 1601; Fax: +82 31 920 1520; Email: jinslee{at}ncc.re.kr
Histone H3 lysine 9 (H3-K9) methylation and DNA methylation are important features of mammalian heterochromatin. Suppressor of variegation 3-9 homolog 2 (SUV39H2) is the histone methyltransferase that is required to methylate H3-K9, leading to transcriptional repression or silencing of target genes. In this study, we investigated the association of SUV39H2 polymorphisms and the risk of lung cancer. From the results of PCR direct sequencing, eight single nucleotide polymorphisms (SNPs) of SUV39H2 were identified in Korean population. In a hospital-based study of 346 lung cancer patients and 423 healthy controls, a novel SNP in the 3'-UTR of SUV39H2 (1624 G
C) was associated with a statistically significant increase in lung cancer risk. Compared to the G/G genotype, genotypes with 1624C allele (G/C + C/C) significantly increased the susceptibility to lung cancer with adjusted odds ratio (AOR) of 2.63 (95% confidence interval (CI)= 1.10–6.29) for ever-smokers, especially in the older age group (age 
55 years). Specifically, the variant genotype of 1624SNP was significantly associated with an increased risk of squamous cell carcinoma (AOR, 3.52; 95% CI = 1.13–9.45) in the older age group, while no significant association was found in patients with other histology. This study provided the first evidence that a novel SUV39H2 polymorphism may be an important predictive marker for lung cancer susceptibility for the smokers.
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