Suv39h2 Polymorphisms And The Risk Of Lung Cancer.

B. Hwangbo,In-Ho Kim, H. J. Kee,Hyo Song Kim, Cheong Soo Park, J. M. Kim, C. G. Park,Y. K. Jang,Jae-Gahb Park,J. Lee

JOURNAL OF CLINICAL ONCOLOGY(2005)

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Abstract
9582 Background: Histone methylation is an important step for forming heterochromatin and the regulation of gene functions. SUV39H methyltrasferase, which targets histone H3 lysine 9, has two types of genes in human, SUV39H1 and SUV39H2. SUV39H1 was found to interact with Rb protein and Suv39h1/h2 double knockout mice had an increased risk of lymphoma. We investigated the relation of SUV39H2 polymorphisms and lung cancer. Methods: Among 8 novel SNPs identified on the SUV39H2 gene through direct PCR sequence, we examined 6004G/C (3’ UTR) polymorphism on DNA samples from 348 (M/F= 237/111) lung cancer (LC) cases and 423 (M/F=242/181) controls without cancer (NC) using an automatic direct sequencing and a real-time PCR (TaqMan assay). Results: The minor allele frequency was 9.8% and 7.1% for LC and NC, respectively. There was no effect of gender or smoking status on genotype distribution. The distribution of non-wild genotype (GC + CC) by smoking status and age group (<55 vs. ≥55 years) is shown in the table. Overall, non-wild genotype was associated with a modest increase in the risk of lung cancer compared to GG genotype for ever-smokers (OR=1.73, 95% CI=0.99–3.05) but not for never-smokers (OR=1.02, 95% CI=0.54–1.93). This SUV39H2 genotype-associated increase in the risk of lung cancer was more pronounced in the old age group ever-smokers (OR=2.47, 95% CI=1.06–5.75). Conclusion: SUV39H2 6004G/C (3’ UTR) polymorphism was associated with an increased risk of lung cancer in smokers, which became apparent in the old age group. More studies are needed to elaborate the role of SUV39H2 in carcinogenesis and gene-environment interaction. (Supported in part by NCC grant 0210040) No significant financial relationships to disclose.
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Key words
RNA methylation,Histone Methylation,mRNA modification
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