Novel polymorphisms in the SUV39H2 histone methyltransferase and the risk of lung cancer.
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 >or=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.
Yoon
Kyong-Ah
KA
Research Institute and Hospital, National Cancer Center Goyang, Gyeonggi, Korea.
Hwangbo
Bin
B
Kim
Il-Jin
IJ
Park
Sohee
S
Kim
Hee Sun
HS
Kee
Hyun Jung
HJ
Lee
Jong Eun
JE
Jang
Yeun Kyu
YK
Park
Jae-Gahb
JG
Lee
Jin Soo
JS
D020413:3' Untranslated Regions; D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011496:Protein Methyltransferases; D012306:Risk; D012907:Smoking
D020413:3' Untranslated Regions; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C515701:SUV39H2 protein, human