Carcinogenesis Advance Access published online on August 11, 2007
Carcinogenesis, doi:10.1093/carcin/bgm156
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Genetic polymorphisms in the Rb-binding zinc finger gene RIZ and the risk of lung cancer
1 Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea
2 National Cancer Control Research Institute, Goyang, Gyeonggi, Korea
3 Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea
4 Department of Epidemiology, The Graduate School of Public Health, Seoul National University, Seoul, Korea
Correspondence to: Dr. Jin Soo Lee, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang, Gyeonggi, 411-769, South Korea, Telephone: +82-31-920-1601; Fax: +82-31-920-1520; e-mail: jinslee{at}ncc.re.kr.
Histone methyltransferase (HMT) enzymes that methylate the lysine of histones are involved in chromatin-mediated gene expression. Previously, we reported that a novel polymorphism of SUV39H2, the HMT that is required for the methylation of H3-K9, was associated with an increased risk of lung cancer in Koreans. The retinoblastoma protein-interacting zinc finger gene RIZ (PRDM2) is also a member of a histone/protein methyltransferase superfamily, and the inactivation of RIZ in many cancers was detected as frameshift mutations, hypermethylation, and missense mutations. In this study, we show the association of RIZ polymorphisms with the risk of lung cancer. In a hospital-based study of 335 lung cancer patients and 335 age- and gender- matched healthy controls, 120 polymorphisms of RIZ were screened. Of the 120 genotyped SNPs, 42 SNPs were selected for the statistical analysis based on their frequency (>5%) and linkage disequilibrium (LD; only a representative SNP was analyzed if there were absolute LDs [r2 = 1]); this resulted in three LD blocks. The +92337G>A and +95701C>A polymorphisms showed a statistically significant association with the reduced risk of lung adenocarcinomas after correcting the P values for multiple testing (for carrying one variant allele vs. none, adjusted OR (aOR) = 0.55 (95% CI, 0.38–0.78), corrected P = 0.04; aOR = 0.54 (95% CI, 0.38–0.77), corrected P = 0.02, respectively). One haplotype (Ht5) in LD block 3 of RIZ was significantly associated with the reduced risk of lung adenocarcinomas (aOR = 0.28, 95% CI = 0.13–0.58) as well as overall lung cancer (aOR = 0.50, 95% CI = 0.30–0.82). This study suggested that RIZ polymorphisms may be important predictive markers for lung cancer susceptibility.
Key Words: RIZ (PRDM2) • single nucleotide polymorphism • lung cancer • adenocarcionoma
Received February 5, 2007; revised June 27, 2007; accepted June 28, 2007.