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Polymorphisms of drug-metabolizing genes and risk of non-Hodgkin lymphoma
Kim, Hee Nam,Kim, Nan Young,Yu, Li,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min-Ho,Park, Kyeong-Soo,Choi, Jin-Su,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2009 American journal of hematology Vol.84 No.12
<P>Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)<SUB>AG</SUB> = 0.67, 95% confidence interval (CI) = 0.55–0.82; OR<SUB>AG/GG</SUB> = 0.66, 95% CI = 0.54–0.80) and DLBCL (OR<SUB>AG</SUB> = 0.63, 95% CI = 0.49–0.82; OR<SUB>AG/GG</SUB> = 0.64, 95% CI = 0.50–0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR<SUB>AG/GG</SUB> = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR<SUB>AG</SUB> = 1.28, 95% CI = 1.07–1.54; OR<SUB>AG/GG</SUB> = 1.26, 95% CI = 1.06–1.51) and DLBCL (OR<SUB>AG</SUB> = 1.32, 95% CI = 1.04–1.66; OR<SUB>AG/GG</SUB> = 1.30, 95% CI = 1.03–1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.</P>
Association with TP53 codon 72 polymorphism and the risk of non-Hodgkin lymphoma
Kim, Hee Nam,Yu, Li,Kim, Nan Young,Lee, Il-Kwon,Kim, Yeo-Kyeoung,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min–,Ho,Park, Kyeong-Soo,Choi, Jin-Su,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2010 American journal of hematology Vol.85 No.10
Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma
Kim, Hee Nam,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Lee, Je-Jung,Yang, Deok-Hwan,Park, Kyeong-Soo,Choi, Jin-Su,Park, Moo Rim,Jo, Deog Yeon,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2007 American journal of hematology Vol.82 No.9
<P>Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate-dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population-based case-control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population-based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R→3R) and 6-bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower risk of MM (OR = 0.66, 95%CI; 0.43–0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R and 6-bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R, and 6-bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc.</P>
Polymorphisms in DNA Repair Genes and <i>MDR1</i> and the Risk for Non-Hodgkin Lymphoma
Kim, Hee Nam,Kim, Nan Young,Yu, Li,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min-Ho,Park, Kyeong-Soo,Choi, Jin-Su,Kim, Hyeoung-Joon Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.4
<P>The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (<I>XRCC1</I> 399 GA, <I>OGG1</I> 326 GG, <I>BRCA1</I> 871 TT, and <I>WRN</I> 787 TT) were associated with a decreased risk for NHL [odds ratio (<I>OR</I>)<SUB>XRCC1 GA</SUB> = 0.80, <I>p</I> = 0.02; <I>OR</I><SUB>OGG1 GG</SUB> = 0.70, <I>p</I> = 0.008; <I>OR</I><SUB>BRCA1 TT</SUB> = 0.71, <I>p</I> = 0.048; <I>OR</I><SUB>WRN TT</SUB> = 0.68, <I>p</I> = 0.01]. Conversely, the <I>MGMT</I> 115 CT genotype was associated with an increased risk for NHL (<I>OR</I> = 1.25, <I>p</I> = 0.04). In the <I>MDR1</I> gene, the 1236 CC genotype was associated with a decreased risk for NHL (<I>OR</I> = 0.74, <I>p</I> = 0.04), and the 3435 CT and TT genotypes were associated with an increased risk (<I>OR</I><SUB>3435CT</SUB> = 1.50, <I>p</I> < 0.0001; <I>OR</I><SUB>3435TT</SUB> = 1.43, <I>p</I> = 0.02). These results suggest that polymorphisms in the DNA repair genes <I>XRCC1</I>, <I>OGG1</I>, <I>BRCA1</I>, <I>WRN1</I>, and <I>MGMT</I> and in the <I>MDR1</I> gene may affect the risk for NHL in Korean patients.</P>
Association between folate-metabolizing pathway polymorphism and non-Hodgkin lymphoma
Kim, Hee Nam,Lee, Il-Kwon,Kim, Yeo-Kyeoung,Tran, Huong Thi Thanh,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min–,Ho,Park, Kyeong-Soo,Shin, Myung-Geun,Choi, Jin-Su,Kim, Hyeoung-Joon Blackwell Publishing Ltd 2008 British journal of haematology Vol.140 No.3
<P>Summary</P><P>Polymorphisms in the genes coding folate-metabolizing enzymes affect the risk of some forms of cancer. We investigated the association between these polymorphisms and non-Hodgkin lymphoma (NHL) risk in a population-based study (583 cases and 1700 controls). The <I>MTHFR</I> 677TT and CT genotypes were associated with reduced risk for NHL [odds ratios (OR) = 0·79; 95% confidence intervals (CI) = 0·65–0·98 for 677CT and 0·61; 0·45–0·82 for 677TT] and diffuse large B-cell lymphoma (DLBCL) (OR = 0·68; 0·51–0·88 for 677CT; OR = 0·56; 0·38–0·83 for 677TT). The <I>MTHFR</I> 1298CC genotype was associated with increased risk for NHL (OR = 1·71; 1·07–2·75) and T-cell lymphoma (OR = 3·05; 1·53-6·11). The <I>MTRR</I> 66GG genotype was associated with increased risk for DLBCL (OR = 1·56; 1·03-2·38) and the <I>TYMS</I> 2R2R genotype was associated with increased risk for T-cell lymphoma (OR = 2·83; 1·33–6·01). Using subjects with 3RG3RG as a reference group, <I>TYMS</I> 2R2R was associated with increased risk for T-cell lymphoma (OR = 2·46; 1·04–5·79). Interestingly, we observed a reduced association between the <I>TYMS</I> 2R3RG genotype and DLBCL (OR = 0·61; 0·38–0·99). These results suggest that <I>MTHFR</I>, <I>MTRR</I> and <I>TYMS</I> polymorphisms may play a significant role in the risk for NHL.</P>
Yang, Deok-Hwan,Kim, Mi-Hyun,Lee, Youn-Kyung,Hong, Cheol Yi,Lee, Hyun Ju,Nguyen-Pham, Thanh-Nhan,Bae, Soo Young,Ahn, Jae-Sook,Kim, Yeo-Kyeoung,Chung, Ik-Joo,Kim, Hyeoung-Joon,Kalinski, Pawel,Lee, Je-J Springer International 2011 Annals of hematology Vol.90 No.12
<P>For wide application of a dendritic cell (DC) vaccination in myeloma patients, easily available tumor antigens should be developed. We investigated the feasibility of cellular immunotherapy using autologous alpha-type 1-polarized dendritic cells (관DC1s) loaded with apoptotic allogeneic myeloma cells, which could generate myeloma-specific cytotoxic T lymphocytes (CTLs) against autologous myeloma cells in myeloma patients. Monocyte-derived DCs were matured by adding the 관DC1-polarizing cocktail (TNF관/IL-1관/IFN-관/IFN-관/poly-I:C) and loaded with apoptotic allogeneic CD138(+) myeloma cells from other patients with matched monoclonal immunoglobulins as a tumor antigen. There were no differences in the phenotypic expression between 관DC1s loaded with apoptotic autologous and allogeneic myeloma cells. Autologous 관DC1s effectively took up apoptotic allogeneic myeloma cells from other patients with matched subtype. Myeloma-specific CTLs against autologous target cells were successfully induced by 관DC1s loaded with allogeneic tumor antigen. The cross-presentation of apoptotic allogeneic myeloma cells to 관DC1s could generate CTL responses between myeloma patients with individual matched monoclonal immunoglobulins. There was no difference in CTL responses between 관DC1s loaded with autologous tumor antigen and allogeneic tumor antigen against targeting patient's myeloma cells. Our data indicate that autologous DCs loaded with allogeneic myeloma cells with matched immunoglobulin can generate potent myeloma-specific CTL responses against autologous myeloma cells and can be a highly feasible and effective method for cellular immunotherapy in myeloma patients.</P>