A Rare Case of Pediatric T Lymphoblastic Leukemia With t(11;17)(q23;q21) Involving Mixed-Lineage Leukemia Gene Rearrangement

No abstract available.

Usefulness of Serum Thymidine Kinase 1 as a Biomarker for Aggressive Clinical Behavior in B-cell Lymphoma

BACKGROUND: The cell cycle-dependent enzyme thymidine kinase 1 (TK1) is known to increase during cancer cell proliferation and has been reported as a prognostic marker for various hematologic malignancies and solid tumors. This study aimed to determine the reference interval in Korean healthy controls and to evaluate the usefulness of TK1 as a biomarker for aggressive clinical behavior in B-cell lymphoma patients. METHODS: We enrolled 72 previously untreated patients with B-cell lymphoma and 143 healthy controls. Serum TK1 levels were measured by chemiluminescence immunoassay (Liaison(R), DiaSorin, USA). We established the reference intervals in healthy controls. The diagnostic performance of serum TK1 was studied using receiver operating characteristic (ROC) analysis, and the correlation between the cutoff level for serum TK1 and clinical characteristics of B-cell lymphoma was evaluated. RESULTS: The reference range (95th percentile) of serum TK1 in healthy controls was 5.4-21.8 U/L. There was a clear difference in TK1 levels between patients with B-cell lymphoma and healthy controls (40.6+/-68.5 vs. 11.8+/-4.4 U/L, P or =15.2 U/L) correlated with the advanced clinical stage (P<0.001), bone marrow involvement (P=0.013), international prognostic index score (P=0.001), lactate dehydrogenase level (P=0.001), low Hb level (<12 g/dL) (P=0.028), and lymphocyte count (P=0.023). CONCLUSIONS: The serum TK1 level could serve as a useful biomarker for aggressive clinical behavior in B-cell lymphoma patients.

Comparison of Serum Fibrin-Fibrinogen Degradation Products with Carcinoembryonic Antigen as Biomarkers for Colon Cancer / 임상검사와정도관리

BACKGROUND: Colon cancer is the second most common cancer in males and fourth most common in females in Korea. The levels of serum fibrin-fibrinogen degradation products (FDP) are elevated in many malignancies due to haemostatic alterations resulting from carcinogenesis. We compared serum FDP with carcinoembryonic antigen (CEA) to assess whether FDP has a diagnostic value for colon cancer. METHODS: A total of 177 serum samples from 95 colon cancer patients and 82 healthy controls were provided by the Korea Cancer Center Hospital biobank. Serum FDP levels were measured using the DR-70 detection kits (AMDL, USA) and the levels of serum CEA were measured using the Roche E170 Analytics (Roche Diagnostics, Germany). RESULTS: The mean serum FDP and serum CEA levels were significantly higher in the cancer patient group (FDP, 1.65+/-1.44 microg/mL; range, 0.36 to 9.48; CEA, 99.99+/-321.74 ng/mL; range, 1.46 to 2,170.00) than in the control group (FDP, 0.58+/-0.46 microg/mL; range, 0.02 to 3.27, P<0.05; CEA, 1.66+/-1.18 ng/mL; range, 0.20 to 6.38, P<0.05). The receiver operating characteristic curve for FDP showed 80% clinical sensitivity and 83% specificity with an optimal cut-off of 0.81 microg/mL, while that for CEA exhibited 84% sensitivity and 94% specificity with a cut-off of 3.51 ng/mL. The area under the curve was 0.87 and 0.96 for serum FDP and CEA, respectively. A combination of the two markers showed 90% clinical sensitivity and 92% specificity for colon cancer. CONCLUSIONS: The diagnostic sensitivity for colon cancer was increased by using a combination of FDP and CEA.

A Case of Hepatosplenic T-cell Lymphoma Diagnosed by Bone Marrow Examination

Hepatosplenic T-cell lymphoma (HSTL) is a condition in which lymphoma cells infiltrate the sinusoids of the liver, spleen, and bone marrow, without lymph node involvement. We encountered a case of hepatosplenic T-cell lymphoma in a Vietnamese woman. The patient was hospitalized with epigastric pain and nausea. Splenomegaly and multiple poorly defined, low-attenuating nodular lesions in the liver were visualized on computed tomography (CT), and thrombocytopenia was noted. The lymph nodes were not significantly enlarged. Splenic biopsy could not be performed because of severe thrombocytopenia. Neoplastic lymphoid cells were present in bone marrow aspirates. Bone marrow sections revealed infiltration of CD3(+) and CD20(-) neoplastic lymphoid cells in the sinusoids. A clonality assay (IdentiClone T-Cell Receptor Delta Gene Clonality Assay; Invivoscribe Technologies, USA) showed gene rearrangements in the T-cell receptor delta gene. Thus, we made a confirmatory diagnosis of HSTL. When splenic biopsy is not available, bone marrow aspirates and clonality assessment may become useful diagnostic tools.

Utilization of Mean Peroxidase Index for Discrimination of Pseudoneutropenia

BACKGROUND: Autoanalyzer ADVIA2120 uses intracellular peroxidase concentration to perform white blood cell (WBC) differential. Therefore, in specimens containing neutrophils with low peroxidase concentration, neutrophils can be miscounted as monocytes or large unstained cells resulting in pseudoneutropenia. Myeloperoxidase deficiency can be detected by the mean peroxidase index (MPXI). The aims of this study are to establish the reference interval of MPXI and define a cut off value for manual slide review to discriminate pseudoneutropenia. METHODS: We calculated reference intervals as mean+/-2SD according to the indirect method of CLSI C28-A3 guideline from MPXI data of 5,802 individuals who took routine health checkup from April 2010 to June 2012. We performed manual slide review on specimens with low MPXI and compared neutrophil differential count of manual method with that of autoanalyzer. When neutrophil differential in manual slide review was >20%P higher than autoanalyzer result, it was regarded as a pseudoneutropenia. We performed ROC analysis using the MPXI results of samples with and without pseudoneutropenia to define a cutoff to discriminate pseudoneutropenia. RESULTS: The reference intervals of MPXI in total population, male, and female were -4.9 to 7.5, -5.5 to 7.3, and -4.5 to 7.5, respectively. The mean value of MPXI was significantly higher in female than in male and there was no difference by age. Twenty-two pseudoneutropenia samples from 7 patients were identified. ROC analysis yielded cutoff value of -20.7 with 94.9% of sensitivity and 77.3% of specificity. CONCLUSIONS: MPXI may be used in the manual slide review guideline for detecting pseudoneutropenia.

Type Distribution of Unexpected Red Cell Antibodies in Patients with Malignancy / 대한수혈학회지

BACKGROUND: Performance of antibody screening and identification tests before blood transfusion is important because the unexpected presence of red cell antibodies may cause hemolytic transfusion reactions. Many patients with malignancy undergo transfusion in order to overcome pancytopenia due to disease itself or chemotherapy. We investigated the type distribution of unexpected red cell antibodies in cancer patients and compared our results with those of other institutions. METHODS: From January 2008 to June 2011, 30,989 serum samples were screened using a LISS/Coombs card and ID-DiaCell I, II (DiaMed AG, Morat, Switzerland). Data-Cyte Plus Reagent Red Blood Cells (Medion Diagnostics, Dudingen, Switzerland) were used in performance of antibody identification tests. RESULTS: Out of 30,989 serum samples, 180 cases (0.58%) showed screening-positive results, and unexpected antibodies were identified in 72 cases. The type of unexpected antibody observed most often in cancer patients was a member of the Rh antibody group, anti-E in 17 cases (29.8%), followed by anti-Lea in five cases (8.8%) and anti-e in three cases (5.3%). While Rh group antibodies were observed in the colon cancer group, non-Rh group antibodies were observed in the rectal cancer group. And, in the genitourinary cancer group, Lewis group antibodies were more frequently detected than others. CONCLUSION: Findings from our study demonstrated a type distribution of unexpected red cell antibodies that was similar to those reported in previous studies. Compared with non-cancerous patients, no difference in type distribution of unexpected red cell antibodies was observed in cancer patients. Some antibodies were frequently observed in certain cancer groups. Further comprehensive research on unexpected antibodies based on location or histologic type of cancer is needed.

Clinical Significance of Oligoclonal Bands in Patients with Multiple Myeloma after Autologous Stem Cell Transplantation

BACKGROUND: Oligoclonal bands or isotype switch detectable by serum immunofixation electrophoresis (IFE) has been reported following chemotherapy and stem cell transplantation in patients with multiple myeloma (MM). We studied the significance of oligoclonal bands appearing after chemotherapy and autologous stem cell transplantation (ASCT) in Korean MM patients, and its impact on relapse. And we investigated the serial serum free light chain (FLC) ratio to establish its possible relationship with the relapse of MM. METHODS: We conducted a retrospective analysis of the serial serum IFE and FLC ratio in 16 MM patients treated with chemotherapy and ASCT. RESULTS: Eleven out of 16 patients (68.8%) had oligoclonal bands with or without isotype switch after ASCT and the median interval from transplantation was 2.0 months. And relapse or persistence rate of monoclonal gammopathy was lower in patients with oligoclonal bands (27.3% vs. 60.0%), though without statistical significance (P=0.299). In eight patients who developed oligoclonal bands and did not relapse, the serial serum FLC ratio was normal in range. But one patient who developed oligoclonal bands and showed increase of plasma cells in bone marrow, the serial serum FLC ratio was abnormal in range. CONCLUSIONS: The occurrence of oligoclonal bands after chemotherapy and ASCT in Korean MM patients is not significantly associated with adverse consequence of relapse or persistence of monoclonal gammopathy. Therefore oligoclonal bands may be not bad prognostic criterion. And the measurement of serum FLC ratio may be a useful indicator to predict relapse in MM patients who developed oligoclonal bands.

A Case of Heterozygous alpha(+)-Thalassemia Diagnosed in a Korean Family by Using Multiplex Ligation-Dependent Probe Amplification / 임상검사와정도관리

Alpha-thalassemia (alpha-thalassemia), which is prevalent in the Mediterranean region, is caused by deficient synthesis of the alpha-globin chains. It is commonly caused by HBA1 and/or HBA2 gene deletion and is diagnosed by DNA sequence analysis. The proband was a 38-year-old woman who was found to have microcytic and hypochromic anemia on a routine health checkup. Results of the Hb electrophoresis (EP) and direct sequencing of the HBA1 and HBA2 genes were found to be normal. As multiplex ligation-dependent probe amplification (MLPA) for the HBA1 and HBA2 genes revealed heterozygous deletion, she was diagnosed with heterozygous alpha+-thalassemia. Although routine laboratory tests revealed similar findings in the proband's father, brother and niece, MLPA revealed heterozygous deletions of the HBA1 or HBA2 gene in her brother and niece. In summary, we report a case of heterozygous alpha+-thalassemia in a Korean family that was detected by MLPA. We recommend that patients with suspected hemoglobinopathies should be followed-up further with MLPA, especially when Hb EP shows a normal pattern.

A Case of a 63-bp Deletion in the mpt64 Gene of Mycobacterium tuberculosis Strains Which Showed False Negativity in the Immunochromatographic Assay / 대한임상미생물학회지

Mycobacterium tuberculosis complex (MTBC) is discriminated from non-tuberculous mycobacteria (NTM) via an immunochromatographic assay (ICA) which is based on the reactions of monoclonal antibodies against MPT64, one of the predominant proteins excreted by MTBC. Recently, the authors of the present study discovered SD TB-negative Mycobacterium tuberculosis strains. In addition, sequence analysis of the mpt64 genes in these strains was performed and showed a deletion of 63 bp from nucleotides 196 to 258. In cases of MPT64-negative mycobacterium, the authors recommend performing TB PCR for correct diagnosis.

Development of Indicators to Assess the Stability of Remnant Blood Samples Stored in a Biobank: Experience at One Institution / 대한진단검사의학회지

BACKGROUND: One of the major concerns with biobanking is the absence of standard operating procedures to eliminate pre-analytical variation arising from sample collection, preparation, and storage. Currently, there is a lack of tools to carry out quality control procedures for stored blood samples. The aim of this study is to assess the quality of stored blood samples in our biobank and to suggest appropriate indicators for their quality control. METHODS: The stored blood samples that we tested have been registered into our biobank since 2003. These were transferred to our biobank after carrying out routine requested tests, because the samples would have otherwise been discarded. For the purpose of quality control, we analyzed the concentrations and the integrity of DNA and RNA extracted from the stored samples and tested the levels of several serum proteins; the results were compared with the corresponding pre-storage levels. RESULTS: A total of 19 samples were stored from 2006 to 2009. Of the 22 samples stored between 2003 and 2005, 50% showed complete DNA integrity. However, sufficient RNA integrity was noted in only 1 sample stored as recently as 2009. High blood urea nitrogen levels were also noted in the stored sera, but the increase did not correlate to the duration of storage. CONCLUSIONS: The amount and integrity of nucleic acids extracted from stored blood samples are potential indicators that can be used for quality control. A guideline for the quality assessment of stored blood samples in a biobank is urgently needed.

Late-onset Neutropenia Following Rituximab Therapy as a Treatment of Diffuse Large B-cell Lymphoma: A Single Institution Study / 대한진단검사의학회지

BACKGROUND: Late-onset neutropenia (LON) following rituximab therapy has been reported in recent years. However, its incidence has not been reported in Korea. The aim of this study is to investigate the incidence of LON after rituximab therapy in Korean patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-eight cases of DLBCL treated with rituximab between 2004 and 2008 were evaluated. We identified LON as defined by the neutrophil count of <1.5x10(9)/L without apparent cause after the recovery of neutrophil count following rituximab therapy. Bone marrow aspiration and biopsy specimens at the time of neutropenia were available for retrospective review in only 5 of the patients. RESULTS: LON was observed in 15 (15.3%) of the 98 patients. In the bone marrow specimens of the 5 patients, promyelocytes were relatively increased and the maturation index of the granulopoiesis was 2:1-3:1, which reflects maturation arrest. CONCLUSIONS: The incidence of LON following rituximab therapy was 15.3% in Korean patients with DLBCL. Although there are several hypotheses about the causative mechanisms of LON, we suggest that maturation arrest at the promyelocyte stage of granulopoiesis may be one of the mechanisms involved in the development of LON.

A Case of del(16)(q22) in a Patient with Acute Myeloid Leukemia with Complex Karyotype / 대한진단검사의학회지

Inversion of chromosome 16 [inv(16)(p13.1q22)] and t(16;16)(p13.1;q22) are associated with acute myelomonocytic leukemia (AMML) with eosinophilia and a favorable prognosis. On the other hand, patients with del(16)(q22) usually present with MDS or chronic myelomonocytic leukemia (CMML), which can evolve to AMML without eosinophilia, and this chromosomal aberration is associated with older age, a complex karyotype, and a poor prognosis. We report a case of AML with del(16)(q22) which showed a complex karyotype, absence of eosinophilia in bone marrow study and a poor response to chemotherapy.

HDL Cholesterol Reduction during Rosiglitazone and Fenofibrate Treatment in a Type 2 Diabetes Mellitus Patient with Dyslipidemia / 대한진단검사의학회지

Thiazolidinediones (TZD), which are widely used as insulin sensitizers, and fibrates, which are lipid-lowering drugs, are used in the treatment of dyslipidemia that commonly accompanies diabetes. Several reports suggest elevated levels of high-density lipoprotein (HDL) cholesterol, but the paradoxical reduction of HDL cholesterol level during single or combined TZD and fibrate therapies has been occasionally reported. Herein, we report a case of paradoxical decrease in HDL cholesterol and apolipoprotein A-1 levels during rosiglitazone and fenofibrate treatment for the first time in Korea. The patient was a 56-yr-old man presenting with type 2 diabetes mellitus and dyslipidemia. His HDL cholesterol and apolipoprotein A-1 levels returned to normal after the cessation of fenofibrate therapy. Since diabetes is an established risk factor of cardiovascular diseases, low HDL cholesterol can be a key cause of concern for patients with diabetes. Therefore, HDL cholesterol level should be determined before and after starting TZD and/or fibrate therapy in diabetic patients.

Near-tetraploidy Acute Myeloid Leukemia with RUNX1-RUNX1T1 Rearrangement Due to Cryptic t(8;21) / 대한진단검사의학회지

Tetraploidy or near-tetraploidy is a rare cytogenetic abnormality found in AML, and is divided into primary and secondary forms. The secondary tetraploidy or near-tetraploidy found in AML is known to be specifically associated with t(8;21). In this case report, FISH analysis detected RUNX1-RUNX1T1 gene rearrangement in the absence of cytogenetic abnormality of t(8;21), which suggests the presence of unvailed t(8;21). This is the first case report of tetraploidy or near-tetraploidy AML with cryptic RUNX1/RUNX1T1 in Korea. Although the prognosis of tetraploidy or near- tetraploidy with t(8;21) is known to be poor, this patient shows a relatively good clinical course compared to other reported cases.

Evaluation of Artus HBV LC PCR kit using SLAN Real-time PCR / 임상검사와정도관리

BACKGROUND: Real-time PCR has been widely used not only for quantification?of disease-related genes but also for detection of bacteria or viruses. In this study, we evaluated the performance of Artus HBV LC PCR kit (Qiagen, Hilden, Germany) using recently developed SLAN real-time PCR detection system (Shanghai Hongshi Medical Technology Co., Shanghai, China) to assess clinical relevance of the new instrument. METHODS: Precision, linearity and detection limit of Artus HBV LC PCR kit were evaluated using SLAN real-time PCR detection system. We also compared the SLAN real-time PCR detection system with LightCycler 1.5 (Roche Molecular System, Branchburg, NJ, USA) and ABI PRISM 7500 (Applied Biosystems, Foster City, CA, USA). WHO International Standard for HBV DNA Nucleic Acid Amplification Techniques (NIBSC code:97/750) and 40 HBV DNA positive sera were tested for this evaluation. RESULTS: Within-run and between-day coefficients of variation were 5.63%, 4.01% at 6.2x10(3) IU/mL and 1.12%, 0.80% at 2.1x10(1) IU/mL, respectively. Linearity was verified from 1.0x10(1) to 1.0x10(5) IU/mL (r(2)=1.000; slope=1.1412). Detection limit for HBV DNA was verified to be 7.54 IU/mL. It showed a good correlation with LightCycler 1.5 (r=0.9723) and ABI PRISM 7500 (r=0.9768). CONCLUSIONS: Artus HBV LC PCR kit using SLAN real-time PCR detection system showed a good precision, linearity and assay sensitivity. It correlated well with LightCycler 1.5 and ABI PRISM 7500. We conclude that it can be used in clinical laboratories for nucleic acid quantification.

Availability of Fine Needle Aspirates for the Assessment of HER2 Gene Amplification in Invasive Breast Cancer Patients / 대한진단검사의학회지

BACKGROUND: FISH and immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue are currently used in the clinical laboratory to determine HER2 status in invasive breast cancer patients. Since tissue-based methods are relatively time-consuming and have a limitation for standardization of procedure, we evaluated the availability of fine needle aspirates (FNA) for the assessment of HER2 status in invasive breast cancer patients. METHODS: FNA were obtained from 51 invasive breast cancer patients and were submitted for the evaluation of HER2 status. After invasive breast cancer components were ascertained by morphological evaluation, HER2 gene amplification was evaluated by FISH. The results of HER2 FISH on FNA cells were compared with those of both FISH and IHC on corresponding FFPE tissues. FISH results were interpreted by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines issued in 2007. RESULTS: Of 51 FNA specimens, one was excluded due to an insufficient number of cancer cells for tests. Excluding the cases that showed 'equivocal' results, 47 (98%) out of 48 cases were concordant between the results of FISH on FNA and FISH on corresponding FFPE tissue (kappa, 0.969), and 43 (93%) out of 46 cases were concordant between the results of FISH on FNA and IHC on corresponding FFPE tissue (kappa, 0.912). CONCLUSIONS: An excellent correlation was found between FISH on FNA cells and corresponding FFPE sections. We recommend FNA specimens for more rapid determination of HER2 status by FISH, which will be helpful for patient selection for individualized therapy.

Four Cases of Hematologic Malignancy Following Radioactive Iodine Therapy for Thyroid Cancer / 대한진단검사의학회지

Ionizing radiation including I131 might produce chromosomal translocation, causing hematologic malignancy. The incidence of leukemia following radioactive iodine treatment for thyroid cancer has been reported to be approximately 0.1 to 2.0% in Western countries, whereas fewer cases have been reported in Korea. We hereby report four cases of secondary hematologic malignancy, who received iodine therapy for thyroid cancer after thyroidectomy: two cases of acute lymphoblastic leukemia with t(9;22)(q34;q11.2), a case of MDS with 5q deletion, and a case of MDS with normal karyotype. Three cases of hematologic malignancy have developed after cumulative dosage of less than 800 mCi. The treatment intervals in two cases were less than 12 months, and the other two cases had I131 therapy only once. Assessment of causality using the Naranjo probability scale for adverse drug reactions showed that a 'possible' relationship existed between the use of I131 and secondary hematologic malignancy in all of the four cases in this report.

Correlation of Chromosomal Aberrations with Prognostic Markers in Multiple Myeloma Patients- A Single Institution Study / 대한진단검사의학회지

BACKGROUND: Immunoglobulin heavy chain (IGH) gene rearrangement, 13q14 deletion and trisomy 1q are frequently observed in Korean patients with multiple myeloma. The purpose of our study was to analyze the statistical correlation between chromosomal aberrations and routine laboratory test results as prognostic markers and to evaluate the potential of chromosomal aberrations for the indirect assessment of prognosis in multiple myeloma patients. METHODS: We investigated the prevalence of cytogenetic aberrations in 41 patients with newly diagnosed multiple myeloma. Cytogenetic analysis was conducted by conventional karyotyping and FISH for the presence of IGH/CCND1 translocation, 13q14 deletion, and trisomy 1q using bone marrow aspirates. The records of routine laboratory tests were reviewed and their correlation with cytogenetic abnormalities was investigated. RESULTS: Sixteen (39.0%) of 41 patients had at least one cytogenetic abnormalities in conventional karyotyping or FISH. In FISH analysis of 37 patients, 8 (21.6%) showed positive result for IGH/CCND1 translocation, 8 (21.6%) for trisomy 1q, and 5 (13.5%) for 13q14 deletion. Cytogenetic abnormalities, especially trisomy 1q, were associated with significantly lower hemoglobin level and significantly higher bone marrow plasma cell percentage and beta2-microglobulin level. CONCLUSIONS: Statistical correlation between the presence of trisomy 1q and prognostic markers suggests that the evaluation of trisomy 1q in multiple myeloma patients may be used for the indirect assessment of prognosis in these patients.

Incidence and Histologic Patterns of Bone Marrow Involvement of Malignant Lymphoma Based on the World Health Organization Classification: A Single Institution Study / 대한진단검사의학회지

BACKGROUND: Working Formulation and Revised European American Classification of Lymphoid Neoplasms (REAL) have mainly been used in the studies for bone marrow involvement of malignant lymphoma in Korea. We investigated the incidence and histologic patterns of malignant lymphoma according to the WHO classification. METHODS: This study included 507 cases of malignant lymphoma that were requested for bone marrow study for the staging during the period January 1999-December 2005 in Korea Cancer Center Hospital. Medical records, peripheral blood smears, bone marrow aspiration smears, biopsy sections, and histopathologic findings were analyzed retrospectively. RESULTS: Of the 507 cases of malignant lymphoma, 473 (93.3%) were non-Hodgkin lymphoma (NHL) and 34 (6.7%) were Hodgkin lymphoma (HL). The overall incidence of bone marrow involvement by NHL and HL was 12.5% (59/473) and 11.8% (4/34), respectively. Among NHL cases, the incidence of bone marrow involvement by B-cell and T-cell neoplasms was 11.4% (43/377) and 16.7% (16/96), respectively. Although the incidences of bone marrow involvement by several B-cell neoplasms were more than 30%, diffuse large B cell lymphoma showed a relatively low incidence of bone marrow involvement (4.6%). Of bone marrow involvement patterns, diffuse infiltration pattern was the most common (40.0%). Peripheral blood involvement by lymphoma was observed in 35.6% of cases with bone marrow involvement. CONCLUSIONS: We used WHO classification in the study for the bone marrow involvement of malignant lymphoma, and this single-institution study should give a useful, up-to-date histopathologic information.

Influences of Genetic Polymorphisms of Glutathione S-transferase M1 and T1, and N-acetyltransferase 2 on Colorectal Cancer Risk / 대한진단검사의학회지

BACKGROUND: Inherited polymorphisms that affect carcinogen metabolism may influence the risk for the development of colorectal cancer. This study was performed to evaluate the potential association between glutathione S-transferase M1 (GSTM1), GSTT1 and N-acetyltransferase 2 (NAT2) polymorphisms and colorectal cancer in Korea. METHODS: The frequencies of GSTM1, GSTT1, and NAT2 polymorphisms were compared between 98 patients with colorectal cancer and age and sex matched 98 healthy controls. GSTM1 and GSTT1 polymorphisms were simultaneously determined by multiplex polymerase chain reaction (PCR) and NAT2 polymorphisms were analyzed by real-time PCR with melting curve analysis. GSTM1 null, GSTT1 null and NAT2 rapid type were considered as risk genotypes. RESULTS: The prevalence of GSTM1 null genotype was 44.9% in the controls, and 58.2% in the cases (odds ratio, OR=1.706, P=0.086). The prevalence of GSTT1 null genotype in the controls and the cases was 48.0% and 54.1%, respectively (OR=1.278, P=0.475). NAT2 rapid type were found in 45.9% of healthy controls and 51.0% of cancer patients (OR=1.227, P=0.568). Relative risk for colorectal cancer increased significantly (P=0.032) as the number of risk genotypes increased. CONCLUSIONS: These results suggest that genetic polymorphisms of GSTM1, GSTT1 and NAT2 have no independent effect on colorectal cancer risk individually, but there exists a dose-response relationship between a combined number of the risk genotypes of GSTM1, GSTT1 and NAT2 and colorectal cancer risk.