Analysis of CYP3A5*3 and CYP3A5*6 Gene Polymorphismsin Indian Chronic Myeloid Leukemia Patients

CYP3A5 is a member of the CYP3A gene family which metabolizes 50% of therapeutic drugs and steroidhormones. CYP3A5*3 and CYP3A5*6 polymorphisms exhibit inter-individual differences in CYP3A5 expression.The CYP3A5*3 allele (A6986G transition in intron 3) results in loss of CYP3A5 expression and the CYP3A5*6allele (G14690A transition in exon 2, leading to the skipping of exon 7) is associated with lower CYP3A5 catalyticactivity. The aim of the present study was to investigate their influence on susceptibility to chronic myeloidleukemia (CML). 265 CML cases and 241 age and sex matched healthy controls were analyzed by the PCR-RFLPtechnique. The frequencies of homozygous 3/3 genotype and CYP3A5*3 allele were elevated significantly in theCML group compared to controls (χ2=93.15, df=2, p=0.0001). With respect to clinical parameters, CYP3A5*3allele frequency was increased in patients with advanced phase of the disease (0.71) as compared to those inchronic phase (0.65). Patients without hematological response (minor/poor) had higher frequency of 3/3 genotype(54.54%) as compared to those with major hematological response (41.2%). CYP3A5*6 allele was not observed incases as well as in controls. Our study suggests that the CYP3A5*3 gene polymorphism is significantly associatedwith the risk of CML development and disease progression.     

Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia

Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acutemyeloid leukemia patients and identify any role in disease progression and outcome. Materials and Methods:DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP).Results: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34(41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and completeresponse (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overallsurvival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progressionfreesurvival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has norole in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival inacute myeloid leukemia patients.     

Association of SDF-1 Gene Polymorphism with Increased Risk of Acute Myeloid Leukemia Patients

Background: Acute myeloid leukemia (AML) is a heterogenous group of disorders that emerge from the malignant transformation of hematopoietic stem cells. Chemokine stromal cell-derived factor 1(SDF-1) and its receptor CXC receptor 4 (CXCR4) has an essential role in dissemination of blast cells. Study aimed to detect CXCR4 expression and the SDF-1 (rs1801157) gene polymorphisms and correlate them with prognosis and outcome in AML patients. Subjects and Methods: The study was conducted on 60 de-novo AML patients, and 60 healthy controls. SDF-1 (rs1801157) gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and CXCR4 expression was done using flow cytometry analysis. Results: SDF-1 dominant model (AG+AA) had higher risk AML (p 0.002). CXCR4positive cases were associated significantly with toxic manifestations (p 0.019), lower CR rates (p 0.004), and unfavorable cytogenetics (p 0.027). Multivariate analysis showed that combined CXCR4positive with dominant SDF-1 considered as independent prognostic factor for shorter overall survival (OS) in AML patients (p 0.031). Conclusion: SDF-1 dominant model had a higher risk to develop AML, and CXCR4 positive expression predicts poor prognosis in AML patients and it could represent a targeted therapy in AML. In addition, CXCR4 could be easily integrated into the initial routine diagnostic work up of AML.     

The Clinicopathological Impact of Granulocyte-Macrophage Colony-Stimulating Factor Gene Expression and Different Molecular Prognostic Biomarkers in Egyptian Acute Myeloid Leukemia Patients

Background: Acute myeloid leukemia (AML) is characterized by clonal expansion of myeloid precursors with diminished capacity for differentiation. It develops as the consequence of a series of genetic changes in a hematopoietic precursor cell. Purpose This study aimed to investigate the correlation between GM-CSF gene expression and different molecular prognostic markers such as FLT3-ITD, NPM1 mutation A and CEBPA gene expression in 100 Egyptian AML patients. As well as, correlation with the response to induction therapy, DFS andOS in these patients. Methodology: Quantitative assessment of GM-CSF gene expression was performed by qRT-PCR. Additional prognostic molecular markers were determined as FLT3-ITD and NPM1 mutation A together with quantitative assessment of CEBPA gene expression by qRT-PCR. Results: Patients with high GM-CSF expression levels had better OS and DFS with p value 0.004 and 0.02, respectively. However, no statistically significant difference between low andhigh GM-CSF gene expression was found regarding the response to therapy (p value= 0.08). Most patients with low CEBPA expression had resistant disease together with poor OS and DFS (P value =     

Association of CYP1A1 rs1048943 Polymorphism with Prostate Cancer in Iraqi Men Patients

Objective: The purpose of this study was to evaluate the relationship between CYP1A1 gene rs1048943 polymorphism and the risk of Iraqi men with prostate cancer. Methods: In this research, we conducted a population-based approach that intersects high-throughput genotype information from  different population of Iraq to estimate the frequency of genotypes associated with prostate cancer responsivenessOur study included a total of 100 patients and 150 healthy controls. rs1048943 genotyping has been investigated in Iraqi men in connection with prostate cancer. Results: We observed that individuals with the rs1048943 GA genotype had an increased risk of prostate cancer relative to those with the AA genotype  ( OR 95% CI of 0.449 :95%CI 0.23-0.90; P = 0.002). We found in the dominant model that the rs1048943 GA and GG genotype displayed an increased risk of prostate cancer relative to the AA genotype   ( OR 95% CI of 0.680 :95%CI 0.4-1.17; P = 0.018). Conclusion: Polymorphism RS 1048943 in the CYP1A1 gene is associated with the risk of developing prostate cancer and is possibly one of the most significant factors in its development.     

Association of CYP2C19 Polymorphisms with Survival of Breast Cancer Patients Using Tamoxifen: Results of a Metaanalysis

Background: Previous studies accessing the association of CYP2C19 with outcomes of patients using tamoxifenfor breast cancer have yielded conflicting results. The aim of this meta-analysis is to obtain a more precise estimateof effects of CYP2C19 polymorphisms and to clarify their effects on survival of the breast cancer patients usingtamoxifen. Materials and Methods: A systematic search of PubMed and Embase was performed, comparingpatients with or without CYP2C19*2 and CYP2C19*17, relevant articles searched for. The following outcomeswere included from the eligible studies: disease-free survival (DFS) and overall survival (OS), expressed byhazard ratios (HR) with corresponding 95% confidence interval (CI). Subgroup analysis by genotypes was alsoperformed. Pooled estimates were calculated using random-effect model in accordance to the heterogeneity.Results: Six studies met the inclusion criteria. The integrated OR on the association between CYP2C19 andDFS, calculated by the random-effect model, was 0.54 (95%CI=0.34-0.84, p=0.013). Subgroup analysis showedthat both CYP2C19*2 and CYP2C19*17 were associated with increased survival. The pooled results of twostudies for OS were OR=0.46 (95%CI=0.21-1.01, p=0.233). Conclusions: This meta-analysis suggests that theCYP2C19*2 and CYP2C19*17 genotypes are associated with increased survival in breast cancer patients usingtamoxifen.     

Association of an MDR1 Gene (C3435T) Polymorphism with Acute Leukemia in India

The multidrug resistance (MDR1) gene product P-glycoprotein is a membrane bound protein that functions as an ATP-dependent efflux pump, transporting exogenous and endogenous substrates from the cells. Since it plays an important role in chemotherapy, there is an increasing interest in the possible significance of genetic variation in MDR1. Our main objective was to study the MDR1gene polymorphism at C3435T with reference to development and progression of acute leukemia. The present study included 290 acute leukemia cases, comprising of 147 acute lymphocytic leukemia (ALL), 143 acute myeloid leukemia and 249 age-sex matched control samples for the analysis of MDR1 C3435T polymorphism, by the PCR-RFLP method. The MDR1 genotype distribution revealed an elevated frequency of the TT genotype in ALL cases (51.7%) as compared to controls (28.9%), whereas AML group did not show any association. The mean white blood cell count, blast% and LDH levels were increased in ALL patients with the CC genotype. No deviation was observed with respect to haemoglobin, platelet count and disease free survival in ALL patients. The association of CC genotype with clinical variables in ALL indicated that the CC genotype with high expression might be eliminating antileukemic drugs (anthracyclines, Daunorubicin, Vincristeine, Mitoxanthrone) which are P-gp substrates, leading to lower intra cellular drug concentrations and a poor prognosis. Such an association with the CC genotype was not observed in AML. In conclusion, these results suggested that the MDR1 TT genotype might influence risk of development of acute lympoblastic leukemia and the CC genotype might be linked to a poor prognosis of ALL.     

Prognostic Relevance of DNMT3A,FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients

Objective: Among all types of hematological neoplasms, acute myeloid leukemia (AML) has the highest death rate. Recently, cytogenetic and molecular genetics are crucial in the management, as a consequence of their effect on AML pathogenesis, classification, risk-stratification, prognosis and treatment. Methods: 100 Syrian adults with Normal Karyotype (NK) newly diagnosed  AML patients were included in this study, all cases confirmed histologically and immunohistochemically. Patients were divided into six subgroups using flow cytometry and cytological results. Polymerase chain reaction (PCR) was performed on exon 11-12 for FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), exon 12 for Nucleophosmin1 (NPM1), and exon 23 for DNA methyltransferase 3A (DNMT3A) using target primers, the electropherograms were analyzed for gene mutations by comparing with the reference DNA sequence. Data were compared and aligned with different sequences using the NCBI BLAST Assembled Genomes tool. Results: FLT3-ITD, NPM1 and DNMT3A were detected in 24%, 22 % and 4%  patients respectively. M2 subtype had the most frequent incidence of diagnosis in AML. FLT3-ITD mutation patients had the highest mean of death cases, while the DNMT3A mutation patients had the lowest. On the other hand, the highest mean of remission was in patients with NPM1 mutation and the lowest in the carriers of the FLT3-ITD mutation. It was observed that the mean relapsed patients with FLT3-ITD and DNMT3A mutation was 3.4 and 2 months respectively, with no significant differences between (FLT3-ITD and DNMT3A) carriers and non-carriers relapsed. On the contrary,  the mean relapsed for NPM1 mutation carriers was 2.4  months with significant statistical differences. The mean survival time for patients with FLT3-ITD and NPM1  mutation was 5.9 months and 5.85 months respectively, with significant correlation. Between it was 5.88 months in DNMT3A patients with no significant differences. Finally, It was noted that the mean event free survival (EFS) of FLT3-ITD mutation patients was 4.818 months and the mean EFS of NPM1 mutation patients was 4.805 months, with significant statistical differences (p<0.05) between the mutation patients and non-mutated patients regarding to EFS, While this mean was not statistically significant in patients carrying DNMT3A mutation. Conclusion: Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.     

Clinical Effect of Combined Mutations in DNMT3A,FLT3-ITD,and NPM1 Among Egyptian Acute Myeloid Leukemia Patients

BackgroundGenotypic mutation of fms like tyrosine kinase 3 (FLT3), Nucleophosmin (NPM1), and DNA-methyltransferase 3A (DNMT3A) has been involved in the leukemogenesis of acute myeloid leukemia (AML), with the well known poor prognostic role of FLT3 and DNMT3A and favorable role for the NPM1 mutation.Patients and MethodsA total of 123 patients with AML treated at the National Cancer Institute, Cairo University were examined for mutations in DNMT3A, FLT3, and NPM1 using polymerase chain reaction (PCR) for detecting FLT3 internal tandem duplication (ITD) and allele-specific PCR to detect DNMT3A and NPM1A mutations. Two-way direct sequencing and Gene Mapper version 4.0 software (Fred Hutchinson Cancer Research Center) sequencing were used as confirmatory tests for DNMT3A and NPM1A mutations, respectively.ResultsDNMT3A, FLT3-ITD, and NPM1A gene mutations were detected in 22 (17.9%), 22 (17.9%), and 24 (19.5%) patients, respectively. DNMT3A/FLT3, NPM1A/FLT3, and DNMT3A/NPM1A combined mutant genotypes were detected in 5 (4.1%), 9 (7.3%), and 3 (2.4%) patients, respectively. Two patients (1.6%) had triple mutant genotypes (DNMT3A/FLT3/NPM1A). FLT3 and DNMT3A mutations had a significant negative effect on complete response (CR) rates (P = .016). FLT3-ITD mutation was significantly associated with older age (P = .029), and lower overall survival (OS) rates (P = .046). DNMT3A/FLT3 combined mutant genotypes were significantly associated with a lower OS rate (P = .016). Mutant NPM1/wild type FLT3, wild type DNMT3A/FLT3, and mutant NPM1A/wild type DNMT3A combinations were significantly associated with higher CR rates (P = .006, P = .006, and P = .023, respectively).ConclusionDNMT3A, FLT3-ITD, and NPM1A are frequent mutations in Egyptian AML. FLT3-ITD mutations are frequent in older patients. DNMT3A and FLT3-ITD mutations were associated with an unfavorable prognosis, but the NPM1A mutation has tendency to indicate a good prognosis.     

NOTCH-1 Gene Mutations Influence Survival in Acute Myeloid Leukemia Patients

Background: Although NOTCH-1 gene mutations were reported to contributes to leukemogenesis in lymphocytic leukemias, its role in acute myeloid leukemia (AML) remains unclear. Therefor; this study was designed to determine the prevalence and clinical impact of NOTCH-1 mutations in AML patients. Materials and Methods: In the current study, NOTCH-1 gene mutations were identified in Bone Marrow samples obtained from fifty primary AML patients before start of therapy using Sanger sequencing. Results: NOTCH-1 gene mutations were detected in 6 out of 50 AML cases (12%). The three mutations were (two mutations C7318A in the Pest domain exon 34); (another 2 in the Pest domain Del 7,344, ins C7349, G7356A and the last ones in the HD-N exon-26 (Del A4609). The clinical findings in the mutant AML (mu AML) patients did not significantly different as compared to the un mutated (unmut) AML patients.  There is significant association between CD7 aberrant expression and NOTCH-1 mutations. The complete remission was significantly higher in unmut AML cases as compared to mut AML ones (P=0.024). Multivariate (Age; Gender; Bone Marrow Blast cells; NOTCH-1 mutations) Cox regression analysis revealed that NOTCH-1 mutation is an independent risk factor for AML overall survival (P<0.001). The OS in unmut AML group (21.2 months) was significantly longer as compared to mut AML one (1.2 months) (P<0.001). Conclusion: Our data indicate that NOTCH-1 gene mutations were detected in 12% of AML patients. These mutations displayed bad clinical outcome on AML patients. Therapeutic targeting of NOTCH-1 could be a potentially effective approach to combat master oncogenic drivers in AML.     

CYPlAl和CYPlA2基因多态性与汉族女性乳腺癌的关系

目的 探讨CYP1A1基因MspⅠ位点与CYP1A2基因C734A位点多态性与汉族女性乳腺癌的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术和限制性核酸内切酶酶切的方法,检测2011年9月至2012年8月在四川省医学科学院四川省人民医院确诊的144例女性乳腺癌患者（乳腺癌组）和152例同期健康体检正常女性（对照组）CYP1A1基因MspⅠ与CYP1A2基因C734A多态性位点的基因型,用χ2检验比较两组等位基因频率的差异.结果 在乳腺癌组与对照组中,CYP1A1基因MspⅠ位点T等位基因频率分别为0.73和0.65,两者差异有统计学意义（χ2=4.94,P=0.03）,C等位基因与T等位基因相比,乳腺癌发病风险OR为0.67 （95%CI：0.47～0.96）;CYP1A2基因C734A位点C等位基因频率分别为0.26和0.29,两者差异无统计学意义 （χ2=0.63,P=0.43）.将乳腺癌组按照ER、PR表达与否进一步分组后,CYP1A1基因MspⅠ与CYP1A 2基因C734A 2个多态性位点的等位基因频率在ER（＋）与ER（-）组之间以及PR（＋）与PR（-）组之间差异均无统计学意义[ER（＋）组比ER（-）组：χ2=0.34、0.01;PR（＋）组比PR（-）组：χ2=0.60、0.68;P均〉0.05].结论 汉族女性CYP1A1基因MspⅠ位点多态性与乳腺癌相关联.     

CYP3A5*3基因多态性与晚期非小细胞肺癌患者应用多西他赛的疗效及安全性分析

目的:研究CYP3A5*3基因多态性对应用多西他赛治疗的晚期非小细胞肺癌患者的疗效以及安全性的相关性分析。方法:通过多基因检测技术明确患者CYP3A5*3的基因多态性状态，通过查阅随访表、病理以及随访电话明确患者的基本信息，包括性别、年龄、是否吸烟、EGFR状态和ECOG评分等，明确生存信息，即无进展生存期（PFS）和总生存期（OS）。通过不良反应表统计不良反应发生情况。用卡方检验对基因多态性与患者的不良反应进行相关性分析，用Kaplan-Meier生存曲线分析基因多态性与患者的PFS和OS的关系。结果:在生存分析方面，CYP3A5*3纯合突变型患者的中位总生存期约26个月，高于杂合型的24个月和野生型的22个月（P=0.833）。CYP3A5*3纯合突变型患者的中位无进展生存期4个月，也高于杂合型的2个月和野生型的3个月（P=0.306）。在不良反应方面，共有11例患者发生Ⅲ级以上骨髓抑制，其中7例（63.6%）患者为CYP3A5*3纯合突变型，考虑该基因型发生中重度骨髓抑制的可能性更大（P=0.415）。此外，有6例患者发生皮疹，其中5例（83.3%）为CYP3A5*3纯合突变型，还包括1例Ⅲ度皮疹。考虑该基因型患者发生皮疹的可能性更大（P=0.490）。手足综合征、神经毒性、肾毒性以及口腔黏膜炎等仅发生在 CYP3A5*3野生型及CYP3A5*3纯合突变型患者中。结论:应用多西他赛的晚期非小细胞肺癌患者中，CYP3A5*3纯合突变型患者的生存期高于杂合型和野生型患者。CYP3A5*3纯合突变型患者发生中重度骨髓抑制、皮疹的风险可能性更大。     

CYP1A1*2A基因多态性与宁夏汉族乳腺癌遗传易感性研究

[目的]分析宁夏汉族CYP1A1＊2A基因多态性与乳腺癌遗传易感性的关系。[方法]应用聚合酶链反应—限制性片段长度多态性（PCR-RFLP）技术分别对144例乳腺癌患者和154例对照的CYP1A1＊2A基因多态性进行测定,分析两组基因型及等位基因频率的分布特点。[结果]CYP1A1＊2A等位基因T、C在乳腺癌组和对照组分布的差异无显著性（P〉0.05）,其中等位基因C的乳腺癌发病风险比值比（OR）为1.34（95%CI：0.97～1.86）。CYP1A1＊2A各基因型分布两组间差异也无显著性（P〉0.05）,杂合子突变TC、纯合子突变CC分别与野生型TT相比,乳腺癌发病风险OR分别为1.32（95%CI：0.80～2.18）和1.86（95%CI：0.92～3.78）。[结论]CYP1A1＊2A基因多态性其突变纯合子和杂合子有增加乳腺癌风险的趋势,但未达到显著水平。CYP1A1＊2A基因多态性可能与宁夏汉族人群乳腺癌的发病有关系。     

Association of an LMP2 Polymorphism with Acute Myeloid Leukemia and Multiple Myeloma

Hematological malignancies (HM) are a group of neoplasms derived from the cells of the bone marrowand lymphatic system. Genetic factors leading to susceptibility to HM have been investigated for years butlittle is known yet. Low molecular weight polypeptide (LMP) 2 and LMP7 genes are important subunits of theimmunoproteasome and play significant role in antigen presentation. The polymorphisms of LMP genes have beenreported to be risk factors for various types of diseases. The aim of this study was to investigate the associationof LMP2 and LMP7 polymorphisms with the occurrence of particular types of HM. A total of 132 patients withHM and 130 control subjects were investigated. No significant difference was obtained in the distribution ofgenotype and allele frequencies of LMP7 gene in HM patients and the control group. On the other hand, theprevalence of LMP2-AA genotype was found to be higher in acute myeolid leukemia (AML) patients while itwas significantly lower in multiple myeloma (MM) cases than in the control subjects. Our results suggested thatLMP7 could not be a risk factor for susceptibility to HM, whereas LMP2 polymorphisms could play a role inthe development of AML and MM.     

索拉非尼靶向治疗FLT3-ITD阳性急性髓系白血病

FMS样酪氨酸激酶-3（FLT3）近膜区的的内部串联重复序列（FLT3 internal tandem duplications, FLT3/ITD）突变是急性髓系白血病中常见的基因突变类型,与急性髓系白血病（acute myeloid leukemia, AML）的发生发展及不良预后有密切关系。目前多靶点酪氨酸激酶抑制剂药物的研究成为近几年来治疗FLT3/ITD阳性AML研究的热点,尤其是对多靶点抑制剂索拉非尼（sorafenib）的研究较为深入。本文通过学习国内外相关文献资料,综述酪氨酸激酶抑制剂索拉非尼在治疗FLT3/ITD 阳性AML的疗效和作用机制方面的研究进展。     

Implications of Glutathione Peroxidase 3 Expression in a Cohort of Egyptian Patients with Acute Myeloid Leukemia

Background: The impact of low expression of Glutathione peroxidase 3 (GPX3) on the clinical course of acute myeloid leukemia (AML) is poorly investigated. Aims: To explore the status of GPX3 expression and analyze its clinical characteristics and prognosis in a cohort of Egyptian patients with AML. Methods: GPX3 mRNA level was assessed by RT-q PCR in 40 newly diagnosed AML patients and 10 healthy controls. Results: The gene expression level was significantly lower in AML patients than the control group (P < 0.001). A cut off value (0.1223) for the discrimination between AML and controls was obtained by ROC curve. According to this cutoff value; the patients were reassigned into 2 groups; 28 patients with lower GPX3 expression and 12 patients with high GPX3 expression. GPX3low expression was significantly associated with higher incidence of induction death (P= 0.037) and lower CR rate (P=0.048). Moreover, GPX3low expression was significantly associated with shorter cumulative 1-year overall survival (OS) (P = 0.001) and disease-free survival (DFS) (P=0.028). Conclusion: GPX3low expression status is considered a poor prognostic factor in AML predicting shorter OS and DFS. The study highlights the importance of targeting glutathione metabolism as a central component of the anti-leukemia therapy.     

Meta-analysis of the CYP1A2 -163C>A Polymorphism and Lung Cancer Risk

Many published studies have concerned associations between the CYP1A2 -163 C>A polymorphism and riskof lung cancer, but the results have been inconsistent. Therefore, we performed a meta-analysis to obtain a moreprecise estimate. We searched the PubMed database up to March 1, 2013 for relevant cohort and case-controlstudies. Supplementary search was conducted manually by searching the references of the included studies andrelevant meta-analyses. A meta-analysis was performed using RevMan 5.2 software for calculation of pooledodds ratios (ORs) and relevant 95% confidence intervals (CIs) after data extraction. Finally, seven case-controlstudies and one nested case-control study involving 1,675 lung cancer patients and 2,393 controls were included.The meta-analysis showed that there was no association of CYP1A2 -163 C>A polymorphism with risk of lungcancer overall [(OR=0.89, 95%CI= 0.74-1.07) for C vs. A; (OR=0.73, 95%CI= 0.50-1.07) for AA vs. CC ; (OR=0.82,95%CI= 0.62-1.09) for AC vs. CC; (OR=0.79, 95%CI= 0.58-1.07) for (AC+AA) vs. CC; and (OR=0.87, 95%CI=0.67-1.13) for AA vs. (CC+AC)]. Subgroup analysis indicated that there was an associationbetween CYP1A2-163C>A polymorphism and lung cancer risk for population-based controls, a trend risk for SCCL (squamouscell carcinoma of lung) and Caucasians. These results suggested that -163 C>A polymorphism is likely to beassociated with risk of lung cancer compared with population-based controls.