• Journal of Preventive Medicine and Public Health
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• 제31권1호
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• pp.1-14
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• 1998

The genetically determined CYP2D6 activity as considered to be associated with cancer susceptibility with inter-individual variation. Genetic polymorphism of CYP2D6(B) and CYP2D6(T) was determined by the two polymerase chain reaction(PCR) and BstN1 and EcoN1 restriction fragment length polymorphisms(RFLP) for 67 lung cancer cases and 95 healthy volunteer controls. The cases were composed of 26 squamous cell carcinoma, 14 small cell carcinoma, 10 adenocarcinoma, 3 large cell undifferentiated carcinoma, and 14 not histologically diagnosed. The results were gained from the 142 subjects (57 cases and 85 controls) who observed successfully in two PCR and BstNl/EcoN1 RELP. Only one and no mutant allele of the CYP2D6(B) and CYP2D6(T) gene was detected, that is, the frequency of mutant allele was very low; 0.7%(1/142) and 0%(0/142), respectively. Detected mutant allele of the CYP2D6(B) was beterozygous type(WM). The odds ratios for lung cancer susceptibility with CYP2D6(B) and CYP2D6(T) genotype were not calculated. These results are similar to the previous understanding that the mutant allele is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6(B) and CYP2D6(T) genotypes have maybe no association with lung cancer susceptibility in Koreans. This is the basic data of CYP2D6(B) and CYP2D6(T) genotypes for Koreans. It would be hepful for further study to determine lung cancer susceptibility of Koreans with the data about CYP1A1, CYP2E1, GSTM1 from future study.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5557-5563
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• 2015

Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. Materials and Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched control subjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. Results: The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone (OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4583-4587
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• 2015

Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid 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 CYP2B6 G15631T 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 in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression-free survival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3761-3768
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• 2013

Background: The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. Materials and Methods: Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. Results and Conclusions: $CYP2E1^*6$ was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with $CYP1Awt/^*2A$ (odd ratio=3.65; 95% confidence interval 1.39-9.57). The $GSTM1^*0/^*0$ genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2647-2653
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• 2012

Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real-time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1145-1150
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• 2015

Associations of GSTT1, GSTM1 and CYP1A1 gene variants with risk of developing oral cancer were evaluated in this study. A case-control study was conducted in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 200 hospital based oral cancer cases and 151 population based healthy controls exposed to similar environmental conditions were included. Sociodemographic data were obtained and blood samples were collected with informed consent for analysis. GSTM1 and GSTT1 were analysed through conventional PCR method while specific RT-PCR method was used to detect CYP1A1 polymorphisms. Results were analyzed for conditional logistic regression model by SPSS version 20. The study shows that patients with either GSTM1 or GSTT1 null genotypes have significantly higher risk of oral cancer (adjusted odds (OR): (3.019 (1.861-4.898) and 3.011(1.865-4.862), respectively), which further increased when either one or both null genes were present in combination (adjusted odds (OR): (3.627 (1.981-6.642 and 9.261 (4.495-19.079), respectively). CYP1A1 rs4646903 gene variants individually showed weak association OR: 1.121 (0.717-1.752); however, in the presence of GSTM1 and/or GSTT1 null genotypes further increasing the association (adjusted odds (ORs): 4.576 (2.038-10.273), 5.593 (2.530-12.362) and 16.10 (3.854-67.260 for GSTM/GSTT null and CYP1A1 wild type, GSTM/GSTT either null and CYP1A1 variant alleles, and all 3 gene polymorphisms combinations, respectively). Our findings suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 may be the risk alleles for oral cancer susceptibility in Pashtun population.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6783-6787
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• 2015

Background: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer. Materials and Methods: A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3. Results: The mean age of the patients with the disease recurrence was $50.8{\pm}6.4$ and in non recurrent patients was $48.2{\pm}6.8$. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen-treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence. Conclusions: This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.

• 생명과학회지
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• 제28권2호
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• pp.176-186
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• 2018

김(Porphyra yezoensis, Laver)의 MeOH 추출에 의한 유기용매 별 분획물에서 폴리페놀 함량과 항산화 활성 및 간암세포주 HepG2의 세포증식 억제효과를 확인하였다. $CHCl_3$ 분획물의 폴리페놀 함량은 $10.34{\mu}g/mg$으로 물 분획물의 $13.08{\mu}g/mg$ 보다는 다소 적게 나타났으나, DPPH 자유라디칼 소거에 의한 전자공여능(EDA)에서 나타난 $ED_{50}$은 $16.96{\mu}g/ml$로 가장 높게 나타났다. $CHCl_3$과 EtOAc 분획물은 농도의존적으로 HepG2 세포의 증식을 억제하였으며, 특히 $900{\mu}g/ml$의 $CHCl_3$ 분획물을 24시간 동안 처리하여 90%의 세포증식이 억제되었다. 한편 $CHCl_3$ 분획물이 처리된 HepG2 세포의 유전자 발현 양상을 microarray로 확인하였다. P. yezoensis의 효능과 연관지은 gene ontology 분석으로 비타민 D 합성 과정, 항균작용에 대한 반응 및 영양물질에 대한 반응에 관련된 유의 유전자들을 탐색하였다. 유의 유전자로 IL6R와 CYP1A1를 선정하였고, 이들 유전자의 상위 조절자는 ARNT 유전자가 선정되었다. 또한 50 및 $100{\mu}g/ml$의 $CHCl_3$ 분획물이 처리된 HepG2 세포에서 IL6R와 CYP1A1 단백질의 발현과 상위 조절자인 ARNT의 활성을 Western blotting으로 확인하였다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.238.2-239
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• 2003

The purposes of this study were to evaluate the relationship between the genetic polymorphisms in CYP2D6*10 allele, MDR1 (exon 21 and 26) gene and risperidone pharmacokinetics in healthy male Korean subjects. A single dose of 2 mg risperidone tablet was given orally to 23 healthy male Korean volunteers. Blood samples were taken during the 12 hours after the dose. Serum concentrations of risperidone and 9-hydroxyrisperidone were measured using HPLC with UV detector. 23 subjects were genotyped for CYP2D6*10 allele, MDR1 G2677 T and C3435T by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). (omitted)

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.71-75
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• 2016

Pancreatic cancer is a leading cause of fatality worldwide. Several population studies have been conducted on genetic diagnosis of pancreatic cancer but the results from epidemiologic studies are very limited. CYP17A gene has a role in disease formation but its influence on pancreatic cancer is unclear. A polymorphism in the 5'UTR promoter region of CYP17A1-34T/C (A1/A2) has been associated with multiple cancers. The aim of the current study was to assess associations of this polymorphism and socio-demographic risk factors with pancreatic cancer. A total of 255 and 320 controls were enrolled in the study, and were genetically analyzed through PCR-RFLP. Statistical analysis was conducted with observed genotype frequencies and odds ratios (ORs) and 95% CIs were estimated using unconditional logistic regression. The impact of socio-demographic factors was accessed through Kaplen-Meir analysis. According to our results, the A2/A2 genotype was significantly associated with pancreatic cancer (OR=2.1, 95%CI = 1.3-3.5). Gender female (OR=2.6, 95%CI=1.8-3.7), age group 80s/80+ years (OR=2.2, 95% CI=1.2-4), smoking both former (OR=4.6, 95% CIs=2.5-8.8) and current (OR=3.6, 95% CI=2-6.7), and family history (OR=7.1; 95%CI = 4.6-11.4) were also found associated with increased risk. Current study suggests that along with established risk factors for pancreatic cancer CYP17A1-34T/C may play a role. However, on the basis of small sample size the argument cannot be fully endorsed and larger scale studies are recommended.