• Title/Summary/Keyword: CYP17A1 A1/A2 polymorphism

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Association of Benign Prostate Hyperplasia with Polymorphisms in VDR, CYP17, and SRD5A2 Genes among Lebanese Men

  • El Ezzi, Asmahan Ali;Zaidan, Wissam Rateeb;El-Saidi, Mohammed Ahmed;Al-Ahmadieh, Nabil;Mortenson, Jeffrey Benjamin;Kuddus, Ruhul Haque
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1255-1262
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    • 2014
  • Background: The aim of the study was to investigate any associations between benign prostate hyperplasia (BPH) and single nucleotide polymorphisms (SNPs) in the VDR gene (FokI, BsmI, ApaI and Taq${\alpha}$I loci) and the CYP17 gene (MspA1I locus), as well as TA repeat polymorphism in SRD5A2 gene among Lebanese men. Materials and Methods: DNA extracted from blood of 68 subjects with confirmed BPH and 79 age-matched controls was subjected to PCR/PCR-restriction fragment length polymorphism analysis. The odds ra=tio (OR) of having a genotype and the relative risk (RR) of developing BPH for having the genotype were calculated and the alleles were designated risk-bearing or protective. Results: Our data indicated that the A and B alleles of the VDR ApaI and BsmI SNPs were highly associated with increased risk of BPH (p=0.0168 and 0.0002, respectively). Moreover, 63% of the controls compared to 43% of the subjects with BPH were homozygous for none of the risk-bearing alleles (p=0.0123) whereas 60% of the controls and 28% of the subjects with BPH were homozygous for two or more protective alleles (p<0.0001). Conclusions: For the first time, our study demonstrated that ApaI and BsmI of the VDR gene are associated with risk of BPH among Lebanese men. Our study also indicated that overall polymorphism profile of all the genes involved in prostate physiology could be a better predictor of BPH risk.

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

  • Chong, Eric Tzyy Jiann;Goh, Lucky Poh Wah;See, Edwin Un Hean;Chuah, Jitt Aun;Chua, Kek Heng;Lee, Ping-Chin
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.647-653
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    • 2016
  • Background: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study. Materials and Methods: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population. Conclusions: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.

The Relationship between the Polymorphism of CYP1A1, GSTM1, GSTT1, GSTP1 and p53 Overexpression in Head and Neck Squamous Cell Carcinoma (두경부 편평세포암종에서 CYP1A1, GSTM1, GSTT1, GSTP1 유전자 다형성 및 p53 과발현)

  • Tae Kyung;Park Hye-Kyung;Lee Seung-Hwan;Kim Kyung-Rae;Lee Hyung-Seok
    • Korean Journal of Head & Neck Oncology
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    • v.19 no.2
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    • pp.148-157
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    • 2003
  • Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

Effect of IL-1 Polymorphisms, CYP2C19 Genotype and Antibiotic Resistance on Helicobacter pylori Eradication Comparing Between 10-day Sequential Therapy and 14-day Standard Triple Therapy with Four-Times-Daily-Dosing of Amoxicillin in Thailand: a Prospective Randomized Study

  • Phiphatpatthamaamphan, Kittichet;Vilaichone, Ratha-korn;Siramolpiwat, Sith;Tangaroonsanti, Anupong;Chonprasertsuk, Soonthorn;Bhanthumkomol, Patommatat;Pornthisarn, Bubpha;Mahachai, Varocha
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1903-1907
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    • 2016
  • Background: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. Materials and Methods: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Conclusions: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.