• Genomics & Informatics
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• 제8권1호
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• pp.1-8
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• 2010

Serpin peptidase inhibitor, Clade B (ovalbumin), Member 5 (SERPINB5), also known as maspin, is a potent tumor suppressor gene. It has correlations with many tumor cells, from pancreas cancer to breast cancer, so it is possible that it may also affect liver cancer. There has also been a report that SERPINB12, a gene placed right next to SERPINB5, is expressed in liver. For this study, 32 polymorphisms were identified in SERPINB5 by direct DNA sequencing, and 11 of them were selected to be tested with a larger scale subjects. The association of the 11 SERPINB5 polymorphisms with Hepatitis B virus (HBV) clearance, hepatocellular carcinoma (HCC) occurrence and the onset age of HCC were analyzed. There were no significant associations found between 11 SERPINB5 polymorphisms and HBV clearance. In the case of HCC occurrence, one of the haplotypes (ht) showed association with HCC occurrence (OR=2.26, p=0.005, $P^{Cor}=0.05$), albeit with a low statistical power (40.8%) and haplotype frequency (0.052). Further study with a bigger sample size will be needed to clearly verify the association between ht5 and HCC occurrence.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8775-8778
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• 2014

Background: To explore the relationship between polymorphisms of interleukin17 (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor for lung cancer. Materials and Methods: A total of 113 silicosis patients and 116 workers without silicosis were enrolled in the case-control study. IL-17A A-832G and IL-17F 7488A/G polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of AA,GG and AG of IL-17A A-832G locus in the case and control groups were 46.9%, 8.0%, 45.1%, and 49.2%, 7.6%, 43.2%, respectively, with no significant differences (p>0.05).The GG genotype in the IL-17F (7488A/G) locus was not found. The frequencies of AA and GA of IL-17F 7488A/G locus in the case and control groups were 84.1%, 15.9% and 66.4%, 33.6%, respectively (p<0.05). Analysis of combined effects showed that the individuals with GG+AG genotype of IL-17A and GG+GA genotype of IL-17F are protected against silicosis (OR=0.469). Conclusions: IL-17F 7488A/G is associated with susceptibility to silicosis, and G allele may have a protective effect. No relationship was found between IL-17A gene polymorphisms at A-832G and silicosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5839-5842
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• 2013

Aim: We assessed the association between genetic variants of XPG, XPA, XPD, CSB, XPC and CCNH in the nucleotide excision repair (NER) pathway and risk of prostate cancer. Methods: We genotyped the XPG, XPA, XPD, CSB, XPC and CCNH polymorphisms by a 384-well plate format on the MassARRAY(R) platform. Multivariate logistical regression analysis was used to assess the associations between the six gene polymorphisms and risk of prostate cancer. Results: Individuals carrying the XPG rs229614 TT (OR=2.01, 95%CI=1.35-3.27) genotype and T allele (OR=1.73, 95%CI=1.37-2.57) were moderately significantly associated with a higher risk of prostate cancer. Subjects with XPD rs13181 G allele had a marginally increased risk of prostate cancer, with adjusted OR(95%CI) of 1.53 (1.04-2.37). Moreover, individuals carrying with CSB rs2228526 GG genotype (OR=2.05, 95% CI=1.23-3.52) and G allele (OR=1.56, 95%CI=1.17-2.05) were associated with a higher increased risk of prostate cancer. The combination genotype of XPG rs2296147 T and CSB rs2228526 G allele had accumulative effect on the risk of this cancer, with an OR (95% CI) of 2.23(1.37-3.59). Conclusions: Our study indicates that XPG rs2296147 and CSB rs2228526 polymorphisms are significantly associated with increased risk of prostate cancer, and that combination of XPG rs2296147 T allele and CSB rs2228526 G allele is strongly associated with an increased risk.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4739-4742
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• 2013

Carboplatin, a second generation platinum drug, is widely used to treat different types of cancers. However, myelosuppression remains a major consideration in its use. Genetic polymorphisms of enzymes involved in drug disposition can influence therapeutic outcome. The homozygous null deletion of phase II metabolic gene GSTT1 that abolishes its xenobiotic- detoxifying ability may be associated with carboplatin toxicity. Further, since carboplatin generates oxidative stress, polymorphisms of oxidative stress genes that regulate the cellular level of free radicals may have important roles in generating drug- related adverse effects. We here investigated the null polymorphism of GSTT1, and the -463G>A promoter polymorphism of oxidative stress gene myeloperoxidase (MPO) for carboplatin toxicity in a population of northern India. Cancer patients who were treated with carboplatin, and developed toxicity was considered. The study group comprised of 10 patients who developed therapy- related adverse effects. Peripheral blood was taken from patients for DNA isolation. GSTT1 null genotype was determined by conducting duplex PCR and MPO-463 G>A was determined by PCR followed by RFLP. Hematologic toxicity was experienced by 5 patients, 2 of them had grade 3 and 4 toxicity and 3 others had grade 2 toxicity. They also had gastrointestinal (GI) toxicity. Remaining 5 individuals developed GI toxicity but no hematological toxicity. While GG homozygous of MPO was present in majority of patients having hematologic toxicity (in 4 out of 5 individuals), one A allele (AG genotype) was present in 4 patients who did not have any hematological toxicity. Thus variant A allele of MPO -463G>A may be related to lower hematological toxicity. These preliminary data, however, are required to be confirmed in larger studies along with other relevant polymorphisms.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1247-1250
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• 2015

Background: Psoriasis, a common cutaneous disorder characterized by inflammation and abnormal epidermal proliferation with a prevalence of 2-3% in the general population, may be linked to certain types of cancer. Several studies have reported an association between interleukin 10 (IL-10) variant polymorphisms and inflammatory diseases such as psoriasis vulgaris although the results vary according to the population studied. No studies have been performed in the Saudi population. The present study concerned novel variants and other genetic polymorphisms of the promoter and exonic regions of the IL10 gene in patients with moderate to severe psoriasis and potential differences in genotype compared to a group of healthy volunteers. Materials and Methods: Patients with moderate to severe psoriasis and healthy controls with no personal or family history of psoriasis were selected from the central region of Saudi Arabia. Polymorphisms of the IL 10 gene of both groups were genotyped. Results: We observed two novel variants in 5'UTR region of the promoter precursor with higher prevalence of the genotype with both wild-type alleles in patients compared to the healthy control group. The differences at positions -377 and -150 were significantly associated with disease, both the variants conferred strong protection against psoriasis in Saudi patients. Conclusions: This observation provides further support for the importance of the part that IL10 plays in the pathophysiology of this disease. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of IL-10 in psoriasis.

• Genomics & Informatics
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• 제16권4호
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• pp.38.1-38.3
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• 2018

Gene-gene interaction (GGI) analysis is known to play an important role in explaining missing heritability. Many previous studies have already proposed software to analyze GGI, but most methods focus on a binary phenotype in a case-control design. In this study, we developed "Hierarchical structural CoMponent analysis of Gene-Gene Interactions" (HisCoM-GGI) software for GGI analysis with a continuous phenotype. The HisCoM-GGI method considers hierarchical structural relationships between genes and single nucleotide polymorphisms (SNPs), enabling both gene-level and SNP-level interaction analysis in a single model. Furthermore, this software accepts various types of genomic data and supports data management and multithreading to improve the efficiency of genome-wide association study data analysis. We expect that HisCoM-GGI software will provide advanced accessibility to researchers in genetic interaction studies and a more effective way to understand biological mechanisms of complex diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2439-2442
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• 2013

We investigated the possible association of interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia (AML) in 115 patients and 137 healthy controls. Genetic analysis of IL-10 SNPs at -819 and -592 was carried out with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The IL-10 mRNA expression of AML patients and controls with different genotype was detected by real-time quantitative polymerase chain reaction (RT-PCR). Genetic analysis of IL-10 revealed that the -819AA genotype frequencies and the -819A allele frequencies in the AML group were higher than in the controls (59.1% vs 40.9%; 75.6% vs 63.9%, respectively); there were remarkable differences in -819T/C and -592A/C gene distribution (P<0.05) and the TA haploid frequencies were higher in the AML group (75.6% vs 63.9%, P<0.05). IL-10 mRNA expression in incipient AML patients was obvious higher than the non-tumor group and the remission group ($7.78{\times}10^{-3}$ vs $2.43{\times}10^{-3}$, $3.64{\times}10^{-3}$, P<0.05).The study suggested that the haploid TA and genotype TA/TA may be associated with AML in Han people in Hunan province.The IL-10 SNPs at -819 and -592 sites were associated with AML and may affect IL-10 mRNA expression in AML patients.

• 한국콘텐츠학회논문지
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• 제17권10호
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• pp.289-299
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• 2017

아시아인종에서 만성골수성백혈병 (Chronic myeloid leukemia; CML)과 Glutathione S-transferase(GST) 유전자 다형성과 관련된 감수성을 검증하기 위해, 2017년 7월까지 발표된 9편의 논문들을 메타분석에 인용하였다. GST 유전자 다형성의 아형 중 M1 (GSTM1)과 T1 (GSTT1)의 유전자의 null, present 유형을 개별적으로 분석하였다. CML환자와 GST 유전자 다형성 사이에 연관성이 발견되었다.(GSTM1; OR=1.306, 95% CI=1.091-1.563, p=0.004, GSTT1; OR=1.987, 95% CI=1.438-2.746, p=0.000). 또한, CML 환자와 GSTM1-GSTT1 유전자 다형성 조합 null 유형의 연관성이 있었다(OR=4.191, 95% CI=2.833-6.201, p=0.000). 이와 같이, 아시아인종에서 GSTM1 유전자 다형성, GSTT1 유전자 다형성, GSTM1-GSTT1 유전자 다형성 조합은 CML 환자의 위험인자가 될 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6961-6967
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• 2014

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-${\gamma}$-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7741-7746
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• 2014

Although a number of studies have been conducted on the association between GSTM1 polymorphisms and lung cancer in China, this association remains elusive and controversial. To clarify the effects of GSTM1 polymorphisms on the risk of lung cancer, a meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to 5th April 2014. A total of 45 articles (47 studies) including 6,623 cases and 7,865 controls were involved in this meta-analysis. Overall, a significant association (OR = 1.45, 95%CI: 1.32-1.60) was found between the null GSTM1 and lung cancer risk when all studies in Chinese population pooled into the meta-analysis. In subgroup analyses stratified by quality score, geographic area and source of controls, the same results were observed under all the models. This meta-analysis showed that the null GSTM1 may be a potential biomarker for lung cancer risk in Chinese, but further studies with gene-gene and gene-environment interactions are required for definite conclusions.