• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.3855-3859
• /
• 2016

Colorectal cancer (CRC) is reproted to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and disposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values p<0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5451-5454
• /
• 2012

Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

• Korean Journal of Biological Psychiatry
• /
• v.10 no.2
• /
• pp.177-185
• /
• 2003

Object:We investigated the relationship between prolactin response to antipsychotics and clinical courses of psychotic symptoms and DAT gene polymorphisms. Method:Twenty-four acute psychotic inpatients completed the 12-week trial of risperidone. Serum prolactin, BPRS, ESRS and hyperprolactinemia-related symptoms were measured at baseline, 2, 4, 8 and 12 weeks after medication. The DAT gene polymorphisms were analyzed. Results:The serum prolactin was significantly increased over time. According to the prolactin level at 2-week, the subjects were divided into the severe group(serum prolactin>60ng/mL, N=15) and the mild group (serum prolactin<60ng/mL, N=9). The prolactin levels of the mild group didn't increase beyond 60ng/mL throughout 12 weeks. Severe group had slower decrement of BPRS scores than those of mild group. Six females in severe group complained of irregular menstruations, but no female in mild group. Most patients had 10 allele of DAT gene. Conclusion:This study suggests that the magnitude of prolactin elevation at the 2-week of risperidone medication is correlated with severity of hyperprolactinemia throughout treatments. Our results did not show the relationship between prolactin responses and DAT gene polymorphisms.

• Korean Journal of Biological Psychiatry
• /
• v.16 no.3
• /
• pp.149-158
• /
• 2009

Objectives : This study was designed to investigate the association of schizophrenia and P1320, P1325, P1635, P1655, P1763 and SNP A polymorphisms on dystrobrevin binding protein 1(DTNBP1) gene in Korean patients. Methods : We analyzed P1320, P1325, P1635, P1655, P1763 and SNP A polymorphisms on DTNBP1 gene from their DNAs extracted from their blood in 388 Korean schizophrenic patients (male 198, female 190) and 372 control subjects(male 247, female 125). We compared the differences of genotype and allele distributions of the six polymorphisms on DTNBP1 gene between the Korean schizophrenic patient group and the normal control group. Results : There were no statistically significant differences of genotype and allele distributions of the P1320, P1325, P1635, P1655, P1763 and SNP A polymorphisms on DTNBP1 gene between the schizophrenic patient group and the normal control group. Conclusion : The results of this study suggest that P1320, P1325, P1635, P1655, P1763 and SNP A polymorphism on DTNBP1 gene do not have influence on the risk of the schizophnenic in the Korean population.

• Asian-Australasian Journal of Animal Sciences
• /
• v.26 no.6
• /
• pp.780-787
• /
• 2013

The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3431-3436
• /
• 2012

Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of the XRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusive results. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and the risk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons of the total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studies were included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from the current meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protective factors.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3417-3422
• /
• 2012

Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10255-10262
• /
• 2015

High risk human papillomavirus (HR-HPV) E2 proteins play roles in transcriptional regulation and are commonly functionally disrupted when the HPV genome integrates into host chromosomes. Some 15-40% of cancer cases, however, contain an intact E2 gene or episomal HPV. In these cases, polymorphism of the E2 gene might be involved. This study aimed to determine polymorphisms of the E2 gene in episomal HPV16 detected in high grade squamous intraepithelial lesions and squamous cell carcinomas and altered functions compared to the E2 prototype. The E2 gene was amplified and sequenced. Two expression vectors containing E2 gene polymorphisms were constructed and transfected in SiHa and C33A cells, then E6 gene as well as Il-10 and TNF-${\alpha}$ expression was determined by quantitative RT-PCR. Expression vectors and reporter vectors containing the HPV16 long control region (LCR) were co-transfected and transcriptional activity was determined. The results showed that a total of 32 nucleotides and 23 amino acids were changed in all 20 cases of study, found in the transactivation (TA) domain, hinge (H) region and DNA binding (DB) domain with 14, 5 and 13 nucleotide positions. They mostly caused amino acid change. The expressing vectors containing different E2 gene polymorphisms showed E6 mRNA suppression, TNF-${\alpha}$ mRNA suppression and IL-10 induction but no statistically significant differences when compared to the E2 prototype. Moreover, promoter activity in HPV16 LCR was not affected by E2 protein with different gene polymorphisms, in contrast to nucleotide variations in LCR that showed an effect on transcription activity. These results demonstrated that E2 gene polymorphisms of episomal HPV16 did not affect transcriptional regulation and suggested that nucleotide variation as well as epigenetic modification of the LCR might play a role in inducing malignant transformation of cells containing episomal HPV16.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2541-2545
• /
• 2012

Objective: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome of platinum-based chemotherapy in ovarian cancer patients. Methods: With a prospective study design was cases were consecutively collected from January 2005 to January 2007. All 310 included patients were followed-up until the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqMan Gene Expression assays. Results: A total of 191 patients died during follow-up. Our study showed a lower survival rate in XRCC1 399 Arg/Arg genotype than Gln/Gln, with a significant increased risk of death (HR=1.69, 95%CI=1.07-2.78). Similarly, those carrying XRCC3 Thr/Thr genotype had a increased risk as compare to the Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association between XRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. Conclusion: Our study demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival of ovarian cancer patients.

• Environmental Analysis Health and Toxicology
• /
• v.28
• /
• pp.12.1-12.5
• /
• 2013

Objectives The role of genetic polymorphisms of tumor necrosis factor-alpha (TNF-${\alpha}$) for lung cancer development was evaluated. Methods Genotypes of the TNF-${\alpha}$ polymorphisms, -1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, were determined in 616 lung cancer cases and 616 lung cancer-free controls. Results After adjusting for body mass index and smoking, each TNF-${\alpha}$ genotype or haplotype composed of five TNF-${\alpha}$ single nucleotide polymorphisms did not show an association with lung cancer risk (p>0.05). The statistical power was found to be 88.4%, 89.3%, 93.3%, 69.7%, and 93.9% for 1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, respectively. Furthermore, the effects of each SNP or haplotype on lung cancer risk were not found to be different according to the cell type of lung cancer (p>0.05). In the repeated analysis with only subjects without other diseases related to inflammation, there was also no association between polymorphisms or haplotypes of the TNF-${\alpha}$ gene and lung cancer risk (p>0.05). Conclusions This study found no association between common variants of the TNF-${\alpha}$ gene and lung cancer risk.