• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.3971-3977
• /
• 2016

Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

• Parasites, Hosts and Diseases
• /
• v.34 no.2
• /
• pp.127-134
• /
• 1996

Twelve isolates of Accnthamoebc app. assigned to either A. castellanii or A. poIMphoSa, and type strains of A. culbefsoni, A. henIWi, A. pqkestinefiE, and A. astronyxi,s were examined by restriction fragment length polymorphism (RFLP) of a conserved region of small subunit ribosomal RMh gene (ssu rDNA) amplified by polymerase chain reaction (PCR). The PCR products of the isolates measured approximately 910-930 bp, except for that of A. astronyxis which was extraordinarily long, approximately 1,170 bp. Average of estimated sequence divergence of the amplified DNA among the isolates assigned to A. castellanii was 9.8% whereas that among the isolates assigned to A. polvphusn 9.6%. The maximum intraspecific sequence divergence among the isolates assigned to A. costellanii was observed between the Chang and Ma strains (17.3%) while that among the isolates assigned to A. poIWphosa was observed between KA/S3 and KA/S7 strains (16.1%). The both maximum sequence divergences were much greater than the minimum interspecific sequence divergence between A. cnstellnnii and A. polwphasa (2.6%) which appeared between the Castellani (or CCAP 1501/12 g) and KA/S3 strains. The PCR-RFLP patterns of A. culbertsoni, A. healyi, A. palestinensis, and A. ostronvxis were quite diverse from one another and from those of isolates assigned to either A. castellanii or A. polyphoga. It is suggested that taxonomic validity of the isolates assigned to either A. castellnnii or A. polyphoga should be reevaluated.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6783-6787
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.11
• /
• pp.6427-6431
• /
• 2013

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world and deeply threatens people's health, especially in China. Techniques of early diagnosis, prevention and prediction are still being discovered, among which the approaches based on single nucleotide polymorphisms in microRNA genes (miRNA SNPs) are newly proposed and show prospective potential. In particular, the association between SNPs in miRNA196a-2 (rs11614913) and miRNA146a (rs2910164) and HCC has been investigated. However, the conclusions made were conflicting, possibly due to insufficient sample size or population stratification. Further confirmations in well-designed large samples are still required. In this study, we verified the association between these two SNPs and the susceptibility to HCC by MassARRAY assay in a 2,000 large Chinese case-control sample. Significant association between rs11614913 and HCC was confirmed. Subjects with the genotype of CT+TT or T allele in rs11614913 were more resistant to HCC (CT+TT: OR (95% CI)=0.73 (0.57-0.92), P=0.01; T allele: OR (95% CI)=0.85 (0.75-0.97), P=0.02) and HBV-related HCC (CT+TT: OR (95% CI)=0.69 (0.53-0.90), P=0.01; T allele: OR (95% CI)=0.82 (0.71-0.95), P=0.01). The affected carriers of CT or TT also tended to have lower levels of serum AFP (P=0.01). This study demonstrated a role of rs11614913 in the etiology of HCC. Further research should focus on the clinical use of this miRNA SNP, so as to facilitate conquering HCC.

• Asian-Australasian Journal of Animal Sciences
• /
• v.29 no.11
• /
• pp.1555-1561
• /
• 2016

Shank skin color of Korean native chicken (KNC) shows large color variations. It varies from white, yellow, green, bluish or grey to black, whilst in the majority of European breeds the shanks are typically yellow-colored. Three shank skin color-related traits (i.e., lightness [$L^*$], redness [$a^*$], and yellowness [$b^*$]) were measured by a spectrophotometer in 585 progeny from 68 nuclear families in the KNC resource population. We performed genome scan linkage analysis to identify loci that affect quantitatively measured shank skin color traits in KNC. All these birds were genotyped with 167 DNA markers located throughout the 26 autosomes. The SOLAR program was used to conduct multipoint variance-component quantitative trait locus (QTL) analyses. We detected a major QTL that affects $b^*$ value (logarithm of odds [LOD] = 47.5, $p=1.60{\times}10^{-49}$) on GGA24 (GGA for Gallus gallus). At the same location, we also detected a QTL that influences $a^*$ value (LOD = 14.2, $p=6.14{\times}10^{-16}$). Additionally, beta-carotene dioxygenase 2 (BCDO2), the obvious positional candidate gene under the linkage peaks on GGA24, was investigated by the two association tests: i.e., measured genotype association (MGA) and quantitative transmission disequilibrium test (QTDT). Significant associations were detected between BCDO2 g.9367 A>C and $a^*$ ($P_{MGA}=1.69{\times}10^{-28}$; $P_{QTDT}=2.40{\times}10^{-25}$). The strongest associations were between BCDO2 g.9367 A>C and $b^*$ ($P_{MGA}=3.56{\times}10^{-66}$; $P_{QTDT}=1.68{\times}10^{-65}$). However, linkage analyses conditional on the single nucleotide polymorphism indicated that other functional variants should exist. Taken together, we demonstrate for the first time the linkage and association between the BCDO2 locus on GGA24 and quantitatively measured shank skin color traits in KNC.

• Asian-Australasian Journal of Animal Sciences
• /
• v.26 no.3
• /
• pp.323-333
• /
• 2013

This study investigated the geographic and pairwise distances of nine Chinese local Cashmere goat populations through the analysis of 20 microsatellite DNA markers. Fluorescence PCR was used to identify the markers, which were selected based on their significance as identified by the Food and Agriculture Organization of the United Nations (FAO) and the International Society for Animal Genetics (ISAG). In total, 206 alleles were detected; the average allele number was 10.30; the polymorphism information content of loci ranged from 0.5213 to 0.7582; the number of effective alleles ranged from 4.0484 to 4.6178; the observed heterozygosity was from 0.5023 to 0.5602 for the practical sample; the expected heterozygosity ranged from 0.5783 to 0.6464; and Allelic richness ranged from 4.7551 to 8.0693. These results indicated that Chinese Cashmere goat populations exhibited rich genetic diversity. Further, the Wright's F-statistics of subpopulation within total (FST) was 0.1184; the genetic differentiation coefficient (GST) was 0.0940; and the average gene flow (Nm) was 2.0415. All pairwise FST values among the populations were highly significant (p<0.01 or p<0.001), suggesting that the populations studied should all be considered to be separate breeds. Finally, the clustering analysis divided the Chinese Cashmere goat populations into at least four clusters, with the Hexi and Yashan goat populations alone in one cluster. These results have provided useful, practical, and important information for the future of Chinese Cashmere goat breeding.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.2093-2097
• /
• 2016

Background: HCV is a major global health problem. IL-27 is a member of the IL-6/IL-12 cytokine family with a broad range of anti-inflammatory properties. Recent studies highlighted the effect of a SNP in the IL-27 promoter region on modulating the progression of infectious diseases and individual responses to therapy. Aim of the work: The present study investigated the potential role of (-964 A/G) SNP in the promoter region of IL-27p28 gene (alleles rs153109) on the outcome of HCV infection among genotype 4a infected patients. Materials and Methods: HCV genotyping confirmed that all of the HCV-infected patients had genotype 4a infection. Genomic DNA was extracted from 111 patients with chronic HCV infection, 42 spontaneous resolvers (SR) and 16 healthy controls. IL- 27p28.rs153109 genotyping was assessed using PCR-RFLP then confirmed by DNA sequencing. Results: The frequency of IL-27-p28.rs153109AA, AG, and GG genotypes among chronically infected subjects were 74.8 %, 25.2%, and 0% while among the SR, they were 57.1%, 35.7%, and 7.14%, respectively. Our data show the unique presence of G/G genotype in the SR group (3 patients; 7.14%). Moreover, the "G" allele frequencies among chronic and resolved subjects were 12.6% and 25.0%, respectively (p=0.0136). Importantly, subjects with the GG genotype were more likely to clear their HCV infection than those with the AA genotype (p=0.0118). Conclusions: HCV genotype 4a subjects with the IL-27-p28.rs153109 A/G and G/G genotype were more likely to clear their HCV infection. Therefore, we propose IL- 27p28.rs153109SNPas a genetic biomarker for predicting HCV infection outcome.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.2
• /
• pp.1047-1055
• /
• 2014

Background: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. Methodology/Principal Findings: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-$196a2^*T$ variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. Conclusions: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

• Journal of Nutrition and Health
• /
• v.44 no.5
• /
• pp.366-377
• /
• 2011

Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA, plasma antioxidant vitamins, and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype, degree of DNA damage in lymphocytes, erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase (GSH-Px), and plasma concentrations of total radical-trapping antioxidant potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene, and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers, but the levels of plasma vitamin C, ${\beta}$-carotene, TRAP, erythrocyte catalase, and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1- or GSTT1-present genotype than those with the GSTM1-present or GSTT1- genotype. No difference in erythrocyte antioxidant enzyme activities, plasma TRAP, or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes, except ${\beta}$-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1- genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of ${\alpha}$-carotene, ${\beta}$-carotene, and cryptoxanthin. In conclusion, the GSTM1- and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently, the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1- or GSTT1-present genotypes might show significantly higher values than expected.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5145-5151
• /
• 2013

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.