• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2867-2871
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• 2012

Background: Multiple studies have reported associations between the PSCA rs2294008 C > T polymorphism and GC, but susceptibility has proven inconsistent. Therefore, we estimates the relationship between the rs2294008 C > T polymorphism and GC by meta-analysis. Methods: PubMed, Embase and Web of Science databases were searched and nine independent case-control studies were included in this meta-analysis. Crude ORs with 95% CIs were extracted according to the Mantal-Haenszel method and pooled to assess the strength of the association. Results: We observed that the PSCA rs2294008 C > T polymorphism was significantly correlated with GC risk when all studies were pooled into the meta-analysis. Further subgroup analysis showed the polymorphism to be linked with diffuse and noncardia GC in the allele contrast model, homozygote codominant model, dominant model, and recessive model. However, no connection was apparent for intestinal and cardia GC. In the stratified analysis by ethnicity, significant associations were observed in Asians for the recessive model. Interestingly, the relationship was particularly significant in the Chinese population. Conclusions: Our findings suggest that the PSCA rs2294008 C > T polymorphism is a risk factor for GC, especially in diffuse and noncardia GC and in Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3165-3172
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• 2012

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to 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. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10225-10229
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• 2015

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.387-393
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• 2016

Background: CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. Purpose: The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. Materials and Methods: Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BI-RADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. Results: No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p= 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p= 0.95; OR= 0.95; 95% CI= 0.51 - 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D'=1). Conclusions: Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1987-1992
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• 2015

The aim of this research was to investigate the possible association between gastric carcinoma (GC) and polymorphisms of the IL-$1{\beta}$ gene in the Kashmiri population using peripheral blood DNA from 150 gastric carcinoma cases and 250 population controls with detailed data for clinicopathological characteristics of the disease. Two SNPs in the IL-$1{\beta}$ gene were selected for this study. Expression of IL-$1{\beta}$ was studied in 50 gastric carcinoma cases using immunohistochemistry and RT-PCR and then correlated with genotype. The frequency of the IL-$1{\beta}$-511 C allele was significantly higher in the GC case group (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of 0.03. Multivariate regression analysis showed associations of gastric carcinoma with mutant form of IL-$1{\beta}$-511 TT (OR 0.309; P value <0.001) and the CC genotype of IL-$1{\beta}$-31 (OR 0.313; P value of 0.002). Haplotype analysis of IL-$1{\beta}$-31 and IL-$1{\beta}$-511 showed decreased association of IL-$1{\beta}$-31 T with IL-$1{\beta}$-511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of 50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade III and stage III+IV. After correlating the expression with polymorphism no association was found.

• Molecules and Cells
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• v.25 no.2
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• pp.265-271
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• 2008

Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation. Non-synonymous SNPs (nsSNPs) change an amino acid. Organic anion transporters (OATs) play an important role in eliminating or reabsorbing endogenous and exogenous organic anionic compounds. Among OATs, hOAT4 mediates high affinity transport of estrone sulfate and dehydroepiandrosterone sulfate. The rapid bone loss that occurs in post-menopausal women is mainly due to a net decrease of estrogen. In the present study we searched for SNPs within the exon regions of hOAT4 in Korean women osteoporosis patients. Fifty healthy subjects and 50 subjects with osteoporosis were screened for genetic polymorphism in the coding region of SLC22A11 (hOAT4) using GC-clamp PCR and denaturing gradient gel electrophoresis (DGGE). We found three SNPs in the hOAT4 gene. Two were in the osteoporosis group (C483A and G832A) and one in the normal group (C847T). One of the SNPs, G832A, is an nsSNP that changes the $278^{th}$ amino acid from glutamic acid to lysine (E278K). Uptake of [$3^H$] estrone sulfate by oocytes injected with the hOAT4 E278K mutant was reduced compared with wild-type hOAT4. Km values for wild type and E278K were $0.7{\mu}M$ and $1.2{\mu}M$, and Vmax values were 1.8 and 0.47 pmol/oocyte/h, respectively. The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis.

• Korean Journal of Veterinary Research
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• v.40 no.4
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• pp.683-689
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• 2000

The present study was carried out to investigate the blood markers of Thoroughbred horses (TB) The blood red cell types and blood protein types (biochemical polymorphisms) were tested from 1,125 Thoroughbred horses by serological and electrophoretic procedures, and their phenotypes, gene frequencies, heterozygosity, polymorphic information content values and exclusion probability were estimated. The blood group and biochemical polymorphism phenotypes observed with high frequency were Aaf(91.7%), Ca(94.7%), K-(94.5%), Ua(75.9%), P-(50.6%), Qabc(82.6%), ALB-BB(67.7%), GC-FF(92.7%), AIB-KK(99.6%), ES-II(77.9%), TF-DF1(23.6%), PI-LL(23.2%), HB-B2B2(73.6%), PGD-FS(45.4%) and genotypes Dcgm/dk(16.9%), Dbcm/cgm(13.6%), Dbcm/dk(11.9%), Dcegmn/cegmn(10.0%), Dcgm/cgm(8.7%) in TB. Alleles observed with high frequency were Aaf(0.796), Ca(0.769), Ddk(0.266), Dcgm(0.261), Dbcm(0.211), K-(0.972), P-(0.710), Qabc(0.565), Q-(0.368), Ua(0.509), $HB^{B2}$(0.858), $PGD^F$(0.634), $ALB^B$(0.825), $GC^F$(0.927), $AIB^K$(0.998), $ES^I$(0.881), $TF^{F1}$(0.346), $TF^D$(0.319), $TF^{F2}$(0.184), $PI^L$(0.479), $PI^N$(0.214), $PI^U$(0.116) in TB. The heterozygosity, polymorphic information content (PIC) and exclusion probability (PE) were calculated. The mean heterozygosity and PIC value were 0.3899 and 0.3375, respectively. The highest heterozygosity and PIC were estimated 0.7834 and 0.7492 in blood group D locus, respectively. The cumulated PE obtained by blood groups and biochemical polymorphisms was 0.9813.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2951-2957
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• 2014

Background: Gastric carcinogenesis is a complicated process that involves environmental and genetic factors like interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changed levels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A and gastric cancer (GC) risk in Sichuan of Southwestern China. Materials and Methods: We surveyed the research subjects using a self-designed questionnaire with questions on demographic factors and putative risk factors. Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>A genotypes using MALDI-TOF MS. Results: Our study recruited 308 pairs of GC patients and controls, including 224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients in the case group. The case and control groups had an average age of $57.7{\pm}10.6$ ($mean{\pm}SD$) and $57.6{\pm}11.1$ years. GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01) and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>A were not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjusted OR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites only found that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjusted OR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking (adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardia GC. Conclusions: Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overall GC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to the evidence body for risk of SNPs associated with the development of gastric cancer in this region.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7467-7472
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• 2013

Background: Polymorphisms of genes encoding cytokines could be potential biomarkers to predict risk of gastric cancer (GC). Here, we investigated the association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter region and GC risk. Methods: In this case-control study of 215 GC cases and 518 non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Individuals with the TC or CC genotype were associated with a significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049) compared with TT wild-type carriers. Ther C allele was also associated with significantly decreased risk of GC (OR=0.715, 95%CI: 0.536-0.954, P=0.023) compared with the T allele. In the stratification analysis, TC or CC genotypes were associated with significantly decreased GC risk in subgroups of males, people older than 60, and H. pylori-positive cases. However, no significant interaction was observed for TC or CC genotypes with H. pylori infection. On stratification with the Lauren classification, TC or CC genotypes were associated with significantly decreased risk of diffuse-type GC (OR=0.497, 95%CI: 0.266-0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori-positive cases. Conclusions: The IL-6 -6331 (T/C, rs10499563) polymorphism is associated with genetic susceptibility of GC and may have the potential to predict GC risk.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.11
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• pp.1545-1550
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• 2015

c-MYC (v-myelocytomatosis viral oncogene homologue) is a transcription factor that plays important role in many biological process including cell growth and differentiation, such as myogenesis and adipogenesis. In this study, we aimed to detect MYC gene polymorphisms, their genotype frequencies and to determine associations between these polymorphisms and meat quality traits in Berkshire pigs. We identified a single nucleotide polymorphism (SNP) in intron 2 of MYC gene by Sanger sequencing, i.e., g.3350G>C (rs321898326), that is only found in Berkshire pigs, but not in other breeds including Duroc, Landrace, and Yorkshire pigs that were used in this study. Genotypes of total 378 Berkshire pigs (138 sows and 240 boars) were determined using Hha I restriction enzyme digestion after polymerase chain reaction. Observed allele frequencies of GG, GC, and CC genotypes were 0.399, 0.508, and 0.093 respectively. Statistical analysis indicated that the g.3350G>C polymorphism was significantly associated with $pH_{45min}$ and cooking loss (p<0.05), suggesting that g.3350G>C SNP can be used for pre-selection of $pH_{45min}$ and cooking loss traits in Berkshire pigs.