Association between Epstein-Barr Virus Gene Polymorphism and Breast Cancer Risk among Egyptian Females.

BACKGROUND: Epstein-Barr virus (EBV) has been implicated in the development of breast cancer (BC) since 1995. It is classified into A/B genotypes, C/D subtypes, and F/f variants according to variations in its genome. AIM: To determine the distribution difference of EBV types between BC patients and healthy controls in Egypt and to detect the association between different EBV types and BC characteristics. METHODS: Three hundred and sixty-two participants (142 BC patients and 220 controls) were enrolled in this study. All participants were screened for EBV infection by determination of viral-capsid-IgG antibodies in their sera. EBNA-1 gene was detected by PCR in tumor biopsies of seropositive patients and in peripheral blood mononuclear cells of controls. A/B genotyping of EBV was performed by nested-PCR targeting the EBNA-2 gene. C/D subtypes and F/f variants were identified by Restriction fragment length polymorphism at BamHI-I W1/I1 and BamHI-F regions of EBV genome, respectively. RESULTS: Among 362 participants, 300(82.9%) were EBV-seropositive, including 120/142(84.5%) of the BC patients and 180/220(81.8 %) of the controls. EBNA-1 gene was positive in 54(45%) of seropositive BC patients and in 38(21.1%) of seropositive controls. There was a significant association of EBNA-1 gene with breast cancer (OR=3.05, 95%CI=1.84-5.07). Moreover, EBNA-1 gene positivity was significantly associated with the more aggressive tumors. Genotype-A and prototype-F were predominant among patients (90.4%, 100%, respectively) as well as among controls (91.7%, 100%, respectively) with no statistical significant association with BC risk.  However, subtype-D was significantly more frequent in patients (95.6%) than in controls (64.7%) and was significantly associated with a higher BC risk as compared to subtype-C (OR=11.7, 95%CI=2.4-57.08). Subtype-D was significantly associated with higher grades tumors (100% among grade III),  with progesteron receptor-negative tumors and with HER2-positive tumors (100% for each). The combined genotypes that significantly associated with BC risk were ADF (OR=4.9) and BDF (OR=5.5). CONCLUSIONS: Subtype-D of EBV could be the only EBV type implicated in BC development among Egyptian females and associated more with poor prognosis.

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

INTRODUCTION: Leptin is a hormone secreted from adipocytes that regulates metabolism and energy homeostasis through the leptin receptor (LEPR). The aim of this study was to investigate the association of leptin receptor gene Q223R gene polymorphism, and plasma leptin level among obese breast cancer females. MATERIALS AND METHODS: The study enrolled 160 breast cancer patients and 160 healthy control females. LEPR Q223R polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum leptin was determined using enzyme-linked immunosorbent assay human leptin kit.  Immunohistochemical tests from paraffin blocks were carried out for estrogen and progesterone staging using the precise antibodies. RESULTS: An association was found between LEPR gene Q223R gene polymorphism among obese breast cancer females. Statistical difference was found between GG (60.6%) Arg/Arg genotype (OR=2.986; 95%CI=1.540 to 5.789; p= 0.001) compared to AA (33.1%) Gln/Gln genotype. GG Q223R LEPR polymorphism showed statistically significant difference among obese breast cancer patients (BMI more than 25) compared to control (P < 0.0001). GG genotype of Q223R LEPR polymorphism showed statistically significant increased leptin level (p-value =0.0001) among obese patients (mean± SD; 23.39±4.32) compared to control (17.83±5.67). CONCLUSIONS: Q223R LEPR polymorphism GG genotype was associated with increased leptin profile among obese breast cancer females.

PCR-RFLP Based genetic diversity of Plasmodium vivax genotypes in district Mardan, Pakistan / Diversidade genética baseada em PCR RFLP de genótipos de Plasmodium vivax no distrito de Mardan, Paquistão

Plasmodium vivax is the most common human malaria parasite in Asian countries including Pakistan. Present study was designed to explore the genetic diversity of plasmodium vivax genotypes based on Pvmsp-3α and Pvmsp-3βgenes using allelic specific nested PCR and RFLP assays markers from field isolates in district Mardan, Pakistan. Blood samples of 200 P. vivax malarial patients were collected after taking their written informed consent. Genetic diversity in nested PCR products was determined by Restriction Fragment Length Polymorphism (RFLP) utilizing Alu1 and PstI restriction enzymes for alpha and beta gene products digestion, respectively. For analysis the genetic diversity of the sub allelic variants of Pvmsp3α and Pvmsp3β genes, Chi-Square test was performed by utilizing Minitab programming software 18. The P value 0.05 was considered as statistically significant. For Pvmsp 3α genes after gel electrophoresis of digested products, four distinct genotypes were obtained from total of 50 samples; type A: 35 (70%) (1.5-2.0 kb), 12 of type B (24%) (1.5-1.7 kb), 2 of type C (4%) (0.5-1.5) and one for type D (2%) (0.5-0.65 kb) which could be characterized into 9 allelic pattern (A1-A4, B1-B3, C1, D), in which A3 remained the most predominant. For Pvmsp-3βgenes, three distinct genotypes were obtained from 50 samples; 40(80%) of type A (1.5-2.5 kb), 9 (18%) of type B (1.0-1.5kb) and 1(2%) of type C (0.65 kb) which could be characterized into 6 allelic patterns (A1-A3, B1-B2, and C1). Most dominant one in Type A was A1 alleles which were noted (46%), while in Type B, the most dominant were B1 (10%).This study is the first ever report of molecular epidemiology and genetic variation in Pvmsp-3α and Pvmsp-3β genes of P. vivax isolates by using PCR/RFLP from District Mardan and [...].

O Plasmodium vivax é o parasita da malária humana mais comum nos países asiáticos, incluindo o Paquistão. O presente estudo foi desenhado para explorar a diversidade genética de genótipos de Plasmodium vivax baseados nos genes Pvmsp-3α e Pvmsp-3β, usando marcadores de ensaios alélicos nested PCR e RFLP de isolados de campo no distrito de Mardan, Paquistão. Amostras de sangue de 200 pacientes com malária por P. vivax foram coletadas após assinatura do termo de consentimento livre e esclarecido. A diversidade genética em produtos de PCR nested foi determinada por polimorfismo de fragmento de restrição (RFLP) utilizando as enzimas de restrição Alu1 e PstI para a digestão dos produtos dos genes alfa e beta, respectivamente. Para análise da diversidade genética das variantes subalélicas dos genes Pvmsp3α e Pvmsp3β, o teste Qui-quadrado foi realizado utilizando o software de programação Minitab 18. O valor P = 0,05 foi considerado estatisticamente significativo. Para os genes Pvmsp 3α, após eletroforese em gel de produtos digeridos, quatro genótipos distintos foram obtidos de um total de 50 amostras; tipo A: 35 (70%) (1,5-2,0 kb), 12 do tipo B (24%) (1,5-1,7 kb), 2 do tipo C (4%) (0,5-1,5) e um para o tipo D (2%) (0,5-0,65 kb), que podem ser caracterizados em nove padrões alélicos (A1-A4, B1-B3, C1, D), em que A3 permaneceu como o mais predominante. Para Pvmsp-3βgenes, três genótipos distintos foram obtidos a partir de 50 amostras; 40 (80%) do tipo A (1,5-2,5 kb), 9 (18%) do tipo B (1,0-1,5 kb) e 1 (2%) do tipo C (0,65 kb), que podem ser caracterizados em seis padrões alélicos (A1-A3, B1-B2 e C1). Os mais dominantes no tipo A foram o alelo A1, observados em 46%, enquanto, no tipo B, os mais dominantes foram B1 (10%). Este estudo é o primeiro relato de epidemiologia molecular e variação genética em Pvmsp-3α. Os genes Pvmsp-3β de isolados de P. vivax utilizando PCR/RFLP do Distrito Mardan mostraram um nível notável de diversidade genética nos genes estudados [...].

Presence of atypical genotypes of Toxoplasma gondii isolated from cats in the state of Bahia, Northeast of Brazil.

In this study, 20 blood, heart, and brain samples were collected from euthanized cats at the Zoonosis Control Centers and Veterinary Clinics in the state of Bahia, Brazil. The sera were examined for anti-T. gondii antibodies using the indirect hemagglutination test. The brains and hearts of seven seropositive cats were ground, and peptide digestion was performed for bioassay in mice. Toxoplasma gondii was isolated in 5/7 (71.42%) of seropositive cats. In these isolates, the parasite was genotyped using the Polymerase chain reaction, associated with the DNA fragment polymorphism obtained by restriction enzyme PCR-RFLP technique with 11 markers (SAG1, 5'-SAG2, 3'-SAG2, alt. SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico, and CS3) and 15 microsatellite markers (TUB-2, W35, TgM-A, B18, B17, M33, IV.1, XI.1, M48, M102, N60, N82, AA, N61, N83). The analysis of the isolates by PCR-RFLP revealed five distinct genotypes. Three of these genotypes have never been reported before; one corresponded to the TgDgCo13 genotype, and one incomplete genotype. In genotyping analysis using microsatellite markers, it was observed that the isolates showed atypical alleles in the typing and fingerprint markers. This revealed five atypical genotypes. The typing marker B17 showed the highest degree of atypia. This study is the first to report the genotyping of T. gondii obtained from naturally infected cats in Bahia, Northeast Brazil. The genotypes found in this study were different from those found in other studies conducted in Bahia, which included different species of animals. None of the clonal lineages I, II, or III were found. This study demonstrates the diversity of T. gondii in the study region, with the presence of unusual genotypes, reaffirming the genetic variability of the parasite in Brazil.

Investigation of the relationship between MMP-1 (- 1607 1G/2G), MMP-3 (- 1171 5A/6A) gene variations and development of bladder cancer.

BACKGROUND: Chronic inflammation is an important risk factor in the development of bladder cancer. It may stimulate growth and metastasis of cancer cells. The inflammatory process includes MMP activities and expression. MMP activation can be stimulated by various inflammatory cells. Pathological processes such as bladder cancer may occur due to imbalance in MMP activities. In our study, we aimed to determine the relationship between MMP-1, MMP-3 gene variations associated with chronic inflammation and the bladder cancer development. METHODS: Our study was carried out with 89 bladder cancer patients and 78 healthy controls. PCR-RFLP methods were applied to determine MMP-1 and MMP-3 gene variations genotype distributions. RESULTS: 1G/1G homozygous and 1G/2G heterozygous genotypes of MMP-1 gene variation were determined more in patients than controls. The 5A/5A homozygous and 5A/6A heterozygous genotypes of the MMP-3 gene variation were detected more in patients than controls. The significant difference was detected in terms of genotype distributions of MMP-1 and MMP-3 gene variations between these groups (p < 0.05). In addition to, the most common haplotype in the patient group were detected as 1G/2G-5A/6A (20.22%). CONCLUSION: In this study, MMP-1 and MMP-3 gene variations were determined as possible genetic risk factors for bladder cancer development in the Thrace population.

The Association of MMP9 Promoter Rs3918242 Genotype With Gastric Cancer.

BACKGROUND/AIM: Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk. MATERIALS AND METHODS: MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples. RESULTS: MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index. CONCLUSION: Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

Molecular epidemiology of Mycobacterium tuberculosis in Brazil before the whole genome sequencing era: a literature review

Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.

Association of Caspase-8 Genotypes With the Risk for Nasopharyngeal Carcinoma in Taiwan.

BACKGROUND/AIM: Accumulating evidence shows that caspase-8 (Cas-8) rs3834129 genotypes determine susceptibility to various cancers, but their association with nasopharyngeal carcinoma (NPC) has not been examined. We aimed at investigating the association of Cas-8 rs3834129 with NPC risk. MATERIALS AND METHODS: Cas-8 rs3834129 genotypes and their associations with NPC risk were investigated among 176 NPC patients and 352 non-cancer subjects by the PCR-RFLP method. Additionally, the interaction of Cas-8 rs3834129 genotypes with smoking was examined. RESULTS: The II, ID and DD frequencies were 56.8, 36.9 and 6.3% among NPC patients and 54.8, 38.1 and 7.1% among control subjects (ptrend=0.8830). Allelic frequency distribution analysis also indicated that the D allele is not a risk factor for NPC (p=0.6183). There was no interaction between Cas-8 rs3834129 and smoking and NPC risk (p=0.8305). CONCLUSION: Cas-8 rs3834129 genotypes play a minor role in the risk for NPC.

The Contribution of Interleukin-12A Genotypes to Oral Cancer Risk in Taiwanese.

BACKGROUND/AIM: Oral cancer incidence is highest worldwide in Taiwan, and practical markers for personalized therapeutic strategies such as immunotherapies, is lacking. Interleukin-12 (IL12) is a cytokine that is reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. We aimed to examine whether IL12A rs568408 and rs2243115 genotypes are associated with oral cancer risk in Taiwan. MATERIALS AND METHODS: Genotypic characteristics of IL12A were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The variant genotypes of IL12A rs568408 and rs2243115 were not found to be significantly associated with elevated oral cancer risk (all p>0.05). Moreover, there was no interaction between IL12A genotypes and personal smoking, alcohol drinking and betel quid chewing behaviors (all p>0.05). CONCLUSION: IL12A rs568408 and rs2243115 genotypes may not serve as good predictors for oral cancer risk.

RUNX3 Polymorphisms Affect the Risk of Ankylosing Spondylitis.

BACKGROUND We aimed to assess the potential association of runt-related transcription factor 3 (RUNX3) gene variants with ankylosing spondylitis (AS) susceptibility among Chinese Han people. MATERIAL AND METHODS Genotyping for RUNX3 variants was accomplished through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 115 AS patients and 102 healthy controls. Genotypes distributions of the polymorphisms in controls was assessed for their deviation from Hardy-Weinberg equilibrium (HWE). Moreover, odds ratio (OR) with 95% confidence interval (95%CI) was achieved using chi-square analysis to evaluate AS risk related to RUNX3 polymorphisms. Additionally, logistic regression analysis produced adjusted OR values. RESULTS Genotypes distribution of rs760805 and rs11249206 polymorphisms conformed to HWE in the control group (P>0.05). TT genotype of rs760805 appeared more frequently among AS cases than in controls (P=0.033), indicating its significant association with increased risk of AS onset (OR=2.309, 95%CI=1.069-4.892). The carriage of T allele in rs760805 also heightened AS incidence, in comparison to A allele (OR=1.578, 95%CI=1.075-2.316, P=0.020). Moreover, the carriage of AT+TT genotype in rs760805 and TT genotype in rs11249206 obviously increased risk of AS onset (OR=2.585, 95%CI=1.062-6.288). CONCLUSIONS RUNX3 rs760805 polymorphism can contribute to AS incidence in Chinese Han people. The interaction of the 2 polymorphisms may be a risk factor for AS.

Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges.

Background: High heterogeneity levels of cystic fibrosis transmembrane regulator (CFTR) are manifested in different populations. The aim of this study was to analyze comprehensively all mutations in the CFTR gene in Serbian patients with cystic fibrosis (CF) and to use the findings to propose a testing algorithm for the Serbian population. Materials and Methods: Cascade screening was employed to detect mutations in the CFTR gene of 90 patients suspected of having CF, using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism or PCR-mediated site directed mutagenesis, Sanger sequencing, and/or next-generation sequencing. Results: This is the first report for the Serbian CF population where single nucleotide polymorphisms, small insertions and deletions, large genome rearrangements, and copy number variants were analyzed in detail. A high degree of heterogeneity within the CFTR was documented among our cohort of 90 patients. We identified 19 CF-causing mutations and 3 with varying consequences, including a previously unreported deletion of the entire exon 11. Conclusion: Considering the spectrum and frequency of mutations found, we recommend a multistep sequencing algorithm in combination with evaluation of large rearrangements for future analyses of the CFTR gene in the Serbian population.

Association of estrogen receptor gene variants (ESR1 and ESR2) with polycystic ovary syndrome in Tunisia.

SNV (single nucleotide variation) in estrogen receptor (ESR1 and ESR2) genes are susceptibility markers for complex diseases, such as cancer, metabolic disorders and women infertility. We explored six widely used SNVs in ESR1 (rs2234693, rs9340799, rs3798577, rs3020314) and ESR2 (rs1256049, rs4986938) in polycystic ovary syndrome (PCOS) in women from Tunisia (n = 254) compared to controls (n = 170). Genotyping was performed by RFLP-PCR or real-time PCR and analyzed in GoldenHelix statistical package. Logistic regression revealed association of rs2234693, rs3798577 and rs3020314 (ESR1) and rs1256049 (ESR2), the association of rs2234693 (C/T) being the strongest with P < 4.81 × 10-6, 2.88 × 10-5 after Bonferroni correction, OR 0.31, 95%CI (0.18-0.53)). Correlations were found with LH, LH/FSH or hyperandrogenism and even more significant with metabolic syndrome (rs9340799) and hyperglycemia (rs3798577). Among 14 haplotypes reconstructed in ESR1gene, four haplotypes (H1 to H4) were associated with PCOS the strongest being that of H1 (P < 0.002) supported by Bonferroni (P < 0.033) and permutation tests (P < 4 x10-4). In haplotype trend regression, concordant correlations were found with insulin resistance (P < 0.033) for H2 and with high blood pressure for H3 (P < 0.048). While these data revealed influential role on metabolic rather and hormonal features of PCOS, the association of rs2234693 was the strongest among all ethnic populations studied thus far giving a new insight on estrogen receptor gene variation in distant North African populations and their role in metabolic alteration of PCOS.

Mutational Variation Analysis of oprD Porin Gene in Multidrug-Resistant Clinical Isolates of Pseudomonas aeruginosa.

The present study deals with the outer membrane OprD porin protein in 29 clinical bacterial isolates of multidrug-resistant Pseudomonas aeruginosa. oprD porin gene expression was investigated using real-time reverse transcription-PCR. Amplicons from oprD and its transcriptional regulator mexT gene were sequenced and analyzed for mutations. Hypothetical models of selected mutant OprD-porin proteins were predicted and refined by homology modeling approach. oprD ampliconic sequences were also screened for restriction fragment length polymorphism (RFLP). The oprD gene was found to be downregulated in 89.7% (n = 26) of the isolates in comparison to the transcript levels in the reference strain P. aeruginosa-PAO (MTCC-3541). Interestingly, all these isolates displayed the presence of a conspicuous 8-bp deletion (GGCCAGCC) at nucleotide position 235 of mexT regulatory gene. Based on the mutational patterns observed in oprD gene, the isolates were classified into categories designated as A, B1-2, C1-4, D1-6, E1-2, and F. Our hypothetical models revealed that mutations were predominantly confined to the extracellular loops emanating from the ß-barrel porin protein. These protein models also enabled clear visualization of loss of substantial portions of the truncated polypeptide. Incidentally, since most of the oprD amplicons of the clinical isolates were found to display distinct RFLP banding patterns, our results also provide a useful diagnostic tool for detection of P. aeruginosa porin mutants.

Promoter polymorphisms in IL-6 gene influence pro-inflammatory cytokines for the risk of osteoarthritis.

BACKGROUND: Interleukin-6 (IL-6) gene regulates IL-6 levels, interplay of which has been found to influence pathophysiology of osteoarthritis (OA). Polymorphism within promoter region of IL-6 gene and its association with plasma levels of pro-inflammatory cytokines; IL-6, interleukin 1-beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) remained to be investigated in Punjab region of India, where OA is highly prevalent. METHODS: Six single nucleotide polymorphisms (SNPs) in the promoter region of IL-6 gene; rs1800795 (-174G/C), rs1800796 (-572G/C), rs1800797 (-597G/A), rs2069827 (-1363G/T), rs12700386 (-2954G/C) and rs10499563 (-6331G/T) were investigated by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 279 confirmed osteoarthritis patients and 287 controls. Plasma levels of pro-inflammatory cytokines; IL-6, IL-1ß and TNF-α were measured by sandwich Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: Allele frequency spectrum after adjusting the effect of systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein (LDL), triglycerides (TG) and body mass index (BMI) revealed that major allele G of rs1800795 and T of rs10499563 were significantly associated with increased risk of OA (P < 0.01) in all the three genetic models; co-dominant (OR 4.08 & 4.12, P < 0.001), recessive (OR 3.00 & 2.51, P < 0.001) and dominant (OR 2.56 & 3.09, P < 0.05). Major allele G of rs1800796 and rs1800797 was observed to enhance OA risk in recessive mode (OR 1.75, P < 0.001 & 1.62, P = 0.01 respectively). Disease risk analysis after adjusting the effect of confounders exposed a susceptibility haplotype GGGGCT, which increased the OA risk by 2.27 times (OR 2.27, 95%CI: 1.26-4.10, P = 0.009) and a protective haplotype CGAGGC which significantly reduced the OA risk (OR 0.47, 95%CI 0.27-0.92, P = 0.031). Both of these haplotypes manifested in the recessive mode of inheritance. Subjects who had one copy of the susceptibility haplotype had lower values of IL-6 (3.6 pg/ml) and IL-1ß levels (3.2 pg/ml) than those who had 2 copies of it (4.4 pg/ml & 4.2 pg/ml respectively). IL-6 and IL-1ß levels were observed to be negatively associated with protective haplotype CGAGGC (P < 0.05). Carriers of 1 copy of this haplotype showed decreased IL-1ß levels than those who had none (1.00 pg/ml vs. 1.3 pg/ml respectively) which further decreased to 0.9 pg/ml in those subjects who carried two copies of protective haplotype. CONCLUSION: The present study discovered susceptibility (GGGGCT) and protective (CGAGGC) haplotypes within promoter region of IL-6 gene which influenced the plasma levels of IL-6 and IL-1ß for the risk of osteoarthritis in the population of Punjab, India.

The Influence of Family History on Stage and Survival of Gastric Cancer According to the TGFB1 C-509T Polymorphism in Korea.

Background/Aims: The survival rate of gastric cancer (GC) is known to be higher in patients with a family history (FH) of GC. There is an association between a polymorphism in the transforming growth factor-ß1 (TGFB1) gene and the risk of GC in patients with first-degree relatives with GC. This study was performed to investigate whether a FH affects GC outcomes according to the TGFB1 C-509T polymorphism. Methods: TGFB1 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 1,143 GC patients, including 216 patients (18.9%) with first-degree relatives with GC. Results: The proportion of stage I-II GCs was significantly higher in patients with a FH than in those without a FH of GC (83.8 vs 74.9%, p=0.005). The association between a FH of GC and stage I-II GC was not significant in subgroups divided based on the TGFB1 C-509T polymorphism and sex. A FH did not affect the overall survival rate of GC in patient with all stages and each stage. The overall survival rates were not significantly different between patients with the CC and CT/TT genotypes of the TGFB1-509 polymorphism. Conclusions: Patient with a FH of GC had lower cancer stage (I-II) at diagnosis than those without a FH of GC, but there was no significant difference in overall survival between the patients with and without a FH of GC. A FH did not influence the tumor stage or overall survival in patients stratified by the presence of the TGFB1 C-509T polymorphism.

Significant Association of miR-605 rs2043556 with Susceptibility to Breast Cancer.

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNA molecules, which directly regulate gene expression. It has been documented that single nucleotide polymorphisms in miRNA genes could alter the regulation of miRNA expression and function. OBJECTIVE: In this study, the allele and genotype frequency of miR-605 rs2043556 and its association with breast cancer were investigated in the Iranian population. METHODS: Genotyping was performed in 162 females affected with breast cancer and 180 healthy individuals. Genotyping was performed using Restriction Fragment Length Polymorphism (RFLP) followed by Sanger sequencing. RESULTS: The data showed the presence of Hardy Weinberg equilibrium (HWE) for this marker in the Iranian population. Allelic frequency for A and G allele was 0.75 and 0.25, respectively. Odd ratios for the association between miR-605 rs2043556 AG/GG genotypes was 3.86 with p-value= 0. CONCLUSION: The results indicated an increased risk for breast cancer susceptibility for miR-605 rs2043556 in the Iranian population.

Nuclear factor-κB1 and MicroRNA-146a polymorphisms and risk of acute graft versus host disease post allogeneic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) is a severe inflammatory complication of haematopoeitic stem cell transplantation. The nuclear factor- Kappa Beta (NF-κB) signaling pathway regulates T cell activation. The NF-κB controls the expression of microRNA-146a (miR-146a) that in turn regulates NF-κB activation through a negative feedback loop. We aim to analyze the association between NF-κB1 encoding p50 (rs28362491, -94 in.ertion/deletion ATTG) and miR-146a (rs2910164, G > C) polymorphisms and risk of aGVHD. Genotyping was performed for 135 HLA-matched donors using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).The incidence of aGVHD grades II-IV was 24/135 (17.8 %). NF-κB1 genotype and cytomegalovirus infection were significantly associated with risk of aGVHD II-IV (p = 0.022, HR = 3.17, 95 % CI:1.18-8.51 and p = 0.048, HR = 2.56, 95 % CI:1.01-6.52, respectively). In multivariate analysis, NF-κB1homozygous deletion/deletion genotype was the only independent risk factor associated with aGVHD II-IV (p = 0.013, HR = 3.50, 95 % CI:1.30-9.44). No significant association could be observed between miR-146a polymorphism and aGVHD. Combined NF-κB1 and miR146a genotype analysis warrants investigation in a larger cohort. Our preliminary data do not support the association between miR146a and aGVHD, but suggest an association between NF-κB1 and risk of aGVHD that may pave the way for the development of a novel targeted therapy if proved in a larger cohort.

Association study between CYP24A1 gene polymorphisms and cancer risk.

CYP24A1, an essential gene in regulation of vitamin D, has been reported to play an important role in enhancing immune activity and inhibiting tumorigenesis. Previous studies proposed that rs2585428, rs4809960, rs6022999 and rs6068816 in CYP24A1 gene might be greatly associated with cancer risk. To validate the findings, we here investigated the associations of these four polymorphisms and colorectal cancer (CRC) risk in a central Chinese population (426 colon cancer patients, 361 rectal cancer patients and 800 healthy controls). The genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results revealed that the rs4809960 and rs6022999 were strongly associated with the CRC risk, especially with the colon cancer risk. Moreover, the analysis of haplotypes consisting of rs2585428(G > A), rs4809960(T > C), rs6022999(A > G) and rs6068816(C > T) indicated that haplotype ATGC significantly decreased the CRC risk, especially the colon cancer risk. Haplotype GCAT significantly increased the CRC risk, especially the rectal cancer risk. However, haplotype ACAC was only found to be associated with increased risk of CRC. To improve the statistical strength, an updated meta-analysis was further performed. The results showed that rs2585428 was associated with cancer risk in Caucasian population, rs4809960 was associated with breast cancer risk in Caucasian population, and rs6022999 was associated with cancer risk in Asian population. Collectively, the rs4809960 and rs6022999 may be the genetic biomarkers for prediction of colon cancer risk in Chinese population, the rs2585428 and rs6022999 may link to cancer susceptibility in Caucasian population and in Asian population respectly.

Investigation of JAM-A (rs790056) and LFA-1 (rs8058823) gene variants in Turkish colorectal cancer patients.

BACKGROUND/AIMS: Lymphocyte function-associated antigen 1 (LFA-1) is a transmembrane glycoprotein expressed on the surface of leukocytes and containing the binding domain for junctional adhesion molecule-A (JAM-A). The aim of the present study was to evaluate the effects of JAM-A and LFA-1 variants on the formation of colorectal cancer and metastasis. MATERIALS AND METHODS: A total of 82 subjects with colorectal cancer and 67 healthy subjects were studied. DNA was isolated from blood samples, and variations were determined using the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: JAM-A rs790056 CC genotype and C allele were found to be higher in the colorectal cancer group (p<0.05), and approximately 3-fold increased colorectal cancer risk with CC genotype was determined (p=0.029). Haplotype analysis showed that GC haplotype (LFA-1 rs8058823G and JAM-A rs790056C) frequency was significantly higher in the patient group (p=0.041) than in controls. CONCLUSION: JAM-A rs790056 variation may be effective in the development of colorectal cancer.

The EGFR rs2233947 polymorphism is associated with lung cancer risk: a study from Jordan.

The epidermal growth factor receptor (EGFR) is a tyrosine kinase cell surface protein that plays a role in the process of carcinogenesis. In this study, we investigated the association between EGFR rs2233947 and rs884225 SNPs and the risk of lung cancer. A total of 258 participants (129 lung cancer patients and 129 healthy controls) took part in the study. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used to genotype EGFR SNPs. A strong association was detected between rs2233947 and lung cancer (P<0.01). Compared with the rs2293347 GG genotype, the AA/AG genotypes were associated with a significantly decreased risk of lung cancer (adjusted OR = 0.28, 95% confidence interval [CI]=0.13-0.61, P<0.01). EGFR rs2233947 correlated with lung cancer in males, smokers, and in the squamous cell carcinoma lung cancer subtype (P<0.01). Haplotype analysis of rs2233947 and rs884225 showed that the AA haplotype was associated with a significantly decreased risk of lung cancer (P<0.01). The data presented in the current study support a protective role for the rs2233947 A allele against the development of lung cancer. This result, however, requires further validation in a larger population.