Association between Vitamin D Receptor Polymorphism and Susceptibility to Oral Lichen Planus and Oral Squamous Cell Carcinoma.

Introduction: Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80-90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. Materials and Methods: In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. Results: A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. Conclusion: There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

Attitudes and Beliefs Towards Transgender Individuals Among Residents of Mashhad, Iran in 2020.

A growing number of studies show that transgender people are at higher risk for psychiatric morbidities. This increased vulnerability can result from the discrimination, violence, and other forms of stigma transgender people experience. Several studies have assessed the stigma by studying the public attitudes and beliefs towards transgender people. Using the Genderism and Transphobia Scale, we evaluated how citizens of a metropolitan city in Iran think and feel about transgender people. A total number of 1202 participants, with a mean age of 41.57 years ± 13.41 (27.4% cisgender men and 72.6% cisgender women), were recruited via a random cluster sampling. Demographic data and socioeconomic status were collected for all the participants. The findings showed a notable level of transphobia. Participants identifying as men, being single, personally acquainted with a transgender individual, possessing a higher education, and having a higher socioeconomic standing displayed significantly more positive views towards transgender people. Iranian transgender people, living under a theocratic state, experience more challenges compared to those live in Western countries. Our findings demonstrate that educational level accounted for much of the variance in transgender attitudes. Therefore, representing transgender issues in social media can educate the general population and positively change attitudes and behaviors.

Potential Role of Zinc Finger 365 rs10822013 and rs10995190 in Mammographic Density, Sporadic Breast Cancer Risk, and Prognosis.

Background: Despite suggesting many genetic risk markers as the outcome of Genome-wide association studies (GWAS) for breast cancer, replicating the results in different populations has remained the main issue. In this regard, this study assessed the association of two variations in Zinc Finger 365 (ZNF365) in an Iranian population. Methods: In a case-control study conducted at Mashhad University of Medical Sciences, Mashhad, Iran, between 2017 and 2020, ZNF365-rs10822013 and rs10995190 were genotyped using Allele-Specific PCR (AS-PCR). Breast density was assessed using mammography images. PHASE software module version 2 and SPSS version 16.0 were used for haplotype and statistical analyses. Quantitative and qualitative variables were compared between groups using independent t tests and Chi square tests, respectively. Binary logistic regression analysis was performed to calculate odds ratios. Multivariate analysis was then undertaken for the baseline variables, with a P<0.05 in the univariate analysis. The survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: In this survey, 732 females, including 342 breast cancer patients and 390 healthy subjects, were enrolled. rs10822013-T allele (P=0.014), rs10995190-G allele (P=0.003), and TG haplotype (P=0.002) were significantly associated with the increased risk of breast cancer. Moreover, rs10995190-GG genotype (P=0.042) and C-G haplotype (P=0.019) revealed a significant association with better overall survival. However, considered polymorphisms and their haplotypes indicated no association with breast density and clinical features of breast cancer. Conclusion: ZNF365 variants might be a potential risk marker of breast cancer in the Iranian population. The interaction between alleles in haplotypes may modulate the amount of the risk conferred by these variants. Further studies on different ethnic groups can validate these results.

A Comparison between Single and Double-Dose Intravenous Ketamine Administration in Bipolar Mood Disorder: A Double-Blind Controlled Clinical Trial.

Objective: As glutamatergic system dysfunction is involved in bipolar depression pathophysiology, the glutamate receptor modulators such as Ketamine have been applied as complementary medication for mood stabilizers. While the treatment is currently just the intravenous injection of a single dose, and there is no robust conclusion on Ketamine effectiveness or its side effects in bipolar patients, this study aimed to consider single- and double-dose intravenous injections of Ketamine in bipolar patients compared to the placebo. Method : In a randomized, double-blind controlled clinical trial, 30 patients diagnosed with bipolar I and II disorders according to DSM-IV-TR (SCID-I) were randomly divided into three groups: the first group received an intravenous injection of Ketamine (0.5 mg/kg) and placebo with a three-day interval, the second group received two doses of Ketamine (0.5 mg/kg) in the same interval, and the third group received two placebo injections. Patients were assessed for depression, anxiety, and mania at various time points, including before the injection, 60 minutes after the injection, on the first, third, fifth, seventh, and 14th day, as well as at the end of the first month using the Hamilton Depression Rating Scale, Beck Anxiety Inventory, and Young Mania Scale, respectively. Data were analyzed using ANOVA and Repeated measure tests. Results: The mean age of patients was 36.8 ± 7.9 years, with 18 females (60%) and 12 (40%) males. Depression and anxiety showed significant differences in both the single- and double-dose Ketamine groups over time (P < 0.01). Moreover, mania displayed significant changes during the study time in the single- and double-dose Ketamine groups, as well as the in the control group. However, during the study time, there were no significant differences observed in depression, anxiety, and mania among the three groups (P = 0.198, P = 0.416, and P = 0.540, respectively). Patients did not indicate any side effects during the study. Conclusion: Intravenous Ketamine administration may relieve depressive manifestations in bipolar patients. The findings suggest that a double dose of Ketamine does not lead to greater improvement than a single dose.

Genetic contribution of caspase-8 variants and haplotypes to breast cancer risk and prognosis: a case-control study in Iran.

PURPOSE: Multiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population. METHODS: In a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR. RESULTS: rs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32-2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23-0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14-0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02-0.43)]. CONCLUSION: The present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.

The Effect of Adding Curcumin to Sertraline in the Treatment of Severe Major Depressive Disorder: A Randomized, Double-Blind Clinical Trial.

OBJECTIVES: Major depressive disorder (MDD) is a chronic and debilitating disease influenced by inflammatory processes in the brain. Some evidence has represented the adding curcumin as a complementary regime to the standard medication in treating depressive symptoms. However, limited clinical trials have been conducted on the antidepressants effects of curcumin in MDD patients. Therefore, this study aimed to investigate the effectiveness of curcumin in the treatment of MDD. METHODS: In a randomized, double-blind clinical trial, 45 severe MDD patients referred to the psychiatric clinic of Ibn-e-Sina Hospital, Mashhad, Iran, during 2016 were selected. Patients were randomly divided into 2 groups who received sertraline plus curcumin or placebo at a dose of 40 mg/d for 8 weeks. The patients were evaluated using Beck Anxiety and Depression Surveys at the beginning of the study, fourth, and eighth weeks by a psychiatry resident. The data analyzed aiding SPSS software. RESULTS: While depression and anxiety significantly decreased during the 8 weeks of the study, there was no significant difference between the 2 groups (P > 0.05). However, the anxiety score was lower in the intervention group. Moreover, no severe adverse events were observed in all patients. CONCLUSIONS: Adding 40 mg/d of SinaCurcumin to sertraline as a routine medical regimen did not improve the depression and anxiety levels in severe MDD patients. However, the anxiety score was lower in the intervention group than in the placebo receiver, which suggests curcumin may have a more effect on anxiety.

Genetic architecture of mammographic density as a risk factor for breast cancer: a systematic review.

BACKGROUND: Mammography Density (MD) is a potential risk marker that is influenced by genetic polymorphisms and can subsequently modulate the risk of breast cancer. This qualitative systematic review summarizes the genes and biological pathways involved in breast density and discusses the potential clinical implications in view of the genetic risk profile for breast density. METHODS: The terms related to "Common genetic variations" and "Breast density" were searched in Scopus, PubMed, and Web of Science databases. Gene pathways analysis and assessment of protein interactions were also performed. RESULTS: Eighty-six studies including 111 genes, reported a significant association between mammographic density in different populations. ESR1, IGF1, IGFBP3, and ZNF365 were the most prevalent genes. Moreover, estrogen metabolism, signal transduction, and prolactin signaling pathways were significantly related to the associated genes. Mammography density was an associated phenotype, and eight out of 111 genes, including COMT, CYP19A1, CYP1B1, ESR1, IGF1, IGFBP1, IGFBP3, and LSP1, were modifiers of this trait. CONCLUSION: Genes involved in developmental processes and the evolution of secondary sexual traits play an important role in determining mammographic density. Due to the effect of breast tissue density on the risk of breast cancer, these genes may also be associated with breast cancer risk.

2q35-rs13387042 variant and the risk of breast cancer: a case-control study.

BACKGROUND: Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease etiology. According to Genome-wide association studies, some single-nucleotide polymorphisms such as 2q35-rs13387042-(G/A) have been introduced to be associated with breast cancer risk and features. In this study, we aimed to evaluate the association between this variant and the risk of breast cancer in a cohort of Iranian women. METHODS: Demographics and clinical information were collected by interview and using patients' medical records, respectively. DNA was extracted from 506 blood samples, including 184 patients and 322 controls, and genotyping was performed using allele specific-PCR. SPSS v16 was used for statistical analysis. RESULT: Statistically significant association was observed between AA genotype and disease risk in all patients [padj = 0.048; ORadj = 2.13, 95% CI (1.01-4.50)] and also ER-positive breast cancers [padj = 0.015; ORadj = 2.12, 95% CI (1.16-3.88)]. There was no association between rs13387042 and histopathological characteristics of the disease. Furthermore, overall survival was not statistically associated with genotype and allelic models even after adjustment for stage and receptor status (p > 0.05). CONCLUSION: There is a statistically significant association between 2q35-rs13387042 and breast cancer risk. rs13387042-AA genotype might be a risk-conferring factor for breast cancer development in the Iranian population. However, further consideration is suggested to confirm its role in risk assessment and probable association with other genetic markers.

Oxcarbazepine versus sodium valproate in treatment of acute mania: a double-blind randomized clinical trial.

Oxcarbazepine as an anticonvulsant has been suggested as an effective drug in affective disorders. The present study was designed to compare the efficacy of oxcarbazepine and sodium valproate in the treatment of acute mania in the Iranian population. In a double-blind, randomized clinical trial, hospitalized bipolar patients in the acute manic phase who were admitted to Ibn-e-Sina psychiatric hospital in Mashhad city (north-eastern part of Iran) were enrolled. The diagnosis was confirmed using Structured Clinical Interview for DSM-IV-TR. Patients were then randomly allocated into two groups taking oxcarbazepine (900-2400 mg/day) and sodium valproate (about 20 mg/kg/day) for 6 weeks. Young Mania Rating Scale (YMRS), Clinical Global Impression Scale (CGI-S), and adverse effects of drugs were assessed at baseline and after 3 and 6 weeks. Mania symptoms based on mean scores of YMRS and CGI-S significantly decreased from baseline to endpoint in both treatments (P < 0.01). However, there was no significant difference between the two groups in terms of reduction of symptoms during times (P = 0.715 and P = 0.446, respectively) and adverse events (P > 0.05). This study confirmed the previous findings that indicate the efficacy of oxcarbazepine as same as sodium valproate. Moreover, its adverse effects resemble sodium valproate in the treatment of acutely manic patients.

The Effect of Krocina™ on Decreasing Substance User Withdrawal Syndrome, Craving, Depression and Stress: A Double-Blind Randomized Parallel Clinical Trial.

INTRODUCTION: Due to the association between substance use abstinence with some psychological syndromes, the use of herbal medicines such as Crocus sativus L. have been considered as a proper approach to controlling withdrawal syndrome. The present study aimed to identify the effect of Krocina™ in reducing withdrawal symptoms, craving, depression, stress, anxiety and durability of treatment in the detoxification period and abstinence phase. METHODS: In a double-blind randomized parallel clinical trial, 72 opioid users passing the detoxification period who were referred to the Soroush Center during 2020, randomly categorized into the two groups. Motivational interviewing sessions and 15 mg of Krocina™ twice a day were provided for six weeks for the cases. The placebo group received pills with the same coating and motivational interviewing. Withdrawal symptoms, craving, depression, stress and anxiety were assessed at the start of the study and then weekly using the Clinical Opiate Withdrawal Scale, Obsessive-Compulsive Drug Use Scale, and the Depression Anxiety Stress Scales-21, respectively. SPSS-v16 was used for statistical analyses. RESULTS: Drug withdrawal symptoms and craving did not indicate a significant difference by Krocina™ intervention during the time (p > 0.05). Furthermore, depression, stress and anxiety were statistically similar between Krocina™ and placebo groups (p > 0.05). Moreover, we found similar findings between the two groups when analyzing only patients with negative urinary test (F = 0.03;p = 0.86). CONCLUSION: Our finding rejected the effectiveness of 30 mg/day of Krocina™ for six weeks as an effective substance for decreasing withdrawal symptoms, craving, depression, anxiety and stress at the detoxification period and abstinence phase.

Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk.

PURPOSE: Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between SMAD7 gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer. METHODS AND MATERIALS: This study was designed as a case-control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants: rs4939827, rs34007497, rs8085824 and rs8088297 were genotyped using ARMS-PCR method. RESULTS: SMAD7 rs4939827 in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38-6.09), p = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00-2.75), p = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk. CONCLUSION: Based on the identified association of SMAD7 gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-ß.

Evaluating the Association between CCR5delta32 Polymorphism (rs333) and the Risk of Breast Cancer in a Cohort of Iranian Population.

BACKGROUND: CC chemokine receptor 5 (CCR5) is introduced as an immune response modulator. The activity of CCR5 influences breast tumour development in a p53-dependent manner. This study aimed to investigate the frequency of CCR5delta32 and its association with the risk of breast cancer in 1038 blood samples in North East of Iran. METHODS: In this case-control study, we genotyped 570 control samples and 468 breast cancer patients by a gel electrophoresis-based gap-polymerase chain reaction (gap-PCR) method Mashhad, Iran. The data were analyzed using the SPSS software. RESULTS: Of 570 controls included, 542 (95.09%) had CCR5delta32 wild/wild (W/W) genotype, 28 samples (4.91%) had CCR5delta32 wild/deletion (W/D) genotype and none of them were CCR5delta32 deletion/deletion (D/D) genotype (0%). While 428 samples of patients (91.45%) had CCR5delta32 W/W genotype, 40 samples (8.55%) had CCR5delta32 W/D and CCR5delta32 D/D homozygous was nil (0%) amongst cases. All samples were in the Hardy-Weinberg equilibrium (P>0.05). According to the allele frequency, D allele, as a risky allele, in the cases was more than the control samples (0.0427 vs 0.0245, respectively) (P=0.0206). Hence, W/D genotype may confer a risk effect (OR=1.77, CI: 1.09-2.90; P=0.0206) compared with WW genotype between case and control groups. CONCLUSION: There is a statistically significant association between CCR5W/D and breast cancer risk. CCR5 may be regarded as a target for the prevention of breast cancer in certain conditions such as interaction with p53 variants, which remains to be further investigated.

The impact of CYP19A1 variants and haplotypes on breast cancer risk, clinicopathological features and prognosis.

BACKGROUND: Different genetic variants in hormone-regulating pathways have been identified to influence the risk of breast cancer. This study aimed to evaluate the association of CYP19A1 rs10046 and rs700519 polymorphisms with the risk, clinicopathological factors and prognosis of breast cancer. METHODS: In a case-control study, rs10046 and rs700519 polymorphisms were genotyped using ARMS-PCR and high-resolution melting (HRM), respectively, in a total of 702 females. Statistical analysis and evaluation of haplotypes and linkage disequilibrium were performed using SPSS v16, PHASE and 2LD. RESULTS: Although no association of rs700519 with breast cancer was observed, rs10046 in different genetic models as well as C-C/C-T and C-C/C-C diplotypes, revealed the association with the risk of breast cancer (p < 0.05). Moreover, the rs700519-C allele was shown to be associated with longer overall survival. In contrast, the T-T haplotype conferred s a shorter overall survival. rs700519-C allele was also significantly associated with menarche age. CONCLUSION: Based on the identified independent association between CYP19A1 diplotypes and rs700519-C allele with the risk and prognosis of the disease, the gene region and its genetic variants may have a diagnostic and prognostic role in breast cancer development. Further confirmation using other variants in this locus can validate these findings.

Therapeutic role of extracellular vesicles derived from stem cells in cutaneous wound models: A systematic review.

A growing body of evidence has shown that extracellular vesicles can be efficient as experimental therapeutics in pre-clinical models of skin wounds, but there is a significant unmet need to translate this to clinical utilization. The objectives of the current systematic review were to identify the strength of the therapeutic effects of EVs derived from stem cells in cutaneous wounds and to assess which EV-mediated mechanisms could be involved in the therapeutic response. PubMed, ISI Web of Science, and Scopus databases were systematically searched. We retrieved English-language articles published through June 2020. In vivo studies which applied stem cell-derived EVs were included for further analysis. The Risk of bias was assessed by the SYRCLE tool. We identified thirty-nine pre-clinical studies that evaluated the effects of EVs on the wound healing process. The included studies varied greatly in EVs isolation techniques, route of administration, EVs producing cells, and follow-up time. In vivo application revealed beneficial effects of EVs on accelerating wound closure and re-epithelialization in a dose-dependent manner. Elevated angiogenesis was reported in twelve eligible studies through multiple signaling pathways such as PI3K/Akt, MAPK/ERK, and JAK/STAT. The well-known signaling pathway to inhibit scar formation was TGF-ß2/SMAD2. However, all included studies were not blinded enough which may have introduced bias. Therefore, the transition of EV's efficacy into the clinics is deeply rooted in the following important factors: 1) pre-clinical studies with a lower risk of bias and longer follow-up time, and 2) consistent, reproducible, and feasible manufacturing of EVs production in a large-scale commercial program.

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients.

The effect of somatic mutations and the gene expression profiles on the prognosis is well documented in cancer research. This study was conducted to evaluate the association of GATA3 somatic mutations with tumor features, survival, and expression profiles in breast cancer. Clinicopathological information was compared between TCGA-BRCA patients with GATA3-mutant and non-mutant tumors in all patients as well as in ER-positive subgroup. Cox-regression method was used to evaluate the association of the GATA3 mutation status with overall survival time. Differential gene expression, functional annotation, and protein-protein interaction analyses were performed using edgeR, Metascape, DAVID, STRING and CytoNCA. GATA3-mutant and non-mutant samples had significantly different clinicopathological features (p < 0.05). While GATA3 mutation status was not associated with the overall survival in the entire cohort (padj = 0.52), the GATA3-wild type ER-positive cases had a better prognosis than mutant ones (padj = 0.04). GATA3 expression was higher in tumors than normal tissues. Several pathways were different between mutant and non-mutant groups (p < 0.05). Interleukin-6 was found as the highest scored gene in both comparisons (normal vs. mutant and normal vs. non-mutant groups) in the entire patient and in the ER-positive subgroup, suggesting the association of IL6 with breast tumorigenesis. These findings suggest that GATA3 mutations can be associated with several tumor characteristics and influence the pattern of gene expression. However, GATA3 mutation status seems to be a prognostic factor for the disease only in ER-positive patients.

Prevalence of Respiratory Disorders during Sleep among Subjects of Methadone Maintenance Therapy Program.

BACKGROUND: Respiratory disorders during sleep are considered a health problem affecting the life quality. There is some evidence indicating the higher prevalence of apnea in substance-dependent patients. However, there is no information on the prevalence of the disease in people under methadone maintenance therapy (MMT). Therefore, the present study was designed to estimate the disease rate in these patients and consider the relationship of the increasing risk of apnea with some psychiatric problems. METHODS: Study group included 152 individuals under the MMT program. Baseline data were collected with the interview, and patients were considered using the STOP-BANG questionnaire to evaluate the risk of apnea. Furthermore, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HDRS) tests were performed for all participants. Data were analyzed using SPSS software. FINDINGS: Based on the STOP-BANG score categories, 37.5%, 40.1%, and 22.4% of patients indicated low, intermediate, and high risk of apnea, respectively. Moreover, severe daytime sleepiness, fatigue, depression, and anxiety were observed in 5.3%, 5.5%, 6.0%, and 21.1% of participants, respectively. Sex (P = 0.007) and daytime sleepiness (P = 0.048) were significantly different between low and high-risk groups of apnea after adjustment. Besides, age (P < 0.001) and fatigue (P = 0.007) were factors predicting the STOP-BANG score. CONCLUSION: These findings revealed the higher prevalence of apnea in MMT patients compared to the general population of Iran and rising of the risk of apnea along with an increase in age and fatigue score. However, attention to the sleep disorders in MMT is a prominent factor that should be considered as a route of therapy.

ESR1 gene variants, haplotypes and diplotypes may influence the risk of breast cancer and mammographic density.

Breast cancer as the most common cancer worldwide is influenced by genetic and physiological factors. Based on some evidence indicating the role of estrogen receptor 1 gene (ESR1) in breast cancer development, in this study, the association of three common variations in ESR1 gene with breast cancer and density in an Iranian population was evaluated. In a case-control study, 400 blood samples were collected for DNA extraction and genotyping. Breast density was assessed using mammography. ESR1 rs6915267 (G/A), rs2077647 (C/T) and rs1801132 (C/G) were genotyped using ARMS-PCR method. PHASE program was used to estimate the haplotypes frequencies. Our data analysis showed rs6915267 GA genotype in the heterozygous (GA) as well as co-dominant models was associated with lower mammographic density. None of the three variations were associated with the breast cancer risk. Haplotype analysis indicated G-T-C haplotype of rs6915267, rs2077647 and rs1801132 [OR = 0.54, 95% CI (0.31-0.92), p = 0.025] and G-T/G-T diplotype of rs6915267-rs2077647 [OR = 0.38, 95% CI (0.17-0.86), p = 0.019] were associated with a decreased risk of breast cancer. ESR1 may affect density of the breast and its haplotypes may modulate breast cancer risk.

The Dilemma of TP53 Codon 72 Polymorphism (rs1042522) and Breast Cancer Risk: A Case-Control Study and Meta-Analysis in The Iranian Population.

OBJECTIVE: Mutations of TP53 as a tumor suppressor gene are frequently observed in different types of cancer. A codon 72 polymorphism located on exon 4 with two alleles encoding either Proline (CCC) or Arginine (CGC) has been indicated as a common variation in association with cancers. Controversial results have been reported regarding the association of allelic polymorphism of codon 72 of TP53 gene and breast cancer risk in Iranian patients. Therefore, a case-control study was designed. A meta-analysis was also carried out to provide evidence of association between this variation and breast cancer in Iran, based on all available published data. MATERIALS AND METHODS: In this case-control study, blood sample of 622 participants, including 308 breast cancer cases and 314 controls were collected. Genotyping for rs1042522 was conducted by Allele Specific polymerase chain reaction (AS-PCR). In order to set a meta-analysis study, PubMed, Scopus and ISI Web of Knowledge and Persian databases were searched to explore relevant studies, published up to September 2018, containing information on TP53 polymorphism and the risk of breast cancer in Iran. Statistical analysis was performed using SPSS 16.0 and MetaGenyo. RESULTS: All retrieved available data as well as the results of our current study were consisted of 1965 breast cancer cases and 1999 healthy controls. No significant difference was observed in allele frequencies between groups (P=0.90) in our study. The cumulative results did not also show any association between rs1042522 and breast cancer risk on the dominant (P=0.61) and recessive (P=0.89) models. CONCLUSION: These findings cannot support contribution of rs1042522 polymorphism to breast cancer risk in an Iranian population. Future larger studies may help confirm this finding with a greater power.

The Impact of CASP8 rs10931936 and rs1045485 Polymorphisms as well as the Haplotypes on Breast Cancer Risk: A Case-Control Study.

INTRODUCTION: Single nucleotide polymorphisms account for most genetic predispositions to breast cancer in the general population. Because of the lack of studies concerning the 2 common polymorphisms in caspase 8 (CASP8), namely rs104548 and rs10931936 in Iranian population, we evaluated the association of these 2 polymorphisms and their haplotypes with breast cancer and molecular profile. MATERIALS AND METHOD: Blood samples were collected from 287 breast cancer patients and 490 controls. Genotyping of rs1045485 and rs10931936 was conducted using an amplification refractory mutation system and polymerase chain reaction restriction fragment length polymorphism, respectively. PHASE version 2 (Matthew Stephens) was used to estimate the frequencies of haplotypes. Statistical analysis was performed using SPSS 16.0 (SPSS Inc). RESULTS: Although hormone receptors and the molecular profile did not indicate any significant association with different genotypes (P > .05), patients with CC genotype of rs1045485 were more likely to have HER2-positive breast cancer than those with GG genotype (odds ratio [OR], 2.93; 95% confidence interval [CI], 1.0 4-8.26). In addition, CC genotype of D302H was associated with a decreased risk of breast cancer to 48% (OR, 0.52; 95% CI, 0.30-0.90) whereas no significant association was found between rs10931936 and breast cancer. Haplotype analysis indicated C-C haplotype is associated with the decreased risk of breast cancer (OR, 0.69; 95% CI, 0.52-0.91). CONCLUSION: Our data showed a protective effect for CC genotype of rs1045485 variant and C-C haplotype of rs10931936-rs104548 in CASP8 in association with the decrease risk of breast cancer whereas rs10931936 showed no significant association. CASP8 rs1045485 polymorphism might be a candidate genetic marker to evaluate risk of breast cancer. However, further larger studies can confirm such findings.