A prospective population-based study of stroke in the Central Region of Iran: The Qom Incidence of Stroke Study.

OBJECTIVE: Based on the few population-based studies that have been conducted in the Middle East, we determined the incidence of stroke in Qom, one of the central provinces of Iran. METHODS: The Qom province includes an estimated at-risk population of about 1 million. During a 12-month period (November 2018-November 2019), all first-ever strokes occurring in the target population were registered. Hospitalized cases were ascertained by discharge codes. Out-of-hospital cases were ascertained by a prospective screening of emergency medical services, emergency departments, ambulances records, primary care clinics, rural and urban public health centers, primary care physician offices, and neurologists' offices. Crude and age-adjusted incidence rates (per 100,000 person-years) were calculated. RESULTS: During the study period, 1462 first-ever strokes occurred with a mean age of 68.1 (17-103) years; of these 45.2% were females (661 cases). The crude annual incidence rate per 100,000 at-risk populations was 145.4 (95% confidence interval, 138.1-153.0) for all types of stroke (156.5 for males and 134.3 for females), 26.4 (95% confidence interval, 23.5-29.8) for hemorrhagic stroke, and 114 (95% confidence interval, 105-121) for ischemic stroke. The incidence rate adjusted to the world population was 201.4 (95% confidence interval, 193-210) per 100,000 at-risk populations (adj incidence, 218.5 for males vs 187.4 for females). The total fatality rate during the first 28 days was 19.6%. CONCLUSION: This study states that in this region there is a high incidence of stroke, which occurs at a younger age than the global average. There was a high prevalence of underlying stroke risk factors.

CYP17 MspA1 Gene Polymorphism and Breast Cancer Patients According to Age of Onset in Cancer Institute of Iran.

BACKGROUND: Exposure to endogenous hormones such as estrogen is known as a lifetime Breast Cancer (BC) risk factor. Polymorphisms in genes that are involved in the steroidogenic process, such as Cytochrome P450c17alpha (CYP17), affect individuals' susceptibility to BC. In Iran, the highest incident of BC is among young women. This study aimed to find prevalence of Single Nucleotide Polymorphisms (SNPs) in genes such as CYP17 and significant correlation with age-oriented group of breast cancer. METHODS: In 2016, a case series study was conducted on a total population of 205 patients suffering from breast cancer referred to Cancer Institute, Imam Khomeini Hospital Complex, Tehran, Iran. This population consisted of 104 cases less than 40 yr old and 101 cases over 40. The genotype variants of CYP17 MspA1 were determined using PCR, followed by RFLP. The association of CYP17 MspA1 polymorphisms with the risk of BC in two different age groups was evaluated by calculating odds ratio and 95% confidence intervals using unconditional logistic regression. RESULTS: Carriers of at least one A2 allele may have higher risk of developing breast cancer at younger age compared to patients with A1/A1 genotype (Odds Ratio: 1.99, 95% Confidence Interval: 1.11-3.57, P=0.02). CONCLUSION: CYP17gene polymorphisms may have influence on the early onset of breast cancer.

HLA-DRB1 does not have a role in clinical response to interferon-beta among Iranian multiple sclerosis patients.

BACKGROUND & OBJECTIVES: The role of human leukocyte antigen (HLA) in clinical response to immunotherapy is not completely known. In this study we evaluated the relationship between HLA-DRB1 genotype, which has been proved to be more common in Iranian MS patients, and clinical response to interferon-beta (IFNß), which is the most common immunotherapy for relapsing-remitting MS. DESIGN AND SETTING: In this study 68 Iranian patients with confirmed diagnosis of RRMS who had been referred to and admitted in Neurology Department of Amiralam and Khatam Hospitals in Tehran were selected. Patients were followed prospectively for 2 years since initiation of therapy and clinical data, including EDSS scores were recorded every 3 months. MRI was performed at the time of diagnosis and each year. METHODS: HLA-DRB1 typing was performed by polymerase chain reaction (PCR) for all patients and data was analyzed by STATA 12th edition. RESULTS: There were 47 (69.1%) responders and 21 (30.9%) non-responders. These two groups were demographically and clinically comparable. Fisher's exact test did not show any difference between HLA-DRB1 allele frequencies in responders and non-responders. CONCLUSIONS: Our findings confirmed the lack of association between HLA-DRB1 and clinical response to IFNß among MS patients as previous studies had done.

Relationship between HLA-DRB1* 11/15 genotype and susceptibility to multiple sclerosis in Iran.

BACKGROUND & OBJECTIVES: Analysis of the role of different alleles of human leukocyte antigen (HLA) in multiple sclerosis (MS) patients is necessary in many populations and geographical areas. The aim of the present study was to investigate the frequency of HLA-DRB1 genes and its influence on susceptibility to MS, comparing with that in control group. DESIGN AND SETTING: Two groups of case-control of multiple sclerosis patients referred to clinic at Khatam hospitals were studied. The first group consisted of 73 multiple sclerosis patients and the second group comprised 40 healthy volunteers with no known history of MS, living in Tehran. PATIENTS AND METHODS: The sample population consisted of 73 consecutive non-selected patients diagnosed with MS according to the McDonald criteria (2010) at the outpatient clinic for multiple sclerosis, 62 (85%) presented with RRMS and 11 (15%) with SPMS. The frequency of HLA-DRB1 alleles was determined in 73 MS patients (with age of 18-56) and 40 healthy subjects in Iran. These consisted of 57 females and 16 males. HLA-DRB1 allele types were identified by polymerase chain reaction products of 24 pair primers for low resolution SSP typing (PCR-SSP). RESULTS: The HLA-DRB1* 11/15 genotype was detected highest (6 times) in patients compare to normal control population (p-value 0.062), whereas the DRB1 4/11 genotype was detected highest (4 times) in controls compare to MS patients (p-value 0.033). The data showed that HLA-DRB1*03 is significantly more in patients compare to control normal people (p-value 0.0021) as well as DRB1 14 and 16 are significantly more in control normal people, compare to MS patients (p-values 0.0789 and 0.035). CONCLUSION: Allele frequency among patients with positive history of multiple sclerosis disease showed that DRB1 11 allele has a significantly low rate in MS patients with positive history compare to other patients. In contrast DRB1 15 allele has a significantly high rate in MS patients with positive history compare to other patients. The frequencies of other alleles were not significantly different between the MS patients and the control group. The frequency of the HLA-DRB1* 11/15 genotype detected in the present study showed that this genotype is partially significant factor for MS susceptibility and development in Iran.

A registry program for familial gastric cancer patients referred to Cancer Institute of Iran.

BACKGROUND: Gastric cancer is the second most common cause of cancer death. It has a poor prognosis with only 5-10% of hereditary etiology. If it is diagnosed, it could be helpful for screening the other susceptible members of a family for preventive procedures. Usually it is identified by symptoms such as presence of cancer in different members of family, some special type of pathology such as diffused adenocarcinoma, having younger age and multiple cancer syndromes. Hence, designing a registry program can be a more practical way to screen high risk families for a preventive program. MATERIALS AND METHODS: Based on the inclusion criteria, a questionnaire was prepared. After pilot on a small number of patients, the actual data was collected from 197 patients and processed in SPSS 16.0. RESULTS: Totally, 11.8% of the patients were younger than 45 years old. Blood type 'A' was dominant and males had a higher risk behavior with higher consumption of unhealthy food. Adenocarcinoma was reported in majority of cases. 21.8% of the patients had the including criteria for familial gastric cancer (FGC). CONCLUSIONS: The high percentage of FGC population compared to the other studies have revealed a need to design an infrastructural diagnostic protocol and screening program for patients with FGC, plus preventive program for family members at risk which could be done by a precise survey related to frequency and founder mutations of FGC in a national registry program.

Familial breast cancer registry program in patients referred to the cancer institute of Iran.

INTRODUCTION: Annually a considerable number of people die because of breast cancer, a common disease among women also in Iran. Identifying risk factors and susceptible people can lead to prevention or at least early diagnosis. Among susceptibility risks, 5-10% of patients have a family history predisposing factor which can influence the risk of incidence among the family. Having a registry program can be a more practical way to screen high risk families for preventive planning. METHOD: Based on inclusion criteria, a questionnaire was prepared and after a pilot study on a small number of patients, actual data were collected on 400 patients and processed in SPSS 16.0. RESULTS: Totally, 28.2%of the patients were younger than 40 years old and 36.8% had the included criteria for familial breast cancer (FBC). 102 patient's samples could be compared for receptor presentation. Similar to other studies, the number of triple negative breast cancers increased as the age decreased. CONCLUSION: The high percentage of patients with FBC among 400 cases in this study demonstrates that in order to design an infrastructural diagnostic protocol and screening of patients with FBC, a precise survey related to frequency and founder mutations of FBC is needed nationwide.

Her2 amplification status in Iranian breast cancer patients: comparison of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH).

INTRODUCTION: Her2/neu is a biomarker which is amplified and/or overexpressed in a subset of breast cancer patients who are eligible to receive trastuzumab. Her-2 gene amplification analysed by fluorescence in situ hybridisation (FISH) and/or protein over-expression detected by immunohistochemistry (IHC) are the two main methods used to detect Her-2 status in clinical practice. The concordance rate between the two techniques is controversial. METHODS: FISH analysis were performed on 104 tumoural samples from breast cancer patients with known IHC results to determine the Her2 gene status. The FISH/IHC analyses results were then compared and the concordance rate was determined. RESULTS: Her2 gene amplification was detected in 0 of IHC score 1+, 24/86 (27.91%) 2+, and 8/13 (61.54%) 3+. The IHC and FISH results concordance rates were 100%, 27.9%, and 61.5% for IHC scores of 1+, 2+, and 3+ respectively. CONCLUSION: The results of this study suggest that IHC 1+ should be considered as negative while IHC 2+ results need further confirmative analysis by FISH. Further quality control and standardization of IHC technique are required to improve the concordance rate between the two methods.

Comparative genomic hybridization (CGH) analysis of chromosomal aberrations in Iranian patients with invasive ductal carcinoma breast cancer.

INTRODUCTION: Breast cancer is one of the most common cancers in women; however, due to the complexity of chromosomal changes, limited data are available regarding chromosomal constitution. MATERIALS AND METHODS: In this study, Comparative Genomic Hybridization (CGH) was used on 16 Iranian patients diagnosed with invasive ductal breast carcinomas. RESULTS: 12 samples had abnormal CGH results (75%), including 21 types of chromosomal imbalance. The most prevalent were chromosomal gain of +1q, +17q, +8q and chromosomal loss of -13q. All three cases with DNA loss at chromosome 13q (-13q) had lymph node metastasis. CONCLUSIONS: CGH is able to detect chromosomal abnormalities which are difficult to identify by conventional cytogenetic techniques. More studies on a larger sample size may help to confirm or rule out any possible correlation between 13q monosomy and lymph node metastasis, which could result in establishing new strategies for prevention and early detection of invasive breast tumors.

Determination of human papillomavirus type 16 genotype and construction of cloning vector pTZ57R encoding HPV16 E7 gene.

OBJECTIVE: To isolate and construct a cloning vector containing the human papillomavirus (HPV)16-E7 gene as a target for application as a DNA vaccine. METHODS: The study was performed in 2005 in Iran. The E7 gene, one of the most important HPV oncoproteins and a target molecule for therapeutic vaccines, was amplified by polymerase chain reaction (PCR). The PCR product was cloned into a suitable cloning vector and confirmed by colony-PCR, restriction enzyme analysis, and sequenced. RESULTS: The desired plasmid was sequenced and indicated 99% homology with those mentioned in the Genbank. CONCLUSION: The Iranian HPV16 E7 gene sequence is very similar to other sequences in the Genbank, and it can be used as a candidate gene in a therapeutic vaccine for Iranian patients with cervical cancer.

Combining mammaglobin and carcinoembryonic mRNA markers for early detection of micrometastases from breast cancers--a molecular study of 59 patients.

INTRODUCTION: As many as 30% of node-negative breast cancer patients relapse within five years, suggesting that current histological detection methods are inadequate for identifying metastatic disease. Detecting small number of cancer cells in the breast tissue or lymph node by reverse transcription-polymerase chain reaction (RT-PCR) assays using a combination of tissue and cancer specific markers might be very useful in the early detection or monitoring of the treatment. Mammaglobin is a member of the uteroglobin gene family and appears to be expressed only in breast tissue. Carcinoembryonic antigen has been the preferred molecular marker for detection of micro metastases in lymph nodes in almost all carcinomas. MATERIALS AND METHODS: Samples were collected from randomly chosen breast cancer patients undergoing modified mastectomy or breast conserving surgery between September 2003 and July 2004. RT-PCR was applied to study the expression of MMG and CEA markers. Breast cancer micrometastases in axillary lymph nodes were also assessed. RESULTS: The MMG marker was positive in 9/10 normal breast tissues, 3/3 breast fibroadenomas and 37/39 of breast carcinoma tissues, giving an overall sensitivity of 94%. The sensitivity was 80% for metastatic lymph node samples. On the other hand CEA showed 95% sensitivity for malignant breast tumors and 100% sensitivity for metastatic lymph nodes. CONCLUSIONS: RT-PCR using a combination of MMG and CEA markers is a powerful tool to complement current routine histopathology techniques for detection of breast cancer metastasis in axillary nodes.

Prevalence of human papillomavirus genotypes in women with normal and abnormal cervical cytology in Iran.

INTRODUCTION: HPV infection has a prime etiologic role in development and progression of cervical cancer, one of the most frequent forms of cancer among women in developing countries. This study was designed to determine the most prevalent HPV genotypes in women with normal and abnormal cervical cytology in Iran. MATERIALS AND METHODS: Samples from134 patients, including 127 who attended gynecology clinics and 7 with solid cervical tumors were used. All 127 patients underwent routine Pap tests for cytological evaluation and at the same visit a sample of cervical epithelial cells was obtained by scraping the cervix osteum. In each case HPV infection was primarily evaluated by PCR using GP 5/6 primers and then subtyping was performed in proved infected samples with specific primers for HPV 16, 18, 31, 33, 11 and 6. After cytological evaluation, 50 patients with abnormal Pap tests were categorized as the abnormal group and the remaining 77 patients as the normal group. RESULTS: In the normal group, HPV infection was established in 10 cases (13% infection rate), while 30 HPV positive cases were discovered in the abnormal group (60% infected). The most prevalent genotypes among the infected samples were HPV 16 (76%), HPV18 (12.7%) and HPV11/6 (8.5%). Moreover, all 7 tumor samples were positive for HPV general primers of which, 5 samples were infected with HPV 16, two were co-infected with HPV16,18 and HPV16,31 genotypes and one was infected with HPV 18. CONCLUSIONS: Infection with HPV 16 was found to be significantly higher in abnormal group in comparison with normal group (42% vs. 11.6%, P value <0.005), likewise HPV18 genotypes were proved to be more prevalent in abnormal group (8% vs. 0%, P value <0.05). No significant relation between other HPV genotypes and pathologic cervical changes was obtained. According to our study high rates of infection with HPV genotypes in sexually active Iranian women makes molecular investigation for HPV16 and 18 very essential in clinical approaches to patients with proven dysplasia in their screening tests and also for those patients with borderline (i.e. ASCUS) or incongruous pathology reports. Larger studies are required to determine the most appropriate vaccine with highest protection in Iranian women.