Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene is an inhibitor of apoptosis that expresses in human embryonic tissues but it is absent in most healthy adult tissues. The copy number of BIRC5 has been indicated to be highly increased in tumor tissues; however, its association with the age of onset in breast cancer is not well understood.Forty tumor tissues of breast cancer were obtained from Tumor Bank of Cancer Institute, Imam Khomeini Hospital, Tehran, Iran. BIRC5 gene copy number variation (CNV) was evaluated using Multiplex Ligation-dependent Probe Amplification (MLPA) and then compared with the age of onset for each patient.BIRC5 amplification was seen in 17.5% of cases. Also, a significant association was observed between BIRC5 gene amplification and individuals under 40 years of age (P=0.04).BIRC5 gene has the potential to be a marker for the detection and prognosis of cancer at an early age.
Background: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study. Methods: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected. Results: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls. Conclusion: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum.
Site-directed mutagenesis is a fundamental tool indispensable for protein and plasmid engineering. An important technological question is how to achieve the efficiency at the ideal level of 100%. Based on complementary primer pairs, the QuickChange method has been widely used, but it requires significant improvements due to its low efficiency and frequent unwanted mutations. An alternative and innovative strategy is to utilize primer pairs with 3-prime overhangs, but this approach has not been fully developed. As the first step towards reaching the efficiency of 100%, we have optimized this pproach systematically and evaluated the resulting method extensively with >100 mutations on 12 mammalian expression vectors, ranging from 7.0-13.4 kb in size and encoding ten epigenetic regulators with links to cancer and neurodevelopmental disorders. We have also tested the new method with two expression vectors for the SARS-COV-2 spike protein. Compared to the QuickChange method, the success rate has increased substantially, with an average efficiency of >50%, with some at or close to 100%, and requiring much less time for engineering various mutations. Therefore, in this study, we have developed a new site-directed mutagenesis method for efficient, versatile and economical generation of various mutations. Importantly, the extensive experience from this study also sheds light on how to develop ideal mutagenesis methods with the efficiency at or close to 100% for a wide spectrum of plasmids.
Introduction: Iran Familial Breast Cancer Registry (IRFBCR) was established by the Cancer Research Center and Breast Cancer Research Center (BCRC), as the members of the National Cancer Research Network, in 2016.The main purpose of IRFBCR registry is to play a part in patient care by systematic collection, storage, analysis and interpretation of data of patients with familial breast cancer, and to further develop prevention and treatment strategies in regards to familial breast cancer.Methods: Based on the latest international guidelines, different questionnaires have been developed to collect demographics, height and weight, ethnicity, personal history of cancer, medical and surgical history, radiation exposure, smoking and alcohol consumption, menstrual and pregnancy history, breastfeeding, hormone use, and physical activity as well as the patient's tumor tissue characteristics and the treatment that each patient has received in regards to her/his disease.In addition, an informatics center is also being considered for core data collation, management and distribution.Bio-banking of each patient's bio-specimen is also being considered in this project.Results: So far, 20 patients have been recruited and their blood and DNA samples have been saved as a bio-specimen repository. Conclusion:Based on this resource, not only the prevalence of the disease in patients with familial breast cancer in this country can be estimated, but also, it will be a good source for further studies to investigate factors of efficient causes, whether genetic or environmental, contributing in the incidence of familial breast cancer.
Abstract To date, not much study has been done to investigate the mitochondrial DNA (mtDNA) copy number as the potential biomarker for opium exposure. Here, we conducted a cross‐sectional study to determine the relative mtDNA content as the potential biomarker for opium exposure. Quantitative real‐time PCR was performed to investigate the mtDNA copy number variation across 205 individuals, including blood samples of 45 opium users, 41 cigarette users, 47 dual users, and 72 never users of any product. We found a significantly higher mtDNA content among the opium‐only users (adjusted OR: 3.21; 95% CI: [1.34, 7.66]; P = .009) and dual users (adjusted OR: 2.64; 95% CI: [1.15, 6.1]; P = .02) compared to that in never users even after adjustment for confounding factors, age, and sex. Discordantly, analysis of mitochondrial DNA in cigarette smokers revealed an indirect association between cigarette smoking and mtDNA content although it was not statistically significant. The reason behind the increased mitochondrial DNA is unclear. The possible hypothesis is that there might be a way to compensate for the oxidative damage induced by opium consumption. Taken together, our findings indicated that the mtDNA copy number may alter during opium exposure. Since changes in the mitochondrial DNA copy number was associated with the etiology of many diseases including cancer, further investigations on the mtDNA copy number may shed light on the carcinogenicity of opium consumption and means for early detection among the populations who have been exposed to opium and its products.
In this multi-ancestry genome-wide association study (GWAS) and fine mapping study of head and neck squamous cell carcinoma (HNSCC) subsites, we analysed 19,073 cases and 38,857 controls and identified 29 independent novel loci. We provide robust evidence that a 3' UTR variant in
Hearing impairment (HI) caused by mutations in the connexin-26 gene (GJB2) accounts for the majority of cases with inherited, nonsyndromic sensorineural hearing loss. Due to the illegality of the abortion of deaf fetuses in Islamic countries, preimplantation genetic diagnosis (PGD) is a possible solution for afflicted families to have a healthy offspring. This study describes the first use of PGD for GJB2 associated non-syndromic deafness in Iran. GJB2 donor splicing site IVS1+1G>A mutation analysis was performed using Sanger sequencing for a total of 71 Iranian families with at least 1 deaf child diagnosed with non-syndromic deafness. In Vitro Fertilization (IVF) was performed, followed by PGD for a cousin couple with a 50% chance of having an affected child. Bi-allelic pathogenic mutations were found in a total of 12 families (~17 %); of which a couple was a PGD volunteer. The deaf woman in this family was homozygous and her husband was a carrier of the IVS1+1G>A gene mutation. Among 8 biopsied embryos, two healthy embryos were implanted which resulted in a single pregnancy and subsequent birth of a healthy baby boy. This is the first report of a successful application of PGD for hearing loss in Iran. Having a baby with a severe hearing impairment often imposes families with long-term disease burden and heavy therapy costs. Today PGD has provided an opportunity for high-risk individuals to avoid the birth of a deaf child.
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