The Association Between Genetic Variants in ACE1and ACE2 Genes with Susceptibility to COVID-19 Infection.

Angiotensin-converting enzyme 2 (ACE2) receptors facilitate the entry of the causative virus severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) into target cells. Some ACE gene variants have been suggested to be involved in COVID-19 pathogenesis. So, the aim was to assess the association between ACE1 rs4646994 and ACE2 rs2285666 genes polymorphisms and the susceptibility and severity of COVID-19. This case-control study was conducted on 197 patients with COVID-19 and 197 healthy controls. ACE-1 insertion/deletion (I/D) (rs4646994) and ACE2 rs2285666 genes polymorphisms were determined by the amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) technique. The DD genotype of ACE1 I/D polymorphism was associated with increased susceptibility to COVID-19 infection (p = 0.012), whereas the ID genotype of this polymorphism was associated with decreased susceptibility (p = 0.003) (significance level = 0.017). There was no significant association in allele and genotype distribution of ACE2 rs2285666 polymorphism between cases and controls. The ACE1 I/D polymorphism may be considered as a risk factor for COVID-19 susceptibility.

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review.

Background: Head and neck squamous cell carcinomas (HNSCCs) are associated with variable prognosis even with similar clinical characteristics and treatments. Gene polymorphisms have been suggested as prognostic factors for HNSCC which can justified this variable prognosis. So, the aim was to review literatures on gene polymorphisms and prognosis of HNSCCs. Materials and methods: A systematic search was conducted using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases to find all related articles published up to December 2021 in the field of gene polymorphisms and HNSCC prognosis. Results: Of 1029 initial searched articles, 71 articles were selected for inclusion in this systematic review. About 93 genes and 204 polymorphisms have been discussed in these articles. Among the most studied polymorphisms, the XRCC1 Arg399Gln and Arg194Trp polymorphisms were not associated with survival in most studies; the ERCC1 C19007T polymorphism had no significant association in any of the studies. Different gene polymorphisms of glutathione s-transferase family, including GSTM1 deletion, GSTT1 deletion and GSTP1 A313G, were not associated with survival in included studies. There are conflicting results regarding the association between polymorphisms such as ERCC2 A35931C, Asp312Asn, ERCC5 rs1047768 and rs17655 with HNSCC prognosis. Less studied polymorphisms, such as hOGG1 rs1052133 or the VEGF rs699947, were generally not associated with HNSCC prognosis. Conclusion: Reviewed articles reported varied and contradictory results regarding the association of gene polymorphisms and HNSCC prognosis, which necessitates further studies along with meta-analysis on the results of such studies.

Gene polymorphisms and risk of head and neck squamous cell carcinoma: a systematic review.

Background: Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests genetic variation may be a risk factor for the development of HNSCC. So, the aim was to review literatures on the association between gene polymorphisms and risk of HNSCCs. Materials and methods: This systematic review included all articles on the impact of gene polymorphisms on risk and susceptibility to HNSCC published till September 2021 using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases. Results: Of 1163 initial searched articles, 77 articles were eligible to include in this review. Studies were categorized based on gene functions. In each category, studied gene polymorphisms related to growth control genes, cell cycle control, apoptosis, DNA repair genes, carcinogen-metabolizing enzymes, alcohol-metabolizing genes, antioxidant gene, inflammatory cytokine, transcription factor, tumor immunity, folate metabolism, and tumor suppressor gene were discussed separately. Among the polymorphisms that are often significantly associated with HNSCC risk are: GSTM1 null, GSTT1 null, CYP2D6 *4, XRCC1 Arg194Trp and Arg399Gln, ERCC1 C8092A, XPD Lys751Gln, XRCC3 Thr241Met, P53 codon 72 and MTHFR C677T polymorphisms. Conclusion: Varied and contradictory results have been reported in different studies regarding the association of gene polymorphisms with HNSCC risk. To conclude about this association and to overcome these contradictions, it is necessary to use the results of existing meta-analyses or to perform new or updated meta-analyses.

Association between XRCC1 Arg399Gln polymorphism with prognosis of head and neck squamous cell carcinomas: A meta-analysis.

Objective: The X-ray repair cross complementing group 1 (XRCC1) gene is involved in DNA repair. Defects in DNA repair may lead to head and neck squamous cell carcinomas (HNSCCs). Several researches have focused on relationship between XRCC1 Arg399Gln genetic polymorphism with HNSCC's prognosis with conflicting results. So, the aim of the present meta-analysis was evaluation of relationship between XRCC1 Arg399Gln polymorphism with HNSCC's prognosis. Methods: Published articles up to July 2022 were systematically searched through international databases like PubMed, Web of Science, Scopus, etc. I2 test was applied to assess the heterogeneity. Data were analyzed using random effects model. Funnel plots and Egger test were applied for assessing publication biases. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were calculated for evaluation of relationship between the polymorphism with HNSCC's prognosis. Results: Fifteen articles were included for the systematic review. Six of those articles were considered for inclusion in meta-analysis. The different forms of XRCC1 Arg399Gln polymorphism had not significant association with overall survival (OS) under varied genetic models (heterozygous: Ln (HR) = 0.02, 95 % CI= (-0.33,0.37), p-value = 0.90; homozygous: Ln (HR) = 0.33, 95 % CI= (-0.03,0.69), p-value = 0.07 and dominant: Ln (HR) = 0.06, 95 % CI = (-0.17,0.28), p-value = 0.62). Analysis showed that variants of the polymorphism had no significant relationship with OS in Asian and Caucasian ethnicity under dominant model (Ln (HR) = 0.14, 95 % CI= (-0.13,0.40), p-value = 0.31; Ln (HR) = -0.01, 95 % CI= (-0.41,0.38), p-value = 0.96). Conclusion: Different forms of XRCC1 Arg399Gln polymorphism had no significant relationship with HNSCC's prognosis under varied genetic models and based on different ethnicity.

Adenoid Cystic Carcinoma with Intracranial Extension.

Adenoid cystic carcinoma (ADCC) is a malignant tumor of salivary gland origin. ADCC of sinonasal tract is rare. We present a rare and unresectable case of sinonasal ADCC with intracranial extension in an 83-year-old man with the chief complaint of nasal congestion. Invasion to the maxillary sinus, nasopharynx, anterior cranial fossa, sella turcica and extension to cavernous sinus, dura mater and infratemporal fossa were evident on MRI and CT scan. The patient was treated only by palliative radiotherapy, but unfortunately, he died 3 months after the initial diagnosis.

Central odontogenic fibroma, hyperplastic dental follicle, or dentigerous cyst? A diagnostic dilemma: A case report.

Central odontogenic fibroma (COF) is an extremely rare benign odontogenic tumor, which is associated with an unerupted tooth in one-third of the cases. Hyperplastic dental follicle (HDF) is an odontogenic hamartomatous lesion associated with delayed or tooth eruption failure in young patients. Dentigerous cyst (DC) is an epithelial-lined developmental cyst surrounding the crown of an unerupted or impacted tooth. Here, we present a case of 13-year-old boy with pericoronal radiolucency around impacted right maxillary canine tooth, which detected during routine dental examination on panoramic radiograph. The size of radiolucency was varied between 5 and 10 mm and was asymmetrical. Lesion was underwent biopsy with suspicion to a dentigerous cyst. On microscopic examination, the lesion was composed of a cellular fibrous connective tissue with odontogenic epithelium in the form of strands or nests throughout the lesion and calcifications in the form of basophilic cementum-like material and dentinoid. Due to its nonspecific histological features, we encountered a diagnostic dilemma. In this case report, we discuss the clinical and radiologic features of COF, DC, and HDF. We preferred COF for this lesion. By combining surgical and orthodontic treatments, the impacted tooth was directed to its correct position in the maxilla. This case report highlights the importance of clinicopathological correlation in the diagnosis of pericoronal radiolucencies.

Primary intracranial peripheral primitive neuroectodermal tumor in an adult patient with aphasia: A rare case report.

Primary intracranial peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare malignancies that commonly affect children and adolescents. Only 10 cases over the age of 33 have been reported. pPNETs have an aggressive behavior and a high tendency for local recurrence and distant metastasis. Here, we present a case of supratentorial pPNET that affected the left frontoparietal lobe of a 36-year-old female patient. The patient complained of aphasia during the last 2 months. Aphasia is reported for the first time as a result of a pPNET. In T1-weighted MRI, a large mass with mixed isointense to hypointense signals was observed. The tumor was completely removed. Histopathologic examination was indicative of a small round cell tumor. Immunohistochemical analysis showed positivity for CD99. Presence of EWSR1 gene rearrangement confirmed the diagnosis. The patient's aphasia was gradually resolved post-surgery. Six months follow-up showed no evidence of local recurrence or metastasis.

Angiotensin-converting enzyme 1 and voltage-gated potassium channel-interacting protein 4 gene polymorphisms in COVID-19 patients from east of Iran.

BACKGROUND: Coronavirus disease 2019(COVID-19), the infectious respiratory disease caused by a newly discovered pathogen (severe acute respiratory syndrome coronavirus 2), is a pandemic that places a burden on the health care system. Recently, most research on COVID-19 has emphasized its profound impact on specific regions and ethnic groups. A possible explanation for these variations in disease presentation and severity might be differences in the gene pool of populations. This study therefore attempted to clarify possible involvements of genetic factors affecting COVID-19 pathogenesis with a focus on voltage-gated potassium channel-interacting protein 4 (KCNIP4) and angiotensin-converting enzyme 1 (ACE1) gene polymorphisms. MATERIALS AND METHODS: In this case-control study, the polymorphisms were genotyped using PCR in 194 COVID-19 patients and 194 healthy controls. RESULTS: COVID-19 susceptibility and severity appeared to be unaffected by these polymorphisms. However, this study supported the relevance of ACE1 II genotype frequency to a decreased number of deaths due to the infection. We found that COVID-19 patients with the ACE1 II genotype have a statistically significant better chance of survival (p = 0.008). CONCLUSION: This study strengthens the idea that the ACE1 I/D polymorphism can be a novel prognostic factor indicating the outcome of COVID-19.

Adrenocortical carcinoma in a patient with neurofibromatosis type 1: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF-1) is a genetic disorder. A heterogeneous group of benign and malignant neoplasms are associated with NF-1. Adrenocortical carcinoma (ACC) is an extremely rare invasive malignancy. The association of ACC with NF1 is not well understood. CASE PRESENTATION: We report a case of ACC in the context of NF1 in a 39- year-old woman who referred with the chief complaint of a mass in left abdomen. A left adrenal lesion was diagnosed by CT scan. Biochemical tests showed no abnormality. Adrenalectomy was done and histological and immunohistochemical findings confirmed ACC. Due to the absence of metastasis, clinical stage II was considered for the tumor. On follow-up after six months, she was still alive and well and with no evidence of metastasis. The age of patient and lack of secretion of adrenal cortical hormones in this case were unlike most ACCs. CONCLUSION: Also, modified Weiss score for malignancy of adrenocortical neoplasms, clinical staging system and different modality of treatment is discussed.

Comparison of Genotoxic Effect in Buccal Exfoliated Cells between Cigarette and Waterpipe Smokers.

BACKGROUND/AIM: Cytogenetic biomarkers such as micronuclei (MN) are used for the evaluation of exposure to carcinogens and genotoxic effects in oral epithelial cells. Tobacco is one of the strongest carcinogens responsible for the development of cancer in oral mucosa. The aim of this study was to compare the genotoxic effect of waterpipe smoking with that of cigarette smoking. METHODS: This case-control study was performed on 30 waterpipe smokers, 30 cigarette smokers, and 30 nonsmokers. Buccal exfoliated cells were prepared using cytobrushes and stained with the Papanicolaou technique. The cytologic slides were examined under a light microscope for counting the number of MN and the number of cells with MN per 1,000 epithelial cells. RESULTS: The mean number ± standard deviation (SD) of MN in waterpipe smokers, cigarette smokers, and nonsmokers was 7.55 ± 5.530, 4.95 ± 5.633, and 2.00 ± 2.406, respectively. The mean number ± SD of cells with MN in waterpipe smokers, cigarette smokers, and nonsmokers was 6.20 ± 4.830, 3.50 ± 3.832, and 1.45 ± 1.701, respectively. Numbers of cells with MN differed significantly between waterpipe smokers and cigarette smokers (p = 0.04) and between waterpipe smokers and nonsmokers (p < 0.001). Numbers of MN differed significantly between waterpipe smokers and nonsmokers (p < 0.001). Numbers of MN did not differ significantly between waterpipe smokers and cigarette smokers (p = 0.10). Numbers of MN and of cells with MN did not differ significantly between cigarette smokers and nonsmokers (p = 0.06 and p = 0.052, respectively). CONCLUSIONS: Waterpipe smoking is associated with a significantly higher frequency of MN, and it seems that waterpipe smoking has a greater genotoxic effect than cigarette smoking.

Assessment of oral cytological features in smokers and nonsmokers after application of toluidine blue.

INTRODUCTION: Smoking is the most important etiologic factor of oral cancer. Exfoliative cytology is the best method for early detection of oral cancer. Toluidine blue staining is used for detection of oral premalignant and malignant lesions. The aim of this study was to enhance the accuracy of oral exfoliative cytology in evaluating dysplastic features using toluidine blue staining. METHODS AND MATERIALS: This clinical trials study was performed on 60 male smokers and nonsmokers without clinically oral lesion. Oral exfoliative cytological smears were prepared before and after application of toluidine blue and stained with Papanicolaou and evaluated under light microscope. Cytological features such as cellular clumping nuclear-to-cytoplasmic ratio, cellular and nuclear pleomorphism, micronuclei, binucleation, presence of bacterial colonies, and keratin flakes were assessed and compared before and after application of toluidine blue. RESULTS: Results showed that cellular clumping and micronuclei were significantly decreased after application of toluidine blue and conversely cellular and nuclear pleomorphisms were significantly increased. Frequency of micronuclei and binucleation were greater in smokers than nonsmokers which were insignificant. Cellular and nuclear pleomorphisms were significantly higher in smokers than nonsmokers after application of toluidine blue. CONCLUSION: Toluidine blue improved cellular, nuclear, and structural features of oral cytological smears and filtered false-positive or false-negative results. Thus, application of toluidine blue in combination with oral exfoliative cytology for early detection of oral cancer is recommended. Diagn. Cytopathol. 2017;45:513-519. © 2017 Wiley Periodicals, Inc.

Two cases of clear cell ovarian cancer in young patients.

BACKGROUND: Ovarian cancer is the most common cause of cancer death worldwide. Incidence of ovarian cancer is more common in postmenopausal women. Premenopausal onset is rare and the present study described two cases of ovarian clear cell tumors in young women. CASE PRESENTATION: The patients presented with pelvic mass which was confirmed by sonography and laparotomy and final diagnosis was made according to histologic examination. Both patients showed a solid mass with cystic components in adnexal areas and explorative laparotomy demonstrated extension of tumors to abdomen in both patients. The level of CA 125 increased in both patients. For both tumors, immunohistochemical stainings were positive for CK7 and CD15, but CK20 was negative. CONCLUSION: Although ovarian clear cell tumor is usually diagnosed in postmenopausal women but its diagnosis should be suspected in young women with pelvic mass.

Comparison of Mast Cells Count in Odontogenic Cysts Using Histochemical Staining.

BACKGROUND & OBJECTIVES: Odontogenic cysts are among the most frequent destructive lesions of jaws which their pathogenesis and growth mechanism are not cleared. With respect to different roles of mast cells, they may play a role in the pathogenesis and growth of odontogenic cysts. The aim of present study was to evaluate mast cells in the most common odontogenic cyst. METHODS: Thirty paraffin-embedded tissue blocks including 10 radicular cysts, 10 dentigerous cysts and 10 odontogenic keratocysts were used and 5 micron sections stained with toluidine blue and observed by light microscope under ×400 magnification to evaluate mast cells within these cysts. For each case, 5 high-power field areas, selected from hot-spot areas, were considered and each area divided into 3 zones: intra-epithelial zone, sub-epithelial zone and deep zone. RESULTS: Most of the studied cyst showed presence of mast cells. There was not any significant difference in mast cell count between studied cysts ( P -values > 0.05).With respect to intra-epithelial, sub-epithelial and deep zones, there was not any significant difference between three studied cysts. There was not any significant difference between sub-epithelial zone and deep zone within each of these cysts. There was only significant difference between intra-epithelial zone and sub-epithelial zone within dentigerous cysts and odontogenic keratocysts ( P -value < 0.05). CONCLUSIONS: Prevalence of mast cells in fibrous wall of odontogenic cysts suggests their activity in these cysts. Mast cells may not be directly involved in the pathogenesis of odontogenic keratocysts.

Metastatic Renal cell Carcinoma Presenting as a clear-cell Tumor in Tongue: A Case Report.

INTRODUCTION: Metastatic lesions of the oral cavity are extremely rare, accounting for approximately 1% of all malignant oral tumors. The most common primary sources of metastatic tumors in the oral region are, from the most to the least common, the breast, lung, kidney, bone, and colon. Renal cell carcinoma accounts for nearly 3% of all adult malignancies. It usually metastasizes to the lungs, bone, adrenal glands, and regional lymph nodes. The incidence of metastasis from renal cell carcinoma to the head and neck region is very low. The tongue is considered a very rare atypical ear, nose, and throat (ENT) location for metastasis of renal cell carcinoma. The present case from Iran reports tongue metastasis of renal cell carcinoma (RCC). CASE REPORT: The following report is based on an 80-year old male patient with a tongue lesion and ambiguous past medical history that ultimately leads to diagnosis of a metastatic RCC. We also updated a previous literature review that was published 2008. A histopathological differential diagnosis for clear-cell tumors is also discussed. CONCLUSION: Because of the rarity of metastatic tumors of the oral region as well as the presence of other lesions with clear cells, diagnosis of metastatic clear-cell RCC in the oral cavity can be very difficult and challenging.