Background/Aim: The study aimed to evaluate associations of relative leukocyte telomere length (LTL) and polymorphisms of telomere length-associated genes TERT (rs2736098), TERT-CLPTM1L (rs401681), TRF1 (rs1545827, rs10107605) and TNKS2 (rs10509637, rs10509639) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and Methods: The study consisted of 300 patients with LSCC and 369 healthy control subjects. Genotyping and relative LTL measuring were carried out using qPCR. Results: Relative LTL was statistically significantly shorter in the G3 (tumor differentiation grade) subgroup of patients with LSCC compared to the G1 and G2 subgroups. Significant differences were found in genotype distributions of TERT rs401681 and TNKS2 rs10509639 between the study groups. TERT rs401681 C/T and T/T genotypes were associated with approximately 30% decreased odds of LSCC development. Conclusion: LTL was shorter in the G3 subgroup compared to the G2 and G1 subgroups of LSCC patients. TERT rs401681 and its C/T and T/T genotypes were associated with decreased odds of overall LSCC development. Laryngeal squamous cell carcinoma (LSCC) represents one of the most common upper respiratory tract tumors and ranks 20th among all oncological diseases in Europe (1). According to published data, LSCC accounts for 2.4% of all 431 This article is freely accessible online.
Background/Aim: The matrix metalloproteinases (MMP) play an important role in the physiological and pathological remodeling of tissues including carcinogenesis. The study's aim was to assess the relations between MMP-2(-735C/T), MMP-2(-1306C/T), MMP-9(-1562C/T), and MMP-3(-11715A/6A) polymorphisms, and clinical/morphological manifestation of laryngeal squamous cell carcinoma (LSCC) and benign vocal fold lesions (BVFL). Patients and Methods: Two hundred and seventeen patients with LSCC and BVFL and 458 controls were included in this study. The genotyping was performed using the real-time polymerase chain reaction method. Results: The MMP-2(-1306C/T) C/T genotype was significantly rarer among the patients with moderate-poorly differentiated LSCC compared to the control group, however the MMP-3(-11715A/6A) 6A/6A genotype was significantly more frequent compared to controls. Smoking and 6A/6A genotype of MMP-3(-11715A/6A) polymorphism were associated with increased odds of LSCC risk. No associations between MMP genotypes and BVFL were found. Conclusion: Smoking and MMP-3 (-11715A/6A) 6A/6A genotype may cause a higher risk for developing LSCC. Head and neck squamous cell carcinoma (HNSCC), which includes tumors of the oral cavity, pharynx, hypopharynx, and larynx is one of the most common cancers worldwide (1). Laryngeal squamous cell carcinoma (LSCC) constitutes approximately 2-3% of all malignant tumors representing the most common neoplasm of the head and neck region. According to the morbidity rate, LSCC ranks second among the neoplasms of the respiratory system after lung cancer (2). Despite the current advances in diagnostics, surgery, radiotherapy and chemotherapy, there was no significant increase in the 5-year survival rate in the last few decades (3). Following LSCC treatment, the quality of life of patients in advanced stages of the disease often remains significantly impaired, manifesting with dysphagia and loss of voice and speech (4). The laryngeal carcinoma does not occur in unaltered tissues. It is formed under the influence of harmful habits when hyperplastic (dysplasia, atypia) changes emerge in squamous cell epithelium. Many factors, such as smoking, alcohol use, HPV infection, and genetic predisposition are associated with an increased risk of LSCC (5). Although tobacco and alcohol addiction play a critical role in LSCC carcinogenesis, only a small proportion of smokers and drinkers are finally diagnosed with LSCC. This leads to presuming that genetic susceptibility to LSCC may vary in the general population (6). The important role of matrix metalloproteinases (MMPs) in HNSCC development has been established in the last decades (7). MMPs belong to a family of zinc-containing enzymes which are responsible for degrading all extracellular matrix components, which is a very important event during the cancer cell invasion process and metastasis of most neoplasms (8). MMPs represent the endopeptidases that contain an active site Zn 2+ and are divided into subfamilies based on relationships and structure ...
BACKGROUND: SIRT1 is a multifunctional protein, possibly essential in tumorigenesis pathways, which can act both as a tumor promoter and tumor suppressor depending on the oncogenes, specific to particular tumors. Pathogenesis of laryngeal cancer is multifactorial and the association of SIRT1 expression with the clinical characteristics and prognosis of LSCC has not been fully identified. OBJECTIVES: The study aimed to evaluate associations between single gene nucleotide polymorphisms (SNPs) of SIRT1 (rs3818292, rs3758391, and rs7895833), serum SIRT1 levels, and 5-year survival rate in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: The study involved 302 patients with LSCC and 409 healthy control subjects. The genotyping of SNPs was performed using RT-PCR, and serum SIRT1 levels were determined by the ELISA method. RESULTS: Our study found significant differences in genotype distributions of SIRT1 rs3758391 polymorphisms between the study groups. SIRT1 rs3758391 T/T genotype was associated with the increased LSCC development odds (OR = 1.960 95% CI = 1.028–3.737; p= 0.041). Carriers of SIRT1 rs3758391 T/T genotype had statistically significantly increased odds of LSCC development into advanced stages under the codominant and recessive genetic models (OR = 2.387 95% CI = 1.091–5.222; p= 0.029 and OR = 2.287 95% CI = 1.070–4.888; p= 0.033, respectively). There were no statistically significant differences in serum SIRT1 levels between the LSCC and control groups. However, LSCC patients with SIRT1 rs3818292 AG genotype demonstrated a tendency to significantly lower SIRT1 serum levels than controls (p= 0.034). No statistically significant associations between SIRT1 (rs3818292, rs3758391, and rs7895833) SNPs and the 5-year survival rate of LSCC patients were found. CONCLUSION: The present study indicated a statistically significant association between the SIRT1 rs3758391 T/T genotype and increased LSCC development odds. LSCC patients with SIRT1 rs3818292 AG genotype showed a tendency to manifest with lower SIRT1 serum levels. No associations between SIRT1 SNPs and the 5-year survival rate of LSCC patients were detected.
Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients’ five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development.
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