Matrix Metalloproteinases (MMP-2,-3,-9) Gene Polymorphisms in Cases of Benign Vocal Fold Lesions and Laryngeal Carcinoma

Abstract

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 ...

Matrix metalloproteinase gene mutations and bioinformatics of telocytes in hepatocellular carcinoma

“…After verification in tumor tissues by IHC and western blot assays, we confirmed that MMP1, MMP9, and MMP17 expression in HCC and CC was increased. These results suggest that gene mutations in TCs might play a pivotal role in the HCC, which has been coincidently reported that MMP9 C/T mutation increases MMP9 overexpression and accelerates the progression of papillary thyroid carcinoma as well as head and neck squamous cell carcinoma (W. Li et al, 2019; Liutkevicius et al, 2020; Roncevic et al, 2019). Furthermore, it was indispensable to predict correlative criticality of SNPs mutations in MMP1, MMP9, and MMP17 through the Polyphen‐2 database, and then, we found that allele shifts of C/T (rs20544) and G/C (rs2250889) in MMP9 were risk factors in HCC.…”

“…Subsequently, we found expression in HCC and CC was increased. These results suggest that gene mutations in TCs might play a pivotal role in the HCC, which has been coincidently reported that MMP9 C/T mutation increases MMP9 overexpression and accelerates the progression of papillary thyroid carcinoma as well as head and neck squamous cell carcinoma (W. Li et al, 2019;Liutkevicius et al, 2020;Roncevic et al, 2019). (Nagar et al, 2002).…”

Association Between MMP8 Gene Polymorphisms and Laryngeal Squamous Cell Carcinoma

“…of a recent study revealed that combination of smoking and 6A/6A genotype of MMP3 (-1171 5A/6A) polymorphism are associated with significantly increased odds of LSCC, thus confirming a presumably important role of MMP3 (-1171) 6A/6A genotype in LSCC carcinogenesis (21).…”

Wild‑type KRAS inhibits the migration and invasion of pancreatic cancer through the Wnt/β‑catenin pathway

“…A previous study demonstrated that MMP-9 is highly expressed in non-small cell lung, cervical and ovarian cancer, among others, and has become one of the important factors related to cancer metastasis and invasion ( 28 ). MMP-3 protein breaks down a variety of extracellular matrix molecules and cleaves various adhesion molecules, growth factors and other MMPs ( 29 ). MMP-3 can activate MMP-1 and other family members and its overexpression is associated with the growth and metastasis of various cancers, including breast cancer ( 30 ).…”