The role of genetic susceptibility in head and neck squamous cell carcinoma

Abstract

Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).

Loss of Heterozygosity at the 9p21–24 Region and Identification of BRM as a Candidate Tumor Suppressor Gene in Head and Neck Squamous Cell Carcinoma

“…Our analysis revealed a loss rate of 46% at the marker D9S1748 mapped at 9p21. In line with our findings, a similar loss rate in HNSCC was also reported by Kamal-Eldin et al (4). 16INK4A (also referred to as p16) is an important tumor suppressor candidate mapped at 9p21.…”

“…Also treatment with this inhibitor causes suppression of tumor growth in the FaDu xenograft mice (15). Although LOH of the 9p chromosomal region has been reported previously in HNSCC (4)(5)(6), in this study we have expanded our region of analysis until the subtelomeric area by incorporating three microsatellite markers (GATA62F03, D9S199, and D9S1813) located in 9p24; these markers are close to the BRM gene locus. This analysis revealed a relatively high rate of LOH at all markers, and especially at the GATA62F03 marker (53.6%).…”

“…Previous studies have also investigated LOH of 9p in head and neck tumors (4)(5)(6). However, most of these studies were genomewide studies and used limited number of microsatellite markers, which are widely separated.…”

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

“…In addition, miR-204 is located at the cancer-associated genomic region 9q21.1-q22.3 locus in human head and neck cancer [16][17][18].…”

DNA Repair Capacity and the Risk of Head and Neck Cancer

“…Hence, it was deduced that a combination of exogenous exposure and individual predisposition is responsible for carcinogenic transformation (Taioli, 2008 to cancer risk and connected with cancer progression was written by Vogelstein and Kinzler (2004). An impact of genetic factor on health effects of tobacco smoking was also discussed more specifically in relation to head and neck cancer (Badawy et al, 2008;Rossing, 1998). As such specific genes as BRCA1 or APC involved in breast and colon cancer, respectively, were not discovered in head and neck cancer, an attention was paid on so-called "lowpenetration" genes, mainly those involved in carcinogens processing.…”