Background: Head and neck cancer is included among the top five most commonly prevailing cancers worldwide. Abnormalities of either genetic or epigenetic factors are found responsible for the development and progression of head and neck cancer. Metastasis is the leading cause of death in patients with head and neck cancer. Down regulation of metastasis suppressor genes (MSGs) expression have been frequently observed in advanced tumours. Methodology: The present study was designed to screen two of the most frequently down-regulated MSGs (KISS1and KAI1) for mutations in 120 diagnosed head and neck cancer affected Pakistani patients. The questionnaire was filled for basic information about age, gender, smoking habits and area of cancer affected and other relevant details. Primers for both genes were designed using “Primer 3” software in such a way that both intron exon boundaries were included in this region. DNA isolation and estimation was done by using organic method and agarose gel electrophoresis. Single Strand conformational polymorphism technique was used after amplification of the respective genes. Mobility patterns were analyzed using BioDoc Analyzer.
Results: Data of patients were analyzed on the basis of age, sex and type of cancer as variables. The mean age of patients and controls was 44 years. There were 53% females and 47% males in this group of study, 63% nonsmokers and 37% smokers and larynx cancer was found to be most frequent type of cancer with a percentage of 64. Lack of germ line mutation was observed in the entire coding region in both coding regions as well as splice sites of the respective genes.
Conclusion: Germ line mutations in KISS1 and KAI1 are thus considered to be a less frequent event in head and neck cancer patients. However, two polymorphisms in intronic region of exon 3 and exon 9 of KAI1 gene were observed in 1% of patients. In non coding region downstream of exon 3 (KAI1), there was a C 29166 T substitution and in intronic region upstream exon 9 of KAI1 gene, a C 52840 A substitution was observed. Both patients were females with ages 47 and 50 years respectively. A detailed analysis of regulatory mechanism is required to explore the genetic basis of down regulation of these MSGs for a better understanding of head and neck cancer progression.