Identification of Squamous Cell Carcinoma Susceptibility Genes Using Homozygous Mapping
Advisor:Toland, Amanda E.
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. College of Biological Sciences Honors Theses; 2010
The Ohio State University. Department of Psychology Honors Theses; 2010
Cutaneous squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. SCC is the second most common skin tumor with a lifetime risk of 7-11 percent. It is a neoplasm of epidermal keratinocytes characterized by loss of cellular structure and architecture. The molecular pathways leading to the development of SCC remain poorly defined. Loss of heterozygosity (LOH) in tumors is a frequent event contributing to tumorigenesis. Homozygous loci have two identical alleles or DNA sequences, and a higher frequency of genomic homozygosity has been observed in normal DNA from cancer patients compared to controls. Thus, there may be an increased likelihood that stretches of consecutive homozygous markers, or runs of homozygosity (ROH), may occur at loci containing cancer susceptibility genes. Based on these observations, our first hypothesis is that ROH are more frequent in normal DNA from individuals with SCC. Secondly, we hypothesize that certain single nucleotide polymorphisms (SNPs) are associated with risk of SCC. To test these hypotheses, DNA from SCC patients and controls were genotyped at 123 SNPs mapping to Chromosomes 7 and 11 by Sequenom Mass ARRAY. We observed similar frequencies of homozygosity in cancer and non-cancer patients and no significant ROH were identified. One SNP on chromosome 7 and two SNPs on chromosome 11 had significant odds ratios (OR) for SCC risk in the homozygous state. Three SNPs mapping to Hdac9 on chromosome 7 and five SNPs mapping to DRD2 and KIRREL3 on chromosome 11 show protective effects. From these data, we conclude that some SNPs on chromosome 7 and 11 may increase the risk of developing SCC and others promote protection. We found Hdac9, DRD2, and KIRREL3 to be potential candidate genes that affect SCC susceptibility. Additional studies are needed to confirm these results and identify skin cancer susceptibility and resistance genes.