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A Case-Control Study of ATM and Susceptibility to Squamous Cell Carcinoma of the Head and Neck

Grams, Sarah Elizabeth (2007) A Case-Control Study of ATM and Susceptibility to Squamous Cell Carcinoma of the Head and Neck. Master's Thesis, University of Pittsburgh. (Unpublished)

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The American Cancer Society estimates that >500,000 new cases of squamous cell carcinomas of the head and neck (SCCHN) are diagnosed each year. Although the incidence varies widely around the world, it is especially high in developing countries and is positively associated with higher rates of exogenous risk factors including, smoking, alcohol use, and viral infection. But, only a fraction of the people in these high-risk groups will develop the disease. Treatment times tend to be long and costly with survival rates averaging 50%, one of the lowest for the major cancers. Therefore, further work is needed to aid in our understanding of genetic and environmental risk factors, as well as the underlying biology of SCCHN. To further assess the etiology of SCCHN, the study used the approach of examining one candidate gene, the Ataxia Telangiectasia Mutated gene (ATM), located at 11q22.3 and functioning in the DNA damage response/repair pathway. Compared to other cancers, SCCHN tumors exhibit a very high rate of chromosomal instability, often showing amplification of chromosome 11q13 and loss of 11q22-qter. We hypothesized that SCCHN patients (cases) have a higher incidence of germline alterations in ATM than controls. Three hundred cases and 360 controls were genotyped for nine ATM tag-SNPs and supplemented with one splice-site SNP. Logistic regression analysis showed that two SNPs (rs611646 and rs373759) were associated with increased risk of developing SCCHN: P = 0.012 and P = 0.025, respectively. In SNP rs611646, the TT genotype was more common in cases than controls (45 versus 32%) while the AA and AT genotypes were less common in cases than controls (18 versus 21% and 37 versus 46%, respectively). In SNP rs373759, the CC genotype was more common in cases than controls (56 versus 48%) with the CT type being less common in cases than controls (29 versus 40%). Genetic studies such as this could have a public health impact by identifying markers for early detection of SCCHN, for predicting prognosis, for therapy and drug development, and aiding in the development of new, individualized treatment strategies.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Grams, Sarah
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGollin, SusanneSusanne.Gollin@hgen.pitt.eduGOLLIN
Committee MemberFeingold, EleanorEleanor.Feingold@hgen.pitt.eduFEINGOLD
Committee MemberTaioli,
Committee MemberFerrell, Robertrobert.ferrell@hgen.pitt.eduRFERRELL
Date: 25 September 2007
Date Type: Completion
Defense Date: 1 June 2007
Approval Date: 25 September 2007
Submission Date: 13 June 2007
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Cancer biology; Cell cycle checkpoints; DNA damage; DNA repair; Double strand breaks; Genomic instability; Haplotype; Hapmap; Hereditary cancer syndromes; HNSCC; HPV; Laryngeal cancer; Linkage disequilibrium; Oral cancer; Pharyngeal cancer; Single nucleotide polymorphism; SNP association; Taqman; Tumor studies
Other ID:, etd-06132007-092438
Date Deposited: 10 Nov 2011 19:47
Last Modified: 15 Nov 2016 13:44


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