Prevalence of the TGFBR1 tumor susceptibility allele in young patients with oral squamous cell carcinoma Free

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INTRODUCTION: Recent studies have revealed a steady increase in the incidence of oral squamous cell carcinoma (OSCC) in patients 40 years of age or younger. Many of these patients lack traditional risk factors for OSCC, such as tobacco and alcohol use, indicating the possibility of underlying genetic factors influencing the development of cancer in this population. TGFBR1*6A is a common polymorphism of the type I TGF-beta receptor (TGFBR1), which tranduces TGF-beta growth inhibitory signals less effectively than TGFBR1. The *6A allele consists of a deletion of 3 alanines within a 9-alanine (*9A) repeat at the 3’-end of the exon 1 coding sequence, and epidemiological studies suggest it may act as a tumor susceptibility allele. Our previous work in head and neck squamous cell carcinoma (HNSCC) revealed 21.7% (49/226) of patients possessed the *6A allele compared to healthy control individuals (13.7%; 473/3451). Other non-9A alleles (*5A, *8A, *14A) were also identified in 3 additional cases (23%; 52/226). The purpose of the current study was to examine the frequency of the TGFBR1*6A tumor susceptibility allele in young OSCC patients.
 >METHODS: Genomic DNA was extracted from tumor specimens obtained from OSCC patients 40 years of age or younger, according to protocols approved by the IRB of The Ohio State University (OSU). TGFBR1 exon 1 was amplified using PCR, and the PCR products genotyped by OSU Plant Microbe Genomics Facility (OSU PMGF) using a 3730 DNA Analyzer (Applied Biosystems).
 >RESULTS: A total of 16 oral tumors were genotyped, with 5 (31.3%) possessing non-9A hypomorphic allele variants. Three patients had a genotype of *6A/*9A (18.8%), one patient had a genotype of *5A/*9A (6%), and one patient had a genotype of *9A/*10A (6%). There was a statistically significant difference in the proportion of non-*6A hypomorphic alleles present in the young OSCC group (12.5%) as compared to the HNSCC (1.33%) group (P-value = 0.0365).
 >CONCLUSIONS: Preliminary results from this small cohort of young OSCC patients indicate that a hypomorphic TGFBR1 allele may be influencing tumor susceptibility in this population. Further study of a larger cohort is needed to better characterize the proportion of hypomorphic TGFBR1 alleles in OSCC patients 40 years of age or younger and define the role of this susceptibility allele in HNSCC tumorigenesis.
 >SUPPORT: NIH/NIDCR T32DE014320, NCI P01DE12704 and R01DE011943, The V Foundation
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