Dataset Information

Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck.

ABSTRACT: The Pentose Phosphate Pathway (PPP) is involved in the body's protection against oxidative stress and resistance/susceptibility to apoptosis and thus has been implicated in tumor development and progression. Here we present data examining the association of genetic variation in one of the key enzymes of the PPP, Transaldolase 1 (TALDO1) with squamous cell carcinoma of the head and neck (SCCHN).We performed sequencing analysis to identify common genetic variations in TALDO1 and then investigated their association with SCCHN using samples from a population-based case/control study with both European American (EA) and African American (AA) former and current smokers.We identified three polymorphisms in TALDO1 that were associated with SCCHN risk in our EA study population. Specifically the 5' upstream variant -490C>G or T (rs10794338), which we identified as tri-allelic, showed a reduced risk compared with any presence of the common allele, odds ratio (OR) [95% confidence interval (95% CI)]: 0.57 (0.38-0.86). Additionally two intronic high frequency polymorphisms demonstrated a positive association with disease, with the presence of the variant IVS1+1874T>A (rs3901233), 1.76 (1.19-2.61) and IVS4+2187A>C (rs4963163), 1.71 (1.16-2.53).These results provide preliminary evidence that genetic polymorphisms in TALDO1 are associated with SCCHN.

SUBMITTER: Basta PV

PROVIDER: S-EPMC2614275 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck.

Basta Patricia V PV Bensen Jeannette T JT Tse Chiu-Kit CK Perou Charles M CM Sullivan Patrick F PF Olshan Andrew F AF

Cancer detection and prevention 20080920 3

<h4>Background</h4>The Pentose Phosphate Pathway (PPP) is involved in the body's protection against oxidative stress and resistance/susceptibility to apoptosis and thus has been implicated in tumor development and progression. Here we present data examining the association of genetic variation in one of the key enzymes of the PPP, Transaldolase 1 (TALDO1) with squamous cell carcinoma of the head and neck (SCCHN).<h4>Methods</h4>We performed sequencing analysis to identify common genetic variatio ...[more]

PMID: 18805652

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Project description:BackgroundRecurrence and/or metastasis occurs in more than half of patients with head and neck squamous cell carcinoma (HNSCC), and these events pose the greatest threats to long-term survival. We set out to identify genetic alterations that underlie recurrent/metastatic HNSCC.MethodsWhole-exome sequencing (WES) was performed on genomic DNA extracted from fresh-frozen whole blood and patient-matched tumor pairs from 13 HNSCC patients with synchronous lymph node metastases and 10 patients with metachronous recurrent tumors. Mutational concordance within and between tumor pairs was used to analyze the spatiotemporal evolution of HNSCC in individual patients and to identify potential therapeutic targets for functional evaluation.ResultsApproximately 86% and 60% of single somatic nucleotide variants (SSNVs) identified in synchronous nodal metastases and metachronous recurrent tumors, respectively, were transmitted from the primary index tumor. Genes that were mutated in more than one metastatic or recurrent tumor, but not in the respective primary tumors, include C17orf104, inositol 1,4,5-trisphosphate receptor, type 3 (ITPR3), and discoidin domain receptor tyrosine kinase 2 (DDR2). Select DDR2 mutations have been shown to confer enhanced sensitivity to SRC-family kinase (SFK) inhibitors in other malignancies. Similarly, HNSCC cell lines harboring endogenous and engineered DDR2 mutations were more sensitive to the SFK inhibitor dasatinib than those with WT DDR2.ConclusionIn this WES study of patient-matched tumor pairs in HNSCC, we found synchronous lymph node metastases to be genetically more similar to their paired index primary tumors than metachronous recurrent tumors. This study outlines a compendium of somatic mutations in primary, metastatic, and/or recurrent HNSCC cancers, with potential implications for precision medicine approaches.FundingNational Cancer Institute, American Cancer Society, Agency for Science, Technology and Research of Singapore, and Gilead Sciences Inc.

Dataset Information

Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck.

Publications

Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck.

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