Collaboration of major biomedical centers has shown convergence on a cellular process for head and neck cancers

Source: www.rxpgnews.com Author: Broad Institute of MIT and Harvard Powerful new technologies that zoom in on the connections between human genes and diseases have illuminated the landscape of cancer, singling out changes in tumor DNA that drive the development of certain types of malignancies such as melanoma or ovarian cancer. Now several major biomedical centers have collaborated to shine a light on head and neck squamous cell cancer. Their large-scale analysis has revealed a surprising new set of mutations involved in this understudied disease. In back-to-back papers published online July 28 in Science, researchers from the Broad Institute, Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and the University of Texas MD Anderson Cancer Center have confirmed genetic abnormalities previously suspected in head and neck cancer, including defects in the tumor suppressor gene known as p53. But the two teams also found mutations in the NOTCH family of genes, suggesting their role as regulators of an important stage in cell development may be impaired. "This adds a new dimension to head and neck cancer biology that was not on anyone's radar screen before," said Levi A. Garraway, a senior associate member of the Broad Institute, an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, and a senior author of one of the Science papers. "Head and neck cancer is complex and there are many mutations, but we can infer there is a convergence on a cellular process for which we previously did not have [...]

A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

Source: 7thspace.com Author: Paola Galli et al. The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population. Methods: Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms. Results: We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08-4.56), and a protective effect for those carrying the p53 exon 4- p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47-0.92). From the gene-environment interaction analysis we found that individuals aged <45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10-78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23-1.16). Conclusion: Our study provides for [...]

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