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http://purl.uniprot.org/citations/19690970http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19690970http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Lynch syndrome is an autosomal dominant syndrome of familial malignancies resulting from germ line mutations in DNA mismatch repair (MMR) genes. Our goal was to take a pathway-based approach to investigate the influence of polymorphisms in cell cycle-related genes on age of onset for Lynch syndrome using a tree model.

Experimental design

We evaluated polymorphisms in a panel of cell cycle-related genes (AURKA, CDKN2A, TP53, E2F2, CCND1, TP73, MDM2, IGF1, and CDKN2B) in 220 MMR gene mutation carriers from 129 families. We applied a novel statistical approach, tree modeling (Classification and Regression Tree), to the analysis of data on patients with Lynch syndrome to identify individuals with a higher probability of developing colorectal cancer at an early age and explore the gene-gene interactions between polymorphisms in cell cycle genes.

Results

We found that the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 variant genotype, AURKA wild-type genotype, and CCND1 variant genotype had the youngest age of onset, with a 45-year median onset age, while the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 wild-type genotype, and AURKA variant genotype had the latest median age of onset, which was 70 years. Furthermore, we found evidence of a possible gene-gene interaction between E2F2 and AURKA genes related to CRC age of onset.

Conclusions

Polymorphisms in these cell cycle-related genes work together to modify the age at the onset of CRC in patients with Lynch syndrome. These studies provide an important part of the foundation for development of a model for stratifying age of onset risk among those with Lynch syndrome."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.org/dc/terms/identifier"doi:10.1007/s10552-009-9416-x"xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Zhang Q."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Amos C.I."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Lindor N.M."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Frazier M.L."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Lynch P.M."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Etzel C.J."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/author"Viscofsky N."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/name"Cancer Causes Control"xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/pages"1769-1777"xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/title"Genetic variants in the cell cycle control pathways contribute to early onset colorectal cancer in Lynch syndrome."xsd:string
http://purl.uniprot.org/citations/19690970http://purl.uniprot.org/core/volume"20"xsd:string
http://purl.uniprot.org/citations/19690970http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19690970
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