Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer.

Abstract	A common polymorphism in the cyclin D1 gene enhances the gene's alternate splicing. The alternatively spliced product encodes an altered protein that does not contain sequences involved in the turnover of the protein. We found that hereditary nonpolyposis colorectal carcinoma patients who were homozygous or heterozygous for the mutant allele developed colorectal cancer an average of 11 years earlier than patients who were homozygous for the normal alleles. This is the first report indicating that the cyclin D1 polymorphism influences age of onset of cancer. Because cyclin D1 plays an important role in the G1 to S phase transition of the cell cycle, our findings suggest that cells with the mutant allele accumulate mutations as a result of defective mismatch repair and may also bypass the G1-S checkpoint of the cell cycle more easily than in cells not carrying the polymorphism. The polymorphism has a dominant phenotype.
Authors	S Kong, C I Amos, R Luthra, P M Lynch, B Levin, M L Frazier
Journal	Cancer research (Cancer Res) Vol. 60 Issue 2 Pg. 249-52 (Jan 15 2000) ISSN: 0008-5472 [Print] United States
PMID	10667569 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Adaptor Proteins, Signal Transducing Carrier Proteins DNA-Binding Proteins Fungal Proteins MLH1 protein, human Neoplasm Proteins Nuclear Proteins PMS1 protein, human Proto-Oncogene Proteins Cyclin D1 MSH2 protein, human MutL Protein Homolog 1 MutL Proteins MutS Homolog 2 Protein
Topics	Adaptor Proteins, Signal Transducing Adult Age of Onset Aged Aged, 80 and over Base Pair Mismatch Base Sequence Carrier Proteins Cell Cycle Colorectal Neoplasms, Hereditary Nonpolyposis (genetics, mortality, pathology, physiopathology) Cyclin D1 (genetics) DNA-Binding Proteins Ethnicity Female Fungal Proteins (genetics) Genetic Carrier Screening Homozygote Humans Male Middle Aged MutL Protein Homolog 1 MutL Proteins MutS Homolog 2 Protein Mutation, Missense Neoplasm Proteins (genetics) Nuclear Proteins Polymorphism, Genetic Proto-Oncogene Proteins (genetics) Survival Analysis

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!