The investigation of single nucleotide polymorphisms in genes of the cell cycle and related pathways as candidate modifiers of the age of disease onset in hereditary nonpolyposis colorectal cancer

Adams, Aimée Dawn (2009) The investigation of single nucleotide polymorphisms in genes of the cell cycle and related pathways as candidate modifiers of the age of disease onset in hereditary nonpolyposis colorectal cancer. Masters thesis, Memorial University of Newfoundland.

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Abstract

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is the most common type of inherited colorectal cancer. Eighty to ninety percent of identified mutations in HNPCC families involve MSH2 or MLH1 genes. However, a great degree of variability has been observed within and between families carrying the same mutation. Therefore, other factors such as modifying genes may be involved in the presentation of this disease. The cell cycle, the mismatch repair pathway, and folate metabolism have been associated with cancer. Therefore, I studied 31 single nucleotide polymorphisms (SNPs) from genes in these pathways to determine if they had a modifying effect on the disease penetrance. Two MSH2 kindreds were used in this study, one from Newfoundland and one from the Lower North Shore of Quebec. They included 135 mutation carriers. I identified 3 SNPs CCND1¹⁷²²GC, CCNA2 GA, and CDKN1B ( p27KIP1 ) TG, which had significant effect on the age of disease onset.

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