Clarke, Erica L. (2012) Involvement of Galnt12 variants in inherited susceptibility to colorectal cancer. Masters thesis, Memorial University of Newfoundland.
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Colorectal cancer (CRC) is a major health concern in the Canadian province of Newfoundland and Labrador (NL), as this population has the second highest incidence of CRC in North America. Previous mutation analysis in the NL CRC population has revealed that the high frequency of hereditary CRC in NL is likely attributable to novel susceptibility genes. A recent study suggests that N-acetylgalactosaminyltransferase 12 ( GALNT12 ) may be a novel gene associated with CRC susceptibility. The purpose of this study was to investigate the impact ofGALNT12 germline variants in CRC families from NL and in 481 cases from the Newfoundland Colorectal Cancer Registry (NFCCR) with an unknown molecular basis for their disease. -- GALNT12 was first sequenced in 129 CRC families to investigate if variants within this gene segregate with the disease. Probands included in the study have a high family incidence of CRC and were referred to the Provincial Medical Genetics Program. DNA from 481 patients from the NFCCR was also sequenced in exons 4 and 6 to identify causal variants. -- Two putatively pathogenic variants were identified in the GALNT1 2 gene within four clinical family probands - c.907G>A, p.Asp303Asn (three probands), and c.1187A>G, p.Tyr396Cys. Two families showed partial segregation of c.907G>A with CRC or adenomas. The c.907G>A variant was identified in an additional two cases after sequencing 481 cases from the NFCCR. Another variant, c.889C>T, was also identified that was previously reported in a CRC case. This study provides some support for the association between GALNTI2 and CRC susceptibility and suggests that further investigations should be performed.
|Item Type:||Thesis (Masters)|
|Additional Information:||Includes bibliographical references (leaves 88-97).|
|Department(s):||Medicine, Faculty of|
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