Clinical and genealogical studies of familial colorectal cancer type-x in Newfoundland

Harnett, David (2011) Clinical and genealogical studies of familial colorectal cancer type-x in Newfoundland. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (16MB)

Abstract

Familial Colorectal Cancer Type-X (FCCTX) is a syndrome defined by criteria used to identify Lynch Syndrome, but in which the genetic cause is not the result of mismatch repair (MMR) gene mutations with the genetic etiology remaining unknown. In an attempt to facilitate novel gene discovery in FCCTX, families (N = 12) were identified with a strong family history of CRC (≥5 cases of CRC) of unknown genetic etiology, who fulfilled the criteria for FCCTX: meeting the ACI, possessing no known MMR gene mutation, and a probands with MSS CRC. Significant variability was found in terms of age of onset, tumour location, and genetic profile of CRCs amongst the probands of these families. First-degree relatives of the probands of the FCCTX families (N = 126) were compared as a group to first-degree relatives of the probands of fifteen Lynch Syndrome families (N = 153). No difference in lifetime risk of CRC existed between the groups, but the families fulfilling the FCCTX criteria demonstrated a significantly later onset of CRC and fewer cases of extra-colonic cancers. Mapping locations of origin demonstrated that families originated from multiple different geographic isolates. The use of a customized hereditability database failed to demonstrate genealogical linkages between the twelve FCCTX families. In six of the FCCTX families, further archival research also failed to yield a direct link. The heterogeneous clinical and pathological features, geographic distribution of probands in different isolates, and failure to identify genealogical linkages between families suggest that multiple genes underlie the susceptibility to CRC observed in FCCTX.

Actions (login required)

View Item