Inherited susceptibility to colorectal adenomas and carcinomas: evidence for a new predisposition gene on 15q14-q22.

Abstract:

BACKGROUND & AIMS:The aim of this study was to evaluate the role of known colorectal adenoma and carcinoma susceptibility genes and to locate a novel susceptibility gene in an Ashkenazi family (SM1311) with dominantly inherited predisposition to colorectal adenomas and carcinomas. METHODS:Clinicopathologic and family history data were collected. Genetic linkage and mutational analyses were used to investigate the genetic basis of the family's disease. RESULTS:Affected members of SM1311 develop multiple tubular, villous, tubulovillous, and/or serrated colorectal adenomas throughout the large bowel, and some develop colon carcinoma. There are no extracolonic features clearly associated with disease in SM1311. We have shown that the family's phenotype does not result from APC mutations (including the I1307K variant) or from genetic changes in the other known genes that predispose to colon cancer. Using genetic linkage analysis, supplemented by allele loss in tumors, we have provided evidence for a new colorectal cancer susceptibility gene, CRAC1 (colorectal adenoma and carcinoma), mapping to chromosome 15q14-q22. CONCLUSIONS:We provide evidence for a novel colorectal adenoma and carcinoma susceptibility gene on chromosome 15q14-q22. Further studies are needed to confirm this localization and to evaluate the contribution of CRAC1 to this disease.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Tomlinson I,Rahman N,Frayling I,Mangion J,Barfoot R,Hamoudi R,Seal S,Northover J,Thomas HJ,Neale K,Hodgson S,Talbot I,Houlston R,Stratton MR

doi

10.1016/s0016-5085(99)70061-2

keywords:

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

789-95

issue

4

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(99)70061-2

journal_volume

116

pub_type

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