Risk and surveillance of individuals with heritable factors for XXXX . WHO Collaborating Centre for the Prevention of @entity14 .

@entity1 @entity4310 @entity1127 @entity4511 @entity5 @entity2838 @entity517 @entity876 @entity6523 @entity74 @entity14 @entity1412 @entity694
Heritable and genetic factors pertinent to @entity694 can be divided into three categories: inherited syndromes, @entity74 , and molecular genetics. @entity1412 ( @entity1412 ) and @entity4511 ( @entity4511 ) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic @entity6523 . @entity694 occurs at a young age in both diseases unless the colon is removed. @entity2838 and @entity1412 are @entity74 with a less dramatic, but definite, increased risk for @entity694 . These four @entity1412 syndromes together account for less than 1% of cases of @entity694 . @entity14 is a dominantly inherited form of @entity694 characterized by an early age of onset and a predilection for proximal @entity5 . Multiple primary @entity5 are frequently observed and one or several @entity6523 are often present in affected individuals; 4-6% of @entity694 cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of @entity1 with @entity694 have a twofold to threefold increased risk of having @entity694 . More recent studies have found a similar risk among relatives of those with @entity6523 . Studies of @entity694 and @entity6523 in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to @entity1127 growth and finally @entity694 . Molecular studies have begun to elucidate the genetic mechanisms of @entity694 at the DNA level. The germinal mutation of @entity1412 and @entity4511 has been localized to the long arm of chromosome 5. Tissue samples from "random" @entity6523 and @entity694 have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in @entity1127 and @entity5 tissues is probably at the same locus as the germinal mutation of @entity1412 . There is evidence that this locus normally regulates expression of the @entity517 oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, @entity876 . Appropriate screening starting at a relatively young age is necessary to prevent @entity4310 . Screening is also indicated in close relatives of those with nonsyndromic or common @entity694 in view of the moderately increased risk for @entity694 in this group.(ABSTRACT TRUNCATED AT 400 WORDS)
