Genetic predisposition to clinical manifestations in familial adenomatous polyposis with special reference to duodenal lesions

Abstract

Truncating APC gene mutation proximal to exon 9 may contribute to the less frequent development of duodenal adenomatosis in FAP, but severity and progression of duodenal adenomatosis do not seem to be determined by APC gene mutation alone.

Impact of Phospholipase A2 Group IIa Gene Polymorphism on Phenotypic Features of Patients with Familial Adenomatous Polyposis

“…13 Furthermore, the development of FGP was independent of the site of germline APC mutation. 12 These observations were confirmed in the present investigation. Furthermore, we could demonstrate that the contribution of SNP in PLA2g2a to the development of FGP remained to be significant even when H. pylori infection was taken into consideration.…”

“…[15][16][17][18][19][20][21][22][23] Although it should be noted that PTT applied in our study does not detect all mutations of APC and in fact the method missed 5 percent of APC mutation, we have previously shown a genotypephenotype correlation in Japanese patients with FAP by means of PTT. 12,24 We performed direct sequence for 37 of 55 patients; 10 of 37 patients were negative for PTT: 1 of the 10 patients with negative PTT had a missense mutation (data not shown). Among the ten patients with negative PTT result, direct sequence identified a missense mutation in one patient, whereas APC mutation remained undetermined in the other nine patients.…”

“…12 In brief, genomic DNA and mRNA were obtained from peripheral leukocytes and the latter was reverse-transcribed to cDNA. cDNA was amplified with two primer pairs by polymerase chain reaction (PCR) for proximal segments of the APC and DNA with four primer pairs for distal segments of the APC gene.…”

“…We previously reported the impacts of APC mutation and Helicobacter pylori infection on gastric lesions in FAP. 12,13 In that investigation, there was a close association between H. pylori infection and FGP. On the other hand, genetic background for the development of FGP has not been precisely elucidated to date.…”

APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations

“…In our study, advanced duodenal aVection and death of duodenal cancer were reported in 18 unrelated families with mutations spanning from codon 213 through codon 1,464. This is a relatively high frequency indicating that risk of duodenal adenomas is likely to be inXuenced by factors additional to APC, as have been suggested by others (Enomoto et al 2000;Matsumoto et al 2002).…”