[Show abstract][Hide abstract] ABSTRACT: Hyperplastic polyposis syndrome (HPS) confers an increased risk of colorectal cancer and is difficult to manage clinically. Because both polyps and resultant cancers display the CpG island methylator phenotype and mutation of the BRAF oncogene, and because sporadic cancers with these characteristics are associated with cigarette smoking, we hypothesized that cigarette smoking may predispose to the development of HPS.
This was a case-control study with two independent control series conducted at a tertiary hospital in Brisbane, Queensland, Australia. Cases comprised patients with HPS (n=32) recruited through the database of the Queensland Familial Bowel Registry, who satisfied the World Health Organization international classification for HPS. Cases were compared with colonoscopy controls (n=298) defined as consecutive patients undergoing colonoscopy for clinical indications, who were free from polyps. We also compared cases with a second set of population controls (n=645) selected at random from a population register serving the catchment area for cases. This was an observational study, and all participants completed a questionnaire to obtain a comprehensive smoking history.
The prevalence rate of current smoking was 47% in HPS patients, 17% in colonoscopy controls, and 12% in population controls. HPS patients were significantly more likely to be current smokers than were either colonoscopy controls (odds ratio (OR)=8.3, 95% confidence interval (CI): 3.0-22.9) or population controls (OR=12.7, 95% CI: 4.9-33.1).
Cigarette smoking is strongly associated with HPS, thus suggesting that smoking exposure may increase the expression of this condition. Further studies should examine the possible benefits of quitting smoking in HPS patients.
The American Journal of Gastroenterology 07/2010; 105(7):1642-7. DOI:10.1038/ajg.2009.757 · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP.
[Show abstract][Hide abstract] ABSTRACT: A family is presented with attenuated familial adenomatous polyposis of variable phenotype. The clinical features range from sparse right-sided polyposis and cancer in the proximal colon at the age of 34 to pan-colonic polyposis and cancer at the age of 68. Rectal sparing is common to all affected members. Heteroduplex analysis detected bands of altered mobility in exon 9 of the APC gene in all affected family members. Subsequently, a frameshift mutation was found in the alternatively spliced region of exon 9 at codon 398 which resulted in a stop signal 4 codons downstream. Alternatively spliced transcripts that delete the mutation were readily amplified from normal colonic mucosa and therefore create a mechanism for the attenuated phenotype seen in this family.
Human Mutation 01/1998; 11(6):450-5. DOI:10.1002/(SICI)1098-1004(1998)11:6<450::AID-HUMU5>3.0.CO;2-P · 5.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial adenomatous polyposis usually results in colonic polyposis with hundreds to thousands of polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and variable extracolonic features. Recent reports indicate that patients with distal mutations between codons 1445 and 1578 do not express CHRPE and have a high incidence of desmoid tumours.
The family studied has an unusual phenotype of sparse colonic polyposis but profuse upper gastrointestinal polyposis. Affected subjects do not have CHRPE.
The protein truncation test followed by sequencing identified a 2 base pair deletion at codon 1520 in the APC gene. This results in a frameshift creating a stop codon 13 codons downstream.
This family demonstrates that sparse colonic polyposis but severe upper tract polyposis may be associated with mutations between codons 1445 and 1578.
Study of duodenal and colonic polyps in further cases with mutations in this region is warranted. Such mutations may preferentially cause duodenal adenomas and desmoid tumours as somatic mutations in these tumours also occur in this region, unlike colorectal tumours where somatic mutations occur more proximally. This study emphasises the importance of screening the upper gastrointestinal tract even when the colonic disease is mild.
Gut 11/1997; 41(4):518-21. DOI:10.1136/gut.41.4.518 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In familial juvenile polyposis, multiple juvenile polyps occur throughout the colon. The genetic defect has not been characterized. The risk of colon cancer is increased, although the magnitude of the increased risk is controversial. The hypothesis of this study was that the genetic defect is within a tumor suppressor gene, possibly one already known to be inactivated in colorectal neoplasia.
Linkage analysis using the short tandem repeat polymorphism D5S346 was performed to determine if juvenile polyposis was linked to either APC (adenomatous polyposis coli) or MCC (mutated in colorectal carcinoma) genes within a single large family.
A family in which eight subjects have been affected by juvenile polyposis over three generations is described. Six affected subjects had colectomies in childhood, but the two who have so far survived beyond 35 years of age have developed adenocarcinoma of the jejunum. Within this family, linkage analysis excluded linkage of the juvenile polyposis trait to either APC or MCC.
In a family with juvenile polyposis with a clear predisposition to malignancy, including carcinoma of the jejunum, APC and MCC were not the defective genes causing the condition.