Clinical characterization and mutation spectrum in patients with familial adenomatous polyposis in China.

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. Patients with FAP are screened for germline mutations of two genes, APC and MUTYH. However, limited data exist on the clinical characterization and genotypic spectrum of FAP in China. This study was aimed to determine APC and MUTYH mutational status in a small cohort of FAP probands in China and to characterize the genotype-phenotype correlation in mutated patients. METHODS: Mutation screening of 46 unrelated probands was performed using multigene panels by next-generation sequencing. Clinical data of the index were used to assess genotype-phenotype correlations. RESULTS: Overall, 42 out of 46 (91.30%) unrelated probands found mutations, including 35 (76.09%) with APC mutations, 3 (6.52%) with MUTYH mutations, and 4 (8.70%) with both APC and MUTYH mutations. Ten APC genetic alterations variants were novel. The hereditary pattern of the family with both APC and MUTYH mutations was autosomal dominant inheritance. Upper gastrointestinal polyp was the most common extracolonic manifestations. The onset time for patients with both APC and MUTYH mutations was earlier than MUTYH mutation carriers and similar to APC mutation carriers. But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC mutation carriers and similar to MUTYH mutation carriers. CONCLUSION: In this study, we show the importance of using multigene panels that allow for a parallel comprehensive screening. We suggest that genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analyses simultaneously.

Detection of a heterozygous germline APC mutation in a three-generation family with familial adenomatous polyposis using targeted massive parallel sequencing in Vietnam.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary syndrome characterised by the development of hundreds to thousands of adenomatous colonic polyps during the second decade of life. FAP is caused by germ line mutations in the adenomatous polyposis coli (APC) gene located on chromosome 5q21-22. CASE PRESENTATION: A 36-year-old female was presented with 100-1000 adenomatous colonic polyps, typical of classic FAP symptoms. Genetic testing using massively parallel sequencing identified a 5-bp deletion (c.3927_3931delAAAGA) which causes frameshift (p.Glu1309Aspfs) and creates a premature stop codon, resulting in the replacement of the last 1535 amino acids of APC by five incorrect amino acids. Two of the proband's four siblings also exhibited classic FAP symptoms and carried the same 5-bp heterozygous deletion in the APC gene. One of the proband's two nephews also tested positive for this mutation but has not been examined by endoscopy due to his young age. CONCLUSIONS: We reported here for the first time the use of massively parallel sequencing (MPS)-based genetic testing to identify a germline mutation within a three-generation Vietnamese family. This mutation is most likely responsible for the development of FAP.

A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review.

Familial adenomatous polyposis (FAP), an autosomal dominant disease, is a colon cancer predisposition syndrome that manifests as a large number of adenomatous polyps. Mutations in the Adenomatous polyposis coli (APC) gene are responsible for the majority of cases of FAP. The purpose of the present study was to report the clinical features of a Chinese family with FAP and screen for novel mutations using the targeted next­generation sequencing technology. Among the 29 family members, 12 were diagnosed of FAP. Based on an established filtering strategy and data analyses, along with confirmation by Sanger sequencing and co­segregation, a novel frameshift mutation c.1317delA (p.Ala440LeufsTer14) in exon 10 of the APC gene was identified. To the best of our knowledge, this mutation has not been reported prior to the present study. In addition, it was correlated with extra­colonic phenotypes featuring duodenal polyposis and sebaceous cysts in this family. This novel frameshift mutation causing FAP not only expands the germline mutation spectrum of the APC gene in the Chinese population, but it also increases the understanding of the phenotypic and genotypic correlations of FAP, and may potentially lead to improved genetic counseling and specific treatment for families with FAP in the future.

Features of Patients With Hereditary Mixed Polyposis Syndrome Caused by Duplication of GREM1 and Implications for Screening and Surveillance.

Hereditary mixed polyposis syndrome is a rare colon cancer predisposition syndrome caused by a duplication of a noncoding sequence near the gremlin 1, DAN family BMP antagonist gene (GREM1) originally described in Ashkenazi Jews. Few families with GREM1 duplications have been described, so there are many questions about detection and management. We report 4 extended families with the duplication near GREM1 previously found in Ashkenazi Jews; 3 families were identified at cancer genetic clinics in Israel and 1 family was identified in a cohort of patients with familial colorectal cancer. Their clinical features include extracolonic tumors, onset of polyps in adolescence, and rapid progression of some polyps to advanced adenomas. One family met diagnostic criteria for Lynch syndrome. Expansion of the hereditary mixed polyposis syndrome phenotype can inform surveillance strategies for carriers of GREM1 duplications.

Clinicopathological features of a kindred with SCG5-GREM1-associated hereditary mixed polyposis syndrome.

Since first characterized in 1997, patients with hereditary mixed polyposis syndrome (HMPS) have been difficult to identify because of lack of well-established diagnostic criteria. Recently, HMPS was found to be caused by a duplication on chromosome 15 spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. Clinical testing for the duplication is available; however, the clinical characteristics of hereditary mixed polyposis to support testing are ill defined. The clinicopathological findings of 10 HMPS patients with confirmed germline SCG5-GREM1 duplication were reviewed. Mean age at presentation was 33.3 years. Fifty-one colonoscopies yielded 207 polyp specimens, all of which were reexamined. Adenomas (n = 80) and a fairly unique polyp composed of a mixture of hyperplastic polyp and inflammatory polyp-type changes (n = 74) were the most common findings; however, other polyps, including hyperplastic (n = 28), mixed inflammatory polyp/adenoma (n = 8), inflammatory polyp (n = 7), prolapse-type polyp (n = 6), and lymphoid aggregates (n = 4), were encountered. None of the patients developed colorectal malignancy during surveillance, demonstrated extracolonic manifestations, or underwent colectomy on follow-up (mean, 26.2 years). SCG5-GREM1 duplication-associated polyposis is characterized by a few polyps per endoscopy with a mixture of phenotypes, most commonly adenoma and nondysplastic mixed hyperplastic/inflammatory polyps. Nine of 10 patients had at least 1 mixed hyperplastic-inflammatory polyp, which is the characteristic lesion of SCG5-GREM1 duplication-associated HMPS.

A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a Chinese family with familial adenomatous coli.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease manifesting as colorectal cancer in middle-aged patients. Mutations of the adenomatous polyposis coli (APC) gene contribute to both FAP and sporadic or familial colorectal carcinogenesis. Here we describe the identification of the causative APC gene defects associated with FAP in a Chinese pedigree. All patients with FAP were diagnosed by their combination of clinical features, family history, colonoscopy, and pathology examinations. Blood samples were collected and genomic DNA was extracted. Mutation analysis of APC was conducted by targeted next-generation sequencing, long-range PCR and Sanger sequencing. A novel mutation in exon 14-15(c.1936-2148 del) and intron 14 of the APC gene was demonstrated in all FAP patients and was absent in unaffected family members. This novel deletion causing FAP in Chinese kindred expands the germline mutation spectrum of the APC gene in the Chinese population.

Clinical characterization and mutation spectrum in Hispanic families with adenomatous polyposis syndromes.

Several genetically defined hereditary colorectal cancer (CRC) syndromes are associated with colonic polyposis including familial adenomatous polyposis (FAP) and MUTYH adenomatous polyposis (MAP). Limited data exists on the clinical characterization and genotypic spectrum of polyposis syndromes among Hispanics. To describe the phenotype and genotype of Puerto Rican Hispanic patients with FAP and MUTYH and compare with other ethnic and racial groups. Probands were identified from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Recruited individuals completed risk factors, medical, and family history questionnaires and underwent genetic testing for genotype analysis. Frequency analysis, Chi square, Fisher's exact and Wilcoxon rank-sum tests were used for statistical analysis methods. A total of 31 FAP (from 19 families) and 13 MAP (from 13 families) Hispanic patients recruited from the PURIFICAR were evaluated. Among the FAP cases, mean age at diagnosis was 27.6 (range 9-71 years); 67.7 % cases had more than 100 polyps and 41.9 % had upper gastrointestinal polyps. Among the 19 FAP families, there were 77 affected FAP individuals and 26 colorectal cancer cases. Genetic mutations were available for 42.2 % of FAP families; all mutations identified were unique. Surgeries were reported in 31 cases; 14 (45.2 %) prophylactic surgeries and 6 (19.4 %) therapeutic surgeries for management of CRC. Among MAP cases, mean age at diagnosis was 53 (range 34-76 years). Genetic analysis revealed homozygous biallelic mutations (G382D) in 53.8 %, compound heterozygous mutations (G382/Y165C) in 23 %, and non-G382/Y165C monoallelic mutations in 23 %. Familial cancer registries should be promoted as vehicles for detection, education and follow up of families at-risk of acquiring familial cancers. PURIFICAR is the first and only familial cancer registry in Puerto Rico providing these services to families affected with familial cancer syndromes promoting education, testing and surveillance of at-risk family members, and focusing on cancer prevention efforts. The fact that only 40 % of FAP patients had access to genetic testing stresses the need to promote the establishment of policies supporting genetic testing coverage by medical insurance companies in order to provide patients with the highest standard of care to prevent cancer. Furthermore, our results suggest that Hispanics may have uncommon mutations in adenomatous polyposis related genes, which emphasize the need for full gene sequencing to establish genetic diagnosis.

Novel insertion mutation p.Asp610GlyfsX23 in APC gene causes familial adenomatous polyposis in Chinese families.

OBJECTIVE: The aim of the study was to identify the causative gene defects associated with familial adenomatous polyposis (FAP) in two Chinese pedigrees. METHODS: The diagnosis of FAP patients was confirmed by clinical manifestations, family histories, colonoscopy and pathology examinations. Blood samples were collected and genomic DNA was extracted. The mutation analysis of the adenomatous polyposis coli (APC) and human mutY homolog (MUTYH) genes was conducted by direct polymerase chain reaction (PCR) sequencing and multiplex ligation-dependent probe amplification (MLPA). RESULTS: In pedigree A, the results of direct PCR sequencing revealed a heterozygous insertion mutation at codon 610 in exon 15 of APC gene (c.1828_1829insG), which resulted in frameshift change (p.Asp610GlyfsX23) in all 4 patients, but was absent in the unaffected familial members and controls. In pedigree B, we didn't identify that causative mutations cosegregated with the clinical phenotype in the APC and MUTYH genes. CONCLUSIONS: We identified a novel insertion mutation as the pathogenic gene of FAP in Chinese population, which could enrich the germline mutation spectrum of APC gene, and the prophylactic proctocolectomy for the mutation carrier in family should be considered.

Adenomatous Polyposis Coli, mismatch repair, and microsatellite instability in colorectal cancer based on different locations.

AIM: to examine the protein expression negative (PEN) of Adenomatous Polyposis Coli (APC), Mismatch Repair (MMR), and Microsatellite Instability (MSI) status of colorectal cancer (CRC), and establish a comparison of those molecular characteristics in CRC location among Indonesian patients in Adam Malik Hospital, Pirngadi Hospital, and other hospitals within the network of Faculty of Medicine University of Sumatera Utara Medan Indonesia. METHODS: this prospective study was conducted from April to December 2012. Fresh tissues were obtained from colorectal tumor patients. The APC-PEN, MMR (MLH1, MSH2, PMS2, MSH6)-PEN, were assessed by immunohistochemistry, and MSI by PCR using 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346, D17S250), as independent variables. The tumour locations as dependent variables were divided into proximal colon (caecum, ascending colon, transverse colon); distal colon (splenic flexure, descending colon, sigmoid) and rectum. The comparative study were done by bivariate and multivariate analysis. RESULTS: there were 77 cases of colorectal adenocarsinoma. MMR-PEN was found in 54 of 77 (70.1%). MLH1-PEN was different between distal colon and rectal cancer (p=0.008); MSH6-PEN was different between proximal colon and rectal cancer (p= 0.020). Multivariate analysis showed: MLH1-PEN was related to cancer location (p=0.006) with OR 0.12 (95% CI 0.026-0.547). It had 0.12 times probability to be found in distal than rectum. MLH1-PEN had 10 times higher probability to be found in proximal than in distal (p=0.037). MSH6-PEN was related to the location (p=0.026) with OR 0.165 (95% CI 0.034-0.803), and had 0.165 times probability to be found in proximal than rectum; and 11 times higher probability in distal than proximal colon (p=0.043). APC-PEN was related to the location (p=0.020), with OR 6.897 (95% CI 1.359-34.995), and 6.89 times higher probability in distal than in rectum, with other variables controlled. MSI-H was found in 29 of 77 (37.7%) and MSI-L/MSS in 48 (62.3%). The proportion of MSI-H displayed a tendency to occur in proximal rather than in distal colon or rectal cancer. CONCLUSION: the underlying carcinogenic pathway or molecular background differs according to the cancer locations of CRC patients in this region. MLH1-PEN was prominent in proximal colon cancer, MSH6-PEN in distal colon and rectal cancer, and APC-PEN in distal colon respectively.

Racial differences in measures of obesity and risk of colon adenoma.

Obesity is an established risk factor for several malignancies. However, the specific measurement of obesity most relevant to colon neoplasia is still debated, and evidence has suggested gender and racial differences in this measurement. In this study, we sought to compare which measurement--BMI, waist circumference (WC), waist-to-hip ratio (WHR) or waist-to-height ratio (WHtR)--is most strongly associated with development of colon adenomas, a precursor of colon cancer, and to investigate differences in this association between racial groups. We confirmed the strong association between WHR, as a measure of central obesity, and development of colon neoplasia. In our overall analysis, patients in the highest WHR quartile showed a substantial increase in risk of colon adenomas compared to patients in the lowest WHR quartile (odds ratio (OR) = 1.82, 95% confidence interval (CI): 1.12-2.71, P(trend) = 0.0017). In stratified analyses, we noted that strongly associated obesity measures in European Americans were WC (OR = 2.38, 95% CI = 1.45-3.92, P(trend) = 0.0004) and BMI (OR = 2.18, 95% CI = 1.37-3.49, P(trend) = 0.0015), whereas in African Americans, WHR was the strongest and the only obesity measure statistically significantly associated with adenoma risk (OR = 2.12, 95% CI = 1.05-4.30, P(trend) = 0.025). Our data highlight the importance of obesity in the development of early colon neoplasia and suggest substantial racial differences in the measures of obesity most strongly associated with risk of colon adenomas.

APC gene mutations in Chinese familial adenomatous polyposis patients.

AIM: To study the characteristics of APC (adenomatous polyposis coli) gene germline mutation in Chinese patients with familial adenomatous polyposis (FAP). METHODS: APC gene from 14 FAP families was amplified by polymerase chain reaction (PCR) and underwent direct sequencing to determine the micromutation type. For the samples without micromutation, the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification (MLPA). RESULTS: There were gene micromutations in 9 families with a micromutation detection rate of 64.3% (9/14), including 6 frameshift mutations (66.7%), 1 nonsense mutation (11.1%) and 2 splicing mutations (22.2%). Large fragment deletions were detected by MLPA in 2 families. The total mutation detection rate of micromutations and large fragment deletions was 78.6% (11/14). CONCLUSION: The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.

Proximal shift in the distribution of adenomatous polyps in Korea over the past ten years.

BACKGROUND/AIMS: Several reports have suggested a trend of right-side shift of colorectal cancer; however, there were only a few studies on the chronologic changes in the distribution of adenomatous polyps. We aimed to study the changes in the distribution of colorectal adenomatous polyps over the past ten years. METHODOLOGY: We reviewed medical records of patients who underwent a colonoscopy at Yonsei University Severance Hospital, Seoul, Korea between January 1996 and December 2005. Patients who had an adenomatous polyp with a diameter of at least 5mm were included. Of these, patients with a history of colon resection, colorectal cancer, colorectal polyp, inflammatory bowel disease, HNPCC, or familial adenomatous polyposis were excluded. RESULTS: A total of 2,498 patients and 4,591 adenomatous polyps were included in this study. Analysis with respect to number of patients showed significant increases in the proportion of patients with adenomatous polyp on the proximal colon, from 48.5% to 66.3% (p<0.001). Analysis with respect to number of polyps revealed that the proportion of adenomatous polyps on the proximal colon significantly increased from 48.9% to 62.3% (p<0.001). CONCLUSIONS: The proportion of adenomatous polyp on the proximal colon significantly increased over the past 10 years.

Restorative proctocolectomy. Does ethnicity affect outcome?

OBJECTIVE: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is well-established in the management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). We review outcome of pouch surgery from a single centre, comparing non-South Asian and South Asian Caucasian populations. METHOD: Patients undergoing RPC for UC and FAP during a 10-year period between January 1997 and January 2007 were identified from hospital records. Data were collected retrospectively from case notes on early and long-term results. RESULTS: A total of 107 patients underwent pouch formation for UC (94%) or FAP (6%) and 22 (21%) were from the Asian subcontinent. Eighty-seven (81%) underwent a three-stage procedure and 20 (19%) a two-stage procedure. Postoperative complications occurred in 40 (37%) patients, being major in 11 (10%) patients with relaparotomy required in 9 (8%) with no difference between South Asian and non-South Asian Caucasian patients. Long-term pouch function, with a median of five times over 24 h (range 2-15), was similar between the two groups. The incidence of pouchitis was 57 (53%) and this was significantly greater in the South Asian population [17/21 (77%); 39/86 (46%); P = 0.006]. CONCLUSION: Surgical results were similar in South Asian and non-South Asian Caucasian patients, but the incidence of pouchitis was greater in the former group.

First genetic analysis in Tunisian familial adenomatous polyposis probands.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the development of hundreds to thousands of adenomatous polyps in colon and rectum. The APC gene (adenomatous polyposis coli) is considered as the major mutated gene in FAP. It has been shown that biallelic germline mutations in the base-excision-repair gene MYH can be responsible for a recessive inheritance of adenomatous polyposis (AP). This study is the first Tunisian genetic analysis on AP patients. Multiplex ligation-dependent probe amplification (MLPA) was used to screen the APC gene for large genomic rearrangements. The total APC and MYH exon sequences and exon-intron edges were sequenced in an effort to detect germline mutations, four were explored. Mutations were detected in four patients that fulfil the clinical criteria of AP. Three mutations were found in the APC gene, of which two were novel (c.1636_1639delAGTG and c.2514 G>T) and all gave rise to a truncated APC protein. The missense G382D mutation, already described in north and south European populations was found in the MYH gene at the homozygous state in the fourth patient with moderate AP. Our preliminary study provides a basis for implementation of genetic counselling for AP.

Clinical features of familial adenomas polyps in Chinese and establishment of its immortal lymphocyte cell lines.

AIM: To reserve the rare Chinese familial adenomas polyp (FAP) family resource and to investigate the clinical features of FAP in Chinese for its diagnosis. METHODS: Clinical features of patients with FAP were investigated. If there is any question, their medical records were verified. Blood sample was taken and lymphocyte immortal cell lines were established with modified EB-transformation methods. Congenital hypertrophy of retinal pigment epithelium (CHRPE) was checked by an experienced ophthalmologist. RESULTS: Twenty seven families including 21 classical FAP (CFAP) families, 3 attenuated FAP (AFAP) families, and 3 suspected AFAP families were investigated. A total of 116 lymphocyte immortal cell lines were established from 26 families. In all the FAP families, colorectal cancer occurred at the mean age of 42.84 years. Of the 16 families checked, 15 (93.75%) had CHRPE. The mean number of patients suffering from colorectal neoplasm was 3.14 in CFAP families and 2.0 in AFAP families (P<0.01). The mean oldest age at diagnosis of FAP was 41.75 years in CFAP families, and 58.67 years in AFAP families, respectively (P<0.01). Mean age of development of colorectal cancer was 42.23 in CFAP and 57.33 years old in AFAP (P<0.01). Mean of the earliest age at diagnosis of FAP was 29.95 years in the FAP families with a positive family history and 46.80 years in the FAP families with a negative family history (P < 0.01). The ratio of extra-intestinal tumors to colorectal neoplasms was different in the two kinds of families with positive and negative family history (P<0.01). CONCLUSION: Additional use of ciclosporin will effectively improve to establish lymphocyte immortal cell lines with modified EB- transformation methods. In Chinese FAP, there was a high frequency of CHRPE , and a later age at diagnosis and a later age of development of colorectal cancer in AFAP. And earlier age at diagnosis in FAP with positive family history was also found that will help to diagnose various kinds of FAP in Chinese.

Juvenile polyp in Thai children--clinical and colonoscopic presentation.

BACKGROUND: The aim of this prospective study was to describe the clinical characteristics of colorectal polyp in Thai children. METHODS: From December 2002 to February 2005, children under 15 years of age presenting with rectal bleeding were prospectively enrolled. Demographic, clinical, and laboratory information was recorded. Location, number, characteristics, and histopathology of the polyps were noted. RESULTS: There were 32 patients with a mean age of 6.5 years. The most common presenting symptom was hematochezia, followed by prolapsing rectal mass and diarrhea. In 20 patients there was a single polyp, 6 had 2-4 polyps, and 6 were diagnosed with polyposis coli. Most of the polyps were located exclusively at the rectum and sigmoid colon. In only 7 cases were the polyps proximal to the rectosigmoid region. This included 6 patients who had polyps beyond the splenic flexure. All were juvenile polyps without evidence of adenomatous changes. Compared to those with isolated polyps, the patients with polyposis coli had a statistically significant incidence of right-sided polyps (P <0.001) and a history of prolapse of the rectal mass (P = 0.006). CONCLUSIONS: Because of the high prevalence of right-sided polyps and the concern about malignant transformation, colonoscopy should be considered as the initial evaluation in children with rectal bleeding.

Mesenteric desmoid tumors in Singapore familial adenomatous polyposis patients: clinical course and genetic profile in a predominantly Chinese population.

PURPOSE: This study examined the mutational profile of the adenomatous polyposis coli gene in relation to the development of desmoid tumors in familial adenomatous polyposis patients from a predominantly Chinese population. METHODS: This is a retrospective review of all patients with familial adenomatous polyposis coli from the Singapore Polyposis Registry. Identification of specific adenomatous polyposis coli gene mutation was performed and clinical course of associated desmoid disease obtained from case records and a computerized database. RESULTS: Two hundred five patients from 75 families afflicted with familial adenomatous polyposis coli were reviewed, with gene mutations identified in 107 patients. Of these, 23 (11.2 percent) developed desmoids. The male-to-female ratio was 1:1.3 and the ethnic distribution was Chinese (n=17) and Malay (n=6). Of the 92 patients with mutations 5' to codon 1444, 11 patients (12 percent) developed desmoids compared with 6 of 15 (40 percent) patients with adenomatous polyposis coli gene mutations 3' to codon 1444 (P<0.01). The clinical course of desmoid tumors can be divided into stable (n=11), variable (n=3), progressive (n=6), and aggressive growth (n=3). Only 3 (13 percent) patients with aggressive tumor growth required chemotherapy. There was no correlation between the site of mutation and the clinical progression of the desmoids. Seventy-four percent of these desmoids (17/23) developed at a mean interval of 2.98 years after restorative proctocolectomy, while only 30 percent (7/23) were diagnosed preoperatively or discovered during the initial surgery. The most common complications related to the mesenteric desmoids were intestinal obstruction (21.7 percent), ureteric obstruction (17.4 percent), and encasement of superior mesenteric vessels (13 percent). CONCLUSION: The clinical course of desmoids in an individual familial adenomatous polyposis patient remains unpredictable and no reliable genetic marker is available for prognostication in desmoid disease.

Racial and gender disparities in hereditary colorectal cancer risk assessment: the role of family history.

BACKGROUND: In this study, we aimed to examine racial/ethnic and gender differences in self-reported family cancer history knowledge in patients at high risk for hereditary colon cancer syndromes. METHODS: We performed retrospective analysis of all referrals to the University of Chicago High Risk Colon Cancer Clinic between 1995 and 2003. RESULTS: We found hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis in 17% and 9% of Whites, respectively, and 6% and 0% of Blacks, respectively. Unknown paternal history was found in 6.5% of Whites and 18.9% of Blacks (23% men, 11% women). CONCLUSIONS: Blacks and men had significantly decreased rates of paternal history cancer knowledge.

Singapore familial adenomatous polyposis (FAP) patients with classical adenomatous polyposis but undetectable APC mutations have accelerated cancer progression.

OBJECTIVES: Germline mutation in adenomatous polyposis coli (APC) is detected in up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this study, we evaluated clinical features and APC mutations of Singapore FAP patients and contrasted genotype-phenotype correlation with Caucasians from other regions of the world and between FAP patients with and without detectable APC mutations. METHODS: We screened 242 members from 57 unrelated FAP families using a combination of cDNA protein truncation test, multiplex ligation-dependent probe amplification, and differential expression techniques. RESULTS: APC germline mutations were detected in 50 families. In contrast to Caucasians, fundic gland polyposis in Singapore patients was associated with APC mutations throughout the coding region and osteomas were also not confined to codon 767-1573. There was also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative patients from four families with mixed (adenomatous/hyperplastic/atypical juvenile) polyps were subsequently reclassified as hereditary mixed polyposis syndrome (HMPS) patients. APC mutation-negative patients with classical adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations. These patients had a significantly older age at diagnosis (P < 0.001) and more colorectal cancers (P= 0.017) than patients with APC mutations. CONCLUSIONS: We achieved a 94% (50/53) APC mutation detection rate via a combination of techniques, suggesting that the current detection rate is probably not exhaustive. Singapore patients have some features similar to and other features distinct from Caucasians. Furthermore, APC mutation-negative patients have accelerated cancer progression that merits closer surveillance.

CT colonography in a Korean population with a high residue diet: comparison between wet and dry preparations.

AIM: To compare wet and dry preparation methods for computed tomography colonography (CTC) in terms of preparation quality, interpretation time, and diagnostic performance for polyp detection in a population with a high residue diet. MATERIALS AND METHODS: Eighty-six patients were divided into two groups. Group 1 (n=24) received a wet preparation of 4l polyethylene glycol (PEG) solution, and group 2 (n=62) received a dry preparation of phosphor-soda. Abnormal findings, including polyps, and the time required to interpret the CTC images in both groups were documented by a radiologist. CTC findings were compared to those of colonoscopy as a reference standard. Two radiologists evaluated the quality of CTC with regard to residual fluid, faeces, and colonic distension using a four-point scale in consensus. Statistical differences for residual fluid, faeces, distensibility on CTC, and interpretation time between the two groups were analysed. The diagnostic performance of CTC in both groups was also compared. RESULTS: One-hundred and ninety polyps in 70 patients were identified using colonoscopy. Regarding the quality of images produced the wet preparation was significantly better than the dry preparation (p<0.05). The average interpretation time was significantly shorter for the wet group (11.7 min) than the dry group (16.4 min) (p<0.05). For per-patient analysis, the positive predictive value (PPV) was significantly better for the wet (100%) than the dry group (79.6%; p=0.025). Sensitivities and PPV for >or=10 mm polyps were comparable between two groups (p>0.05). CONCLUSION: In a population with a high-residue diet, CTC with wet preparation can be interpreted in a time-efficient manner and is comparable with CTC with dry preparation.