Novel mutations of the APC gene in familial adenomatous polyposis in Greek patients

Mihalatos, Markos; Danielides, Ioannis K.; Belogianni, J; Harokopos, E; Papadopoulou, Eirini; Kalimanis, G.; Tsiava, M; Triantafillidis, John K.; Kosmidis, P.; Fountzilas, George; Basdanis, G.; Agnantis, Niki J.; Yannoukakos, Drakoulis; Nasioulas, Georgios

doi:10.1016/s0165-4608(02)00723-9

Cited by 17 publications

(16 citation statements)

References 19 publications

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“…Among the 6 probands subjected to genetic analysis of the APC gene, 3 mutations (50%) were detected. Compared with previous studies [11,17,19,20,24,25], the mutation rate in this study is similar to those reported for Israelis (50.7%) and Czechs (45.4%), but lower than those for Greeks (83%), Finns (72%) and others (up to 95%). The mutation rates in the APC gene vary among different ethnic groups.…”

Section: Discussionsupporting

confidence: 84%

“…If left untreated, cancer inevitably develops at a median age of 39 years [2]. FAP is also associated with extracolonic manifestations including desmoids, osteomas, epidermoid cysts, congenital hypertrophy of the retinal pigment epithelium and other tumors (brain, thyroid and liver) [11,24]. APC, the gene responsible for FAP, was cloned in 1991 and was found to be located at chromosome 5q [3,12,18].…”

Section: Introductionmentioning

confidence: 99%

“…Over 600 different germ line mutations in APC have been documented using different techniques [11,31]. Subsequently, mutation spectra in FAP kindreds of different countries were established and showed highly variable results (30-80%), suggesting variation among different ethnic groups [5,6,11,17,19,24,25,29].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Analysis of the APC Gene in Taiwanese Familial Adenomatous Polyposis

Wei

Tsai-Wu

et al. 2004

J Biomed Sci

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Colorectal cancer has become the third leading cause of death from cancer in Taiwan. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of multiple adenomatous polyps in the colon and rectum. The gene responsible for FAP (APC) was cloned in 1991. Extensive analyses of the mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30–80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166, with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554–1556, which created a downstream stop codon (codon 1558). This study is the first to report mutation analysis in Taiwanese FAP probands.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Genetic Analysis of the APC Gene in Taiwanese Familial Adenomatous Polyposis

Wei

Tsai-Wu

et al. 2004

J Biomed Sci

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“…The functional significance of the Asp1822Val substitution is unknown, although this amino acid change is located in the center of a h-catenin down-regulation domain (18). The clinical relevance of this polymorphism is also uncertain and previous work suggests that Asp1822Val may either be a low-penetrance allele that increases risk of developing colorectal cancer (16) or a common polymorphism without clinical implication (19).…”

Section: Introductionmentioning

confidence: 99%

APC Asp1822Val and Gly2502Ser Polymorphisms and Risk of Colorectal Cancer and Adenoma

Tranah

Giovannucci

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene is an important initiating factor in the early stages of the adenoma-carcinoma sequence. The aim of this study was to investigate the two most common APC variants (Asp1822Val and Gly2502Ser) and their association with colorectal cancer and adenoma and whether these relationships are influenced by dietary and lifestyle factors. We analyzed 556 adenoma cases and 557 matched controls and 197 cancer cases and 490 matched controls nested within the Nurses' Health Study cohort, 274 cancer cases and 456 matched controls nested within the Physicians' Health Study cohort, and 375 adenoma cases and 724 matched controls nested within the Health Professionals Follow-up Study cohort. APC Asp1822Val and Gly2502Ser polymorphisms were not associated with risk of colorectal cancer or adenoma. For colorectal cancer, a significant interaction was found between Asp1822Val genotype and postmenopausal hormone (PMH) use among postmenopausal women (P interaction = 0.03). Current PMH use was associated with reduced risk overall and a statistically significant lower risk of colorectal cancer among carriers of one or two copies of the APC 1822Val allele (relative risk, 0.46; 95% confidence interval, 0.24-0.88) relative to wild-type never or past PMH users. Our results suggest that cigarette smoking, alcohol intake, and family history of colorectal cancer were positively associated and regular aspirin intake was inversely associated with colorectal adenoma in men and women. No gene-environment interactions were observed with these risk factors or with other dietary risk factors previously hypothesized to interact with the APC

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“…Clinical diagnosis of HNPCC is not always easy as there is no clear phenotype associated with the disorder as is the case with other cancer predisposition syndromes such as familial adenomatous polyposis (Mihalatos et al, 2003b). Besides the spectrum of cancers characteristic of HNPCC, MSI is considered as one of the hallmark diagnostic features of HNPCC-related cancers (Boland et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

hMSH2 is the most commonly mutated MMR gene in a cohort of Greek HNPCC patients

Apessos¹,

Mihalatos²,

Danielidis

et al. 2005

Br J Cancer

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Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A unique disease-causing mutation has been identified in seven out of nine (78%) families. The types of mutations identified are nonsense (five out of seven) (hMLH1: E557X, R226X; hMSH2: Q158X, R359X and R711X), a 2 bp deletion (hMSH2 1704_1705delAG) and a 2.2 kb Alu-mediated deletion encompassing exon 3 of the hMSH2 gene. The majority of mutations identified in this cohort are found in hMSH2 (77.7%). Furthermore, four of the mutations identified are novel. Finally, a number of novel benign variations were observed in both genes. This is the first report of HNPCC analysis in the Greek population, further underscoring the differences observed in the various geographic populations.

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Novel mutations of the APC gene in familial adenomatous polyposis in Greek patients

Cited by 17 publications

References 19 publications

Genetic Analysis of the APC Gene in Taiwanese Familial Adenomatous Polyposis

Genetic Analysis of the APC Gene in Taiwanese Familial Adenomatous Polyposis

APC Asp1822Val and Gly2502Ser Polymorphisms and Risk of Colorectal Cancer and Adenoma

hMSH2 is the most commonly mutated MMR gene in a cohort of Greek HNPCC patients

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