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7 records – page 1 of 1.

3'-UTR poly(T/U) repeat of EWSR1 is altered in microsatellite unstable colorectal cancer with nearly perfect sensitivity.

https://arctichealth.org/en/permalink/ahliterature273744
Source
Fam Cancer. 2015 Sep;14(3):449-53
Publication Type
Article
Date
Sep-2015
Author
Johanna Kondelin
Sari Tuupanen
Alexandra E Gylfe
Mervi Aavikko
Laura Renkonen-Sinisalo
Heikki Järvinen
Jan Böhm
Jukka-Pekka Mecklin
Claus L Andersen
Pia Vahteristo
Esa Pitkänen
Lauri A Aaltonen
Source
Fam Cancer. 2015 Sep;14(3):449-53
Date
Sep-2015
Language
English
Publication Type
Article
Keywords
3' Untranslated Regions
Calmodulin-Binding Proteins - genetics
Colorectal Neoplasms - genetics
Denmark
Finland
Humans
Microsatellite Instability
Polyribonucleotides - genetics
RNA-Binding Proteins - genetics
Repetitive Sequences, Nucleic Acid
Abstract
Approximately 15% of colorectal cancers exhibit instability of short nucleotide repeat regions, microsatellites. These tumors display a unique clinicopathologic profile and the microsatellite instability status is increasingly used to guide clinical management as it is known to predict better prognosis as well as resistance to certain chemotherapeutics. A panel of five repeats determined by the National Cancer Institute, the Bethesda panel, is currently the standard for determining the microsatellite instability status in colorectal cancer. Recently, a quasimonomorphic mononucleotide repeat 16T/U at the 3' untranslated region of the Ewing sarcoma breakpoint region 1 gene was reported to show perfect sensitivity and specificity in detecting mismatch repair deficient colorectal, endometrial, and gastric cancers in two independent populations. To confirm this finding, we replicated the analysis in 213 microsatellite unstable colorectal cancers from two independent populations, 148 microsatellite stable colorectal cancers, and the respective normal samples by PCR and fragment analysis. The repeat showed nearly perfect sensitivity for microsatellite unstable colorectal cancer as it was altered in 212 of the 213 microsatellite unstable (99.5%) and none of the microsatellite stable colorectal tumors. This repeat thus represents the first potential single marker for detecting microsatellite instability.
PubMed ID
25930744 View in PubMed
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Desmoid tumor patients carry an elevated risk of familial adenomatous polyposis.

https://arctichealth.org/en/permalink/ahliterature273504
Source
J Surg Oncol. 2016 Feb;113(2):209-12
Publication Type
Article
Date
Feb-2016
Author
Laura Koskenvuo
Päivi Peltomäki
Laura Renkonen-Sinisalo
Annette Gylling
Taina T Nieminen
Ari Ristimäki
Anna Lepistö
Source
J Surg Oncol. 2016 Feb;113(2):209-12
Date
Feb-2016
Language
English
Publication Type
Article
Keywords
Adenomatous Polyposis Coli - diagnosis - epidemiology - genetics
Adolescent
Adult
Aged
Aged, 80 and over
Databases, Factual
Endoscopy, Gastrointestinal
Female
Fibromatosis, Aggressive - complications
Finland - epidemiology
Genes, APC
Humans
Male
Middle Aged
Mutation
Prospective Studies
Risk assessment
Risk factors
Abstract
The prevalence of desmoid tumors among patients with familial adenomatous polyposis (FAP) is at least 10%, and the prevalence of FAP among desmoid patients varies between 7.5-16%.
Data included 106 desmoid patients identified from the database of the Department of Pathology, Helsinki University Hospital, years 2000-2012. We evaluated the risk of FAP among patients by using endoscopy and we identified individuals with attenuated FAP by APC gene mutation test. We compared sporadic desmoid patients' and FAP patients' clinical characteristics.
Ten of 106 patients already had FAP diagnosis before the desmoid. Eleven patients had had FAP screening already earlier due to desmoid and three of them were found to have FAP. Total of 52 patients participated into prospective screening of FAP. No new cases of FAP were found. The risk of FAP among desmoid tumor patients was 4.8%. In the FAP desmoid group, there were more males and patients were younger than in the sporadic group. Intra-abdominal desmoids were more common in the FAP group.
Patients with desmoid carry an elevated risk of FAP and therefore screening is indicated. Asymptomatic patients with desmoid situated in extra truncal region may not need to be screened.
PubMed ID
26663236 View in PubMed
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.

https://arctichealth.org/en/permalink/ahliterature287622
Source
Int J Cancer. 2018 Feb 01;142(3):540-546
Publication Type
Article
Date
Feb-01-2018
Author
Tomas Tanskanen
Linda van den Berg
Niko Välimäki
Mervi Aavikko
Eivind Ness-Jensen
Kristian Hveem
Yvonne Wettergren
Elinor Bexe Lindskog
Neeme Tõnisson
Andres Metspalu
Kaisa Silander
Giulia Orlando
Philip J Law
Sari Tuupanen
Alexandra E Gylfe
Ulrika A Hänninen
Tatiana Cajuso
Johanna Kondelin
Antti-Pekka Sarin
Eero Pukkala
Pekka Jousilahti
Veikko Salomaa
Samuli Ripatti
Aarno Palotie
Heikki Järvinen
Laura Renkonen-Sinisalo
Anna Lepistö
Jan Böhm
Jukka-Pekka Mecklin
Nada A Al-Tassan
Claire Palles
Lynn Martin
Ella Barclay
Albert Tenesa
Susan M Farrington
Maria N Timofeeva
Brian F Meyer
Salma M Wakil
Harry Campbell
Christopher G Smith
Shelley Idziaszczyk
Tim S Maughan
Richard Kaplan
Rachel Kerr
David Kerr
Daniel D Buchanan
Aung K Win
John Hopper
Mark A Jenkins
Polly A Newcomb
Steve Gallinger
David Conti
Fredrick R Schumacher
Graham Casey
Jeremy P Cheadle
Malcolm G Dunlop
Ian P Tomlinson
Richard S Houlston
Kimmo Palin
Lauri A Aaltonen
Source
Int J Cancer. 2018 Feb 01;142(3):540-546
Date
Feb-01-2018
Language
English
Publication Type
Article
Keywords
Case-Control Studies
Cohort Studies
Colorectal Neoplasms - epidemiology - genetics
Estonia - epidemiology
Finland - epidemiology
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Registries
Abstract
Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p?=?2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p?=?1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate?
PubMed ID
28960316 View in PubMed
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Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome.

https://arctichealth.org/en/permalink/ahliterature166618
Source
Int J Cancer. 2007 Feb 15;120(4):821-4
Publication Type
Article
Date
Feb-15-2007
Author
Laura Renkonen-Sinisalo
Ralf Bützow
Arto Leminen
Pentti Lehtovirta
Jukka-Pekka Mecklin
Heikki J Järvinen
Author Affiliation
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Source
Int J Cancer. 2007 Feb 15;120(4):821-4
Date
Feb-15-2007
Language
English
Publication Type
Article
Keywords
Adult
Aged
Biopsy
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
Endometrial Neoplasms - pathology
Endosonography
Female
Finland
Follow-Up Studies
Genetic Predisposition to Disease
Humans
Middle Aged
Neoplasm Staging
Pelvis - ultrasonography
Population Surveillance
Registries
Risk factors
Abstract
The estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32-60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment.
PubMed ID
17096354 View in PubMed
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Systematic search for rare variants in Finnish early-onset colorectal cancer patients.

https://arctichealth.org/en/permalink/ahliterature262532
Source
Cancer Genet. 2015 Jan-Feb;208(1-2):35-40
Publication Type
Article
Author
Tomas Tanskanen
Alexandra E Gylfe
Riku Katainen
Minna Taipale
Laura Renkonen-Sinisalo
Heikki Järvinen
Jukka-Pekka Mecklin
Jan Böhm
Outi Kilpivaara
Esa Pitkänen
Kimmo Palin
Pia Vahteristo
Sari Tuupanen
Lauri A Aaltonen
Source
Cancer Genet. 2015 Jan-Feb;208(1-2):35-40
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Colorectal Neoplasms - epidemiology - genetics
Exome - genetics
Family Health
Finland - epidemiology
Gene Frequency
Genetic Predisposition to Disease - genetics
Genotype
Humans
Mutation
Sequence Analysis, DNA - methods
Young Adult
Abstract
The heritability of colorectal cancer (CRC) is incompletely understood, and the contribution of undiscovered rare variants may be important. In search of rare disease-causing variants, we exome sequenced 22 CRC patients who were diagnosed before the age of 40 years. Exome sequencing data from 95 familial CRC patients were available as a validation set. Cases with known CRC syndromes were excluded. All patients were from Finland, a country known for its genetically homogenous population. We searched for rare nonsynonymous variants with allele frequencies below 0.1% in 3,374 Finnish and 58,112 non-Finnish controls. In addition, homozygous and compound heterozygous variants were studied. No genes with rare loss-of-function variants were present in more than one early-onset CRC patient. Three genes (ADAMTS4, CYTL1, and SYNE1) harbored rare loss-of-function variants in both early-onset and familial CRC cases. Five genes with homozygous variants in early-onset CRC cases were found (MCTP2, ARHGAP12, ATM, DONSON, and ROS1), including one gene (MCTP2) with a homozygous splice site variant. All discovered homozygous variants were exclusive to one early-onset CRC case. Independent replication is required to associate the discovered variants with CRC. These findings, together with a lack of family history in 19 of 22 (86%) early-onset patients, suggest genetic heterogeneity in unexplained early-onset CRC patients, thus emphasizing the requirement for large sample sizes and careful study designs to elucidate the role of rare variants in CRC susceptibility.
PubMed ID
25749350 View in PubMed
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Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members.

https://arctichealth.org/en/permalink/ahliterature148800
Source
J Clin Oncol. 2009 Oct 1;27(28):4793-7
Publication Type
Article
Date
Oct-1-2009
Author
Heikki J Järvinen
Laura Renkonen-Sinisalo
Katja Aktán-Collán
Päivi Peltomäki
Lauri A Aaltonen
Jukka-Pekka Mecklin
Author Affiliation
Department of Surgery, University of Helsinki, FI-00029 HUS, Helsinki, Finland. Heikki.Jarvinen@hus.fi
Source
J Clin Oncol. 2009 Oct 1;27(28):4793-7
Date
Oct-1-2009
Language
English
Publication Type
Article
Keywords
Adaptor Proteins, Signal Transducing - genetics
Adolescent
Adult
Aged
Cause of Death
Colonoscopy
Colorectal Neoplasms - epidemiology - genetics - mortality
Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis - genetics
Female
Finland - epidemiology
Follow-Up Studies
Genetic Testing - methods
Genital Neoplasms, Female - epidemiology - genetics - mortality
Heterozygote
Humans
Incidence
Male
Middle Aged
MutS Homolog 2 Protein - genetics
Mutation
Neoplasms - epidemiology - genetics - mortality
Nuclear Proteins - genetics
Survival Rate
Time Factors
Young Adult
Abstract
Colonoscopies with polypectomies and endometrial biopsies with transvaginal ultrasonography, repeated at 2- to 3-year intervals, are performed for prevention or early detection of cancer in patients with DNA mismatch repair gene mutation causing Lynch syndrome. The long-term effectiveness of surveillance was evaluated in Lynch syndrome family members tested approximately 10 years ago.
Cancer incidence and survival were determined after an 11.5-year follow-up in 242 mutation-positive and 367 mutation-negative participants. These participants in 57 Lynch syndrome families with 14 different mutations were at 50% risk. The median age was 36 years (range, 18 to 72 years) in mutation carriers and 42 years (range, 18 to 72 years) in mutation-negative participants, and none had had cancer of the Lynch syndrome type.
Compliance was 95.9% for the colonic surveillance and 97.1% for the gynecologic surveillance. Colorectal cancer (CRC) occurred in 30 mutation-positive participants, and 74 participants had adenomas removed. Three patients died of CRC. Endometrial cancer (EC) occurred in 19 of 103 women at risk, and 48 women had prophylactic hysterectomy. Six of 112 women at risk had ovarian cancer. The overall cancer risk ratio (RR) in mutation carriers was 5.80 (95% CI, 3.4 to 9.5). Cancer mortality rate (RR = 2.28; 95% CI, 0.82 to 6.31) and overall death rate (RR = 1.26; 95% CI, 0.65 to 2.46) were not significantly increased.
Long-term compliance in surveillance for CRC and EC exceeded 95% in Lynch syndrome. All CRC deaths were not prevented as a result of noncompliance or missed lesions. Still, after 10 years of surveillance, no significant increase in mortality had occurred compared with mutation-negative relatives.
PubMed ID
19720893 View in PubMed
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Utility of computed tomographic colonography in surveillance for hereditary nonpolyposis colorectal cancer syndrome.

https://arctichealth.org/en/permalink/ahliterature165349
Source
Fam Cancer. 2007;6(1):135-40
Publication Type
Article
Date
2007
Author
Laura Renkonen-Sinisalo
Arto Kivisaari
Leena Kivisaari
Seppo Sarna
Heikki J Järvinen
Author Affiliation
Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, PL 340, 00029 HUS Helsinki, Finland. laura.renkonen-sinisalo@hus.fi
Source
Fam Cancer. 2007;6(1):135-40
Date
2007
Language
English
Publication Type
Article
Keywords
Adenomatous Polyps - diagnosis - radiography - surgery
Adult
Aged
Colonic Polyps - diagnosis - radiography - surgery
Colonography, Computed Tomographic
Colonoscopy
Colorectal Neoplasms - diagnosis - radiography - surgery
Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis - epidemiology - radiography
False Negative Reactions
Feasibility Studies
Female
Finland - epidemiology
Humans
Male
Mass Screening - methods
Middle Aged
Population Surveillance - methods
Rectal Diseases - diagnosis - epidemiology
Sensitivity and specificity
Abstract
Computed tomographic colonography (CTC) is suggested to be an alternative to colonoscopy as a surveillance tool in subjects with a high risk for colorectal cancer (CRC). To evaluate the utility of CTC we successively examined 78 subjects, all with a DNA mismatch repair gene mutation, by CTC and colonoscopy. We detected altogether 37 polyps or tumors in 28 subjects (prevalence 35.9%), adenomas in 13 subjects (16.7%), CRC in two (2.6%), and hyperplastic polyps in 13 (16.7%). A great majority of the polyps were diminutive. The per-patient sensitivity for detecting all lesions with CTC was 0.25 and 0.29 by two radiologists and the specificities 0.82 and 0.76. For lesions of 10 mm or larger the sensitivities were 0.6 and 1.0 and the specificities 0.96 by each examiner. Each diagnosed the two cancers correctly. We concluded that CTC has an acceptable accuracy for large lesions in the colon but the detection rate for small polyps is not comparable to that in colonoscopy. Therefore CTC remains a second choice in surveillance for use when colonoscopy for some reason is incomplete or unsuitable.
PubMed ID
17273816 View in PubMed
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7 records – page 1 of 1.