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Common variants in human CRC genes as low-risk alleles.

https://arctichealth.org/en/permalink/ahliterature98081
Source
Eur J Cancer. 2010 Apr;46(6):1041-8
Publication Type
Article
Date
Apr-2010
Author
Simone Picelli
Pawel Zajac
Xiao-Lei Zhou
David Edler
Claes Lenander
Johan Dalén
Fredrik Hjern
Nils Lundqvist
Ulrik Lindforss
Lars Påhlman
Kennet Smedh
Anders Törnqvist
Jörn Holm
Martin Janson
Magnus Andersson
Susanne Ekelund
Louise Olsson
Joakim Lundeberg
Annika Lindblom
Author Affiliation
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Source
Eur J Cancer. 2010 Apr;46(6):1041-8
Date
Apr-2010
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Alleles
Case-Control Studies
Colorectal Neoplasms - epidemiology - genetics
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genome-Wide Association Study
Genotype
Germ-Line Mutation - genetics
Humans
Male
Middle Aged
Penetrance
Polymorphism, Genetic
Risk factors
Sweden - epidemiology
Young Adult
Abstract
The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.
PubMed ID
20149637 View in PubMed
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PepT1 oligopeptide transporter (SLC15A1) gene polymorphism in inflammatory bowel disease.

https://arctichealth.org/en/permalink/ahliterature150812
Source
Inflamm Bowel Dis. 2009 Oct;15(10):1562-9
Publication Type
Article
Date
Oct-2009
Author
Marco Zucchelli
Leif Torkvist
Francesca Bresso
Jonas Halfvarson
Anna Hellquist
Francesca Anedda
Ghazaleh Assadi
Gunnar B Lindgren
Monika Svanfeldt
Martin Janson
Colin L Noble
Sven Pettersson
Maarit Lappalainen
Paulina Paavola-Sakki
Leena Halme
Martti Färkkilä
Ulla Turunen
Jack Satsangi
Kimmo Kontula
Robert Löfberg
Juha Kere
Mauro D'Amato
Author Affiliation
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Source
Inflamm Bowel Dis. 2009 Oct;15(10):1562-9
Date
Oct-2009
Language
English
Publication Type
Article
Keywords
Adult
Case-Control Studies
Cohort Studies
Colitis, Ulcerative - genetics
Crohn Disease - genetics
Female
Finland
Genotype
Humans
Male
Middle Aged
NF-kappa B - genetics - metabolism
Nod2 Signaling Adaptor Protein - genetics - metabolism
Polymorphism, Single Nucleotide - genetics
Sweden
Symporters - genetics
Abstract
Human polymorphisms affecting gut epithelial barrier and interactions with bacteria predispose to the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). The intestinal transporter PepT1, encoded by the SLC15A1 gene, mediates intracellular uptake of bacterial products that can induce inflammation and NF-kappaB activation upon binding to NOD2, a protein often mutated in CD. Hence, we tested SLC15A1 polymorphisms for association with IBD.
Twelve SLC15A1 single nucleotide polymorphisms (SNPs) were genotyped in 1783 individuals from 2 cohorts of Swedish and Finnish IBD patients and controls. An in vitro system was set up to evaluate the potential impact of SLC15A1 polymorphism on PepT1 transporter function by quantification of NOD2-mediated activation of NF-kappaB.
The common allele (C) of a coding polymorphism (rs2297322, Ser117Asn) was associated with CD susceptibility both in Sweden and in Finland, but with genetic effects in opposite directions (risk and protection, respectively). The best evidence of association was found in both populations when the analysis was performed on individuals not carrying NOD2 common risk alleles (Sweden allelic P = 0.0007, OR 1.97, 95% confidence interval [CI] 1.34-2.92; Finland genotype P = 0.0013, OR 0.63, 95% CI 0.44-0.90). The PepT1 variant encoded by the C allele (PepT1-Ser117) was associated with reduced signaling downstream of NOD2 (P
PubMed ID
19462432 View in PubMed
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