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Shared ancestral su...
Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases
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Huhn, Stefanie (author)
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Bevier, Melanie (author)
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Rudolph, Anja (author)
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Pardini, Barbara (author)
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Naccarati, Alessio (author)
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Hein, Rebecca (author)
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Hoffmeister, Michael (author)
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Vodickova, Ludmila (author)
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Novotny, Jan (author)
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Brenner, Hermann (author)
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Chang-Claude, Jenny (author)
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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Vodicka, Pavel (author)
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- Försti, Asta (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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(creator_code:org_t)
- 2012-10-05
- 2012
- English.
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13:94
- Related links:
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https://portal.resea... (primary) (free)
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http://dx.doi.org/10... (free)
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https://bmcmedgenet....
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background: The majority of non-syndromic colorectal cancers (CRCs) can be described as a complex disease. A two-stage case-control study on CRC susceptibility was conducted to assess the influence of the ancestral alleles in the polymorphisms previously associated with nutrition-related complex diseases. Methods: In stage I, 28 single nucleotide polymorphisms (SNPs) were genotyped in a hospital-based Czech population (1025 CRC cases, 787 controls) using an allele-specific PCR-based genotyping system (KASPar (R)). In stage II, replication was carried out for the five SNPs with the lowest p values. The replication set consisted of 1798 CRC cases and 1810 controls from a population-based German study (DACHS). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between genotypes and CRC risk were estimated using logistic regression. To identify signatures of selection, Fay-Wu's H and Integrated Haplotype Score (iHS) were estimated. Results: In the Czech population, carriers of the ancestral alleles of AGT rs699 and CYP3A7 rs10211 showed an increased risk of CRC (OR 1.26 and 1.38, respectively; two-sided p <= 0.05), whereas carriers of the ancestral allele of ENPP1 rs1044498 had a decreased risk (OR 0.79; p <= 0.05). For rs1044498, the strongest association was detected in the Czech male subpopulation (OR 0.61; p=0.0015). The associations were not replicated in the German population. Signatures of selection were found for all three analyzed genes. Conclusions: Our study showed evidence of association for the ancestral alleles of polymorphisms in AGT and CYP3A7 and for the derived allele of a polymorphism in ENPP1 with an increased risk of CRC in Czechs, but not in Germans. The ancestral alleles of these SNPs have previously been associated with nutrition-related diseases hypertension (AGT and CYP3A7) and insulin resistance (ENPP1). Future studies may shed light on the complex genetic and environmental interactions between different types of nutrition-related diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Colorectal cancer
- Nutrition
- Complex diseases
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Huhn, Stefanie
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Bevier, Melanie
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Rudolph, Anja
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Pardini, Barbara
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Naccarati, Aless ...
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Hein, Rebecca
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show more...
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Hoffmeister, Mic ...
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Vodickova, Ludmi ...
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Novotny, Jan
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Brenner, Hermann
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Chang-Claude, Je ...
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Hemminki, Kari
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Vodicka, Pavel
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Försti, Asta
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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BMC Medical Gene ...
- By the university
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Lund University