Huhn, Stefanie, Bevier, Melanie, Rudolph, Anja 
ORCID: 0000-0001-7520-2035, Pardini, Barbara ORCID: 0000-0001-9571-4257, Naccarati, Alessio ORCID: 0000-0001-5774-0905, Hein, Rebecca, Hoffmeister, Michael ORCID: 0000-0002-8307-3197, Vodickova, Ludmila, Novotny, Jan, Brenner, Hermann ORCID: 0000-0002-6129-1572, Chang-Claude, Jenny, Hemminki, Kari, Vodicka, Pavel ORCID: 0000-0003-2376-1243 and Foersti, Asta
(2012).
Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases.
BMC Med. Genet., 13.
LONDON:
BMC.
ISSN 1471-2350
Abstract
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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-481128 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1186/1471-2350-13-94 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | BMC Med. Genet. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 13 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date: | 2012 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | BMC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1471-2350 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/48112 |
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