Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases

0383020 - ÚEM 2013 RIV GB eng J - Journal Article
Huhn, S. - Bevier, M. - Rudolph, A. - Pardini, Barbara - Naccarati, Alessio - Hein, R. - Hoffmeister, M. - Vodičková, Ludmila - Novotný, J. - Brenner, H. - Chang-Claude, J. - Vodička, Pavel - Hemminki, K. - Försti, A.
Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases.
BMC Medical Genetics. Roč. 13, č. 1 (2012), s. 94. E-ISSN 1471-2350
R&D Projects: GA ČR GAP304/10/1286; GA ČR GAP304/12/1585
Institutional research plan: CEZ:AV0Z50390512
Institutional support: RVO:68378041
Keywords : colorectal cancer * nutrition * complex diseases
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 2.536, year: 2012

The majority of 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. 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. 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 hed light on the complex genetic and environmental interactions between different types of nutrition-related diseases.
Permanent Link: http://hdl.handle.net/11104/0213092