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Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases

Huhn, Stefanie ; Bevier, Melanie ; Rudolph, Anja ; Pardini, Barbara ; Naccarati, Alessio ; Hein, Rebecca ; Hoffmeister, Michael ; Vodickova, Ludmila ; Novotny, Jan and Brenner, Hermann , et al. (2012) In BMC Medical Genetics 13(94).
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%... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Colorectal cancer, Nutrition, Complex diseases
in
BMC Medical Genetics
volume
13
issue
94
publisher
BioMed Central (BMC)
external identifiers
  • wos:000312458500001
  • scopus:84867018871
ISSN
1471-2350
DOI
10.1186/1471-2350-13-94
language
English
LU publication?
yes
id
9c5ccc42-f1f3-486f-bfb8-ed3f3308d80a (old id 3366344)
date added to LUP
2016-04-01 13:13:59
date last changed
2022-01-27 18:02:13
@article{9c5ccc42-f1f3-486f-bfb8-ed3f3308d80a,
  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 &lt;= 0.05), whereas carriers of the ancestral allele of ENPP1 rs1044498 had a decreased risk (OR 0.79; p &lt;= 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.}},
  author       = {{Huhn, Stefanie and Bevier, Melanie and Rudolph, Anja and Pardini, Barbara and Naccarati, Alessio and Hein, Rebecca and Hoffmeister, Michael and Vodickova, Ludmila and Novotny, Jan and Brenner, Hermann and Chang-Claude, Jenny and Hemminki, Kari and Vodicka, Pavel and Försti, Asta}},
  issn         = {{1471-2350}},
  keywords     = {{Colorectal cancer; Nutrition; Complex diseases}},
  language     = {{eng}},
  number       = {{94}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Medical Genetics}},
  title        = {{Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases}},
  url          = {{https://lup.lub.lu.se/search/files/3246240/3910468.pdf}},
  doi          = {{10.1186/1471-2350-13-94}},
  volume       = {{13}},
  year         = {{2012}},
}