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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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keywords
Colorectal cancer, Nutrition, Complex diseases
in
BMC Medical Genetics
volume
13
issue
94
publisher
BioMed Central
external identifiers
  • wos:000312458500001
  • scopus:84867018871
ISSN
1471-2350
DOI
10.1186/1471-2350-13-94
language
English
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yes
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9c5ccc42-f1f3-486f-bfb8-ed3f3308d80a (old id 3366344)
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2013-02-01 06:57:23
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@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},
  keyword      = {Colorectal cancer,Nutrition,Complex diseases},
  language     = {eng},
  number       = {94},
  publisher    = {BioMed Central},
  series       = {BMC Medical Genetics},
  title        = {Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases},
  url          = {http://dx.doi.org/10.1186/1471-2350-13-94},
  volume       = {13},
  year         = {2012},
}