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Genome-wide investigation of gene-environment interactions in colorectal cancer

Siegert, Sabine ; Hampe, Jochen ; Schafmayer, Clemens ; von Schoenfels, Witigo ; Egberts, Jan-Hendrik ; Försti, Asta LU ; Chen, Bowang ; Lascorz, Jesus ; Hemminki, Kari LU and Franke, Andre , et al. (2013) In Human Genetics 132(2). p.219-231
Abstract
Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene-environment (G x E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level. To this end, we adopted a two-tiered approach comprising a case-only screening stage I (314 cases) and a case-control validation stage II (259 cases, 1,002 controls). Interactions with the smallest p value in stage I were verified in stage II using multiple logistic regression... (More)
Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene-environment (G x E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level. To this end, we adopted a two-tiered approach comprising a case-only screening stage I (314 cases) and a case-control validation stage II (259 cases, 1,002 controls). Interactions with the smallest p value in stage I were verified in stage II using multiple logistic regression analysis adjusted for sex and age. In addition, we specifically studied known CRC-associated SNPs for possible G x E interactions. Upon adjustment for sex and age, and after allowing for multiple testing, however, only a single SNP (rs1944511) was found to be involved in a statistically significant interaction, namely with overweight (multiplicity-corrected p = 0.042 in stage II). Several other G x E interactions were nominally significant but failed correction for multiple testing, including a previously reported interaction between rs9929218 and alcohol consumption that also emerged in our candidate SNP study (nominal p = 0.008). Notably, none of the interactions identified in our genome-wide analysis was with a previously reported CRC-associated SNP. Our study therefore highlights the potential of an "agnostic" genome-wide approach to G x E analysis. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Genetics
volume
132
issue
2
pages
219 - 231
publisher
Springer
external identifiers
  • wos:000313518900010
  • scopus:84874772535
  • pmid:23114982
ISSN
1432-1203
DOI
10.1007/s00439-012-1239-2
language
English
LU publication?
yes
id
00d2387e-8418-43b8-9700-ce065d405591 (old id 3470440)
date added to LUP
2016-04-01 13:56:58
date last changed
2022-02-12 00:00:11
@article{00d2387e-8418-43b8-9700-ce065d405591,
  abstract     = {{Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene-environment (G x E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level. To this end, we adopted a two-tiered approach comprising a case-only screening stage I (314 cases) and a case-control validation stage II (259 cases, 1,002 controls). Interactions with the smallest p value in stage I were verified in stage II using multiple logistic regression analysis adjusted for sex and age. In addition, we specifically studied known CRC-associated SNPs for possible G x E interactions. Upon adjustment for sex and age, and after allowing for multiple testing, however, only a single SNP (rs1944511) was found to be involved in a statistically significant interaction, namely with overweight (multiplicity-corrected p = 0.042 in stage II). Several other G x E interactions were nominally significant but failed correction for multiple testing, including a previously reported interaction between rs9929218 and alcohol consumption that also emerged in our candidate SNP study (nominal p = 0.008). Notably, none of the interactions identified in our genome-wide analysis was with a previously reported CRC-associated SNP. Our study therefore highlights the potential of an "agnostic" genome-wide approach to G x E analysis.}},
  author       = {{Siegert, Sabine and Hampe, Jochen and Schafmayer, Clemens and von Schoenfels, Witigo and Egberts, Jan-Hendrik and Försti, Asta and Chen, Bowang and Lascorz, Jesus and Hemminki, Kari and Franke, Andre and Nothnagel, Michael and Noethlings, Ute and Krawczak, Michael}},
  issn         = {{1432-1203}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{219--231}},
  publisher    = {{Springer}},
  series       = {{Human Genetics}},
  title        = {{Genome-wide investigation of gene-environment interactions in colorectal cancer}},
  url          = {{http://dx.doi.org/10.1007/s00439-012-1239-2}},
  doi          = {{10.1007/s00439-012-1239-2}},
  volume       = {{132}},
  year         = {{2013}},
}