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Genome-wide investi...
Genome-wide investigation of gene-environment interactions in colorectal cancer
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Siegert, Sabine (author)
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Hampe, Jochen (author)
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Schafmayer, Clemens (author)
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von Schoenfels, Witigo (author)
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Egberts, Jan-Hendrik (author)
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- Försti, Asta (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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Chen, Bowang (author)
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Lascorz, Jesus (author)
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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Franke, Andre (author)
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Nothnagel, Michael (author)
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Noethlings, Ute (author)
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Krawczak, Michael (author)
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(creator_code:org_t)
- 2012-11-02
- 2013
- English.
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In: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 132:2, s. 219-231
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Siegert, Sabine
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Hampe, Jochen
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Schafmayer, Clem ...
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von Schoenfels, ...
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Egberts, Jan-Hen ...
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Försti, Asta
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show more...
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Chen, Bowang
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Lascorz, Jesus
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Hemminki, Kari
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Franke, Andre
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Nothnagel, Micha ...
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Noethlings, Ute
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Krawczak, Michae ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Human Genetics
- By the university
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Lund University