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Characterization of gene-environment interactions for colorectal cancer susceptibility loci.

Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC... Full description

Journal Title: Cancer research April 15, 2012, Vol.72(8), pp.2036-2044
Main Author: Hutter, Carolyn M
Other Authors: Chang-Claude, Jenny , Slattery, Martha L , Pflugeisen, Bethann M , Lin, Yi , Duggan, David , Nan, Hongmei , Lemire, Mathieu , Rangrej, Jagadish , Figueiredo, Jane C , Jiao, Shuo , Harrison, Tabitha A , Liu, Yan , Chen, Lin S , Stelling, Deanna L , Warnick, Greg S , Hoffmeister, Michael , Küry, Sébastien
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1538-7445 ; DOI: 10.1158/0008-5472.CAN-11-4067
Link: http://search.proquest.com/docview/1015753800/?pq-origsite=primo
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title: Characterization of gene-environment interactions for colorectal cancer susceptibility loci.
format: Article
creator:
  • Hutter, Carolyn M
  • Chang-Claude, Jenny
  • Slattery, Martha L
  • Pflugeisen, Bethann M
  • Lin, Yi
  • Duggan, David
  • Nan, Hongmei
  • Lemire, Mathieu
  • Rangrej, Jagadish
  • Figueiredo, Jane C
  • Jiao, Shuo
  • Harrison, Tabitha A
  • Liu, Yan
  • Chen, Lin S
  • Stelling, Deanna L
  • Warnick, Greg S
  • Hoffmeister, Michael
  • Küry, Sébastien
subjects:
  • Colorectal Neoplasms–Genetics
  • Diet–Genetics
  • Gene-Environment Interaction–Genetics
  • Genetic Predisposition to Disease–Genetics
  • Genotype–Genetics
  • Humans–Genetics
  • Polymorphism, Single Nucleotide–Genetics
ispartof: Cancer research, April 15, 2012, Vol.72(8), pp.2036-2044
description: Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P(interaction) = 1.3 × 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.
language: eng
source:
identifier: E-ISSN: 1538-7445 ; DOI: 10.1158/0008-5472.CAN-11-4067
fulltext: fulltext
issn:
  • 15387445
  • 1538-7445
url: Link


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titleCharacterization of gene-environment interactions for colorectal cancer susceptibility loci.
creatorHutter, Carolyn M ; Chang-Claude, Jenny ; Slattery, Martha L ; Pflugeisen, Bethann M ; Lin, Yi ; Duggan, David ; Nan, Hongmei ; Lemire, Mathieu ; Rangrej, Jagadish ; Figueiredo, Jane C ; Jiao, Shuo ; Harrison, Tabitha A ; Liu, Yan ; Chen, Lin S ; Stelling, Deanna L ; Warnick, Greg S ; Hoffmeister, Michael ; Küry, Sébastien
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ispartofCancer research, April 15, 2012, Vol.72(8), pp.2036-2044
identifierE-ISSN: 1538-7445 ; DOI: 10.1158/0008-5472.CAN-11-4067
subjectColorectal Neoplasms–Genetics ; Diet–Genetics ; Gene-Environment Interaction–Genetics ; Genetic Predisposition to Disease–Genetics ; Genotype–Genetics ; Humans–Genetics ; Polymorphism, Single Nucleotide–Genetics
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descriptionGenome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P(interaction) = 1.3 × 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.
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titleCharacterization of gene-environment interactions for colorectal cancer susceptibility loci.
authorHutter, Carolyn M ; Chang-Claude, Jenny ; Slattery, Martha L ; Pflugeisen, Bethann M ; Lin, Yi ; Duggan, David ; Nan, Hongmei ; Lemire, Mathieu ; Rangrej, Jagadish ; Figueiredo, Jane C ; Jiao, Shuo ; Harrison, Tabitha A ; Liu, Yan ; Chen, Lin S ; Stelling, Deanna L ; Warnick, Greg S ; Hoffmeister, Michael ; Küry, Sébastien
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date2012-04-15