Characterization of gene-environment interactions for colorectal cancer susceptibility loci

Carolyn M. Hutter, Jenny Chang-Claude, Martha L. Slattery, Bethann M. Pflugeisen, Yi Lin, David Duggan, Hongmei Nan, Mathieu Lemire, Jagadish Rangrej, Jane C. Figueiredo, Shuo Jiao, Tabitha A. Harrison, Yan Liu, Lin S. Chen, Deanna L. Stelling, Greg S. Warnick, Michael Hoffmeister, Sébastien Küry, Charles S. Fuchs, Edward Giovannucci & 26 others Aditi Hazra, Peter Kraft, David J. Hunter, Steven Gallinger, Brent W. Zanke, Hermann Brenner, Bernd Frank, Jing Ma, Cornelia M. Ulrich, Emily White, Polly A. Newcomb, Charles Kooperberg, Andrea Z. LaCroix, Ross L. Prentice, Rebecca D. Jackson, Robert E. Schoen, Stephen J. Chanock, Sonja I. Berndt, Richard B. Hayes, Bette J. Caan, John D. Potter, Li Hsu, Stéphane Bézieau, Andrew T. Chan, Thomas J. Hudson, Ulrike Peters

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

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 antiinflammatory 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.

Original languageEnglish (US)
Pages (from-to)2036-2044
Number of pages9
JournalCancer Research
Volume72
Issue number8
DOIs
StatePublished - Apr 15 2012
Externally publishedYes

Fingerprint

Gene-Environment Interaction
Colorectal Neoplasms
Vegetables
Single Nucleotide Polymorphism
Genome-Wide Association Study
Dietary Calcium
Folic Acid
Meat
Aspirin
Meta-Analysis
Case-Control Studies
Fruit
Body Mass Index
Anti-Inflammatory Agents
Chromosomes
Smoking
Alcohols
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hutter, C. M., Chang-Claude, J., Slattery, M. L., Pflugeisen, B. M., Lin, Y., Duggan, D., ... Peters, U. (2012). Characterization of gene-environment interactions for colorectal cancer susceptibility loci. Cancer Research, 72(8), 2036-2044. https://doi.org/10.1158/0008-5472.CAN-11-4067

Characterization of gene-environment interactions for colorectal cancer susceptibility loci. / 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; Fuchs, Charles S.; Giovannucci, Edward; Hazra, Aditi; Kraft, Peter; Hunter, David J.; Gallinger, Steven; Zanke, Brent W.; Brenner, Hermann; Frank, Bernd; Ma, Jing; Ulrich, Cornelia M.; White, Emily; Newcomb, Polly A.; Kooperberg, Charles; LaCroix, Andrea Z.; Prentice, Ross L.; Jackson, Rebecca D.; Schoen, Robert E.; Chanock, Stephen J.; Berndt, Sonja I.; Hayes, Richard B.; Caan, Bette J.; Potter, John D.; Hsu, Li; Bézieau, Stéphane; Chan, Andrew T.; Hudson, Thomas J.; Peters, Ulrike.

In: Cancer Research, Vol. 72, No. 8, 15.04.2012, p. 2036-2044.

Research output: Contribution to journalArticle

Hutter, CM, Chang-Claude, J, Slattery, ML, Pflugeisen, BM, Lin, Y, Duggan, D, Nan, H, Lemire, M, Rangrej, J, Figueiredo, JC, Jiao, S, Harrison, TA, Liu, Y, Chen, LS, Stelling, DL, Warnick, GS, Hoffmeister, M, Küry, S, Fuchs, CS, Giovannucci, E, Hazra, A, Kraft, P, Hunter, DJ, Gallinger, S, Zanke, BW, Brenner, H, Frank, B, Ma, J, Ulrich, CM, White, E, Newcomb, PA, Kooperberg, C, LaCroix, AZ, Prentice, RL, Jackson, RD, Schoen, RE, Chanock, SJ, Berndt, SI, Hayes, RB, Caan, BJ, Potter, JD, Hsu, L, Bézieau, S, Chan, AT, Hudson, TJ & Peters, U 2012, 'Characterization of gene-environment interactions for colorectal cancer susceptibility loci', Cancer Research, vol. 72, no. 8, pp. 2036-2044. https://doi.org/10.1158/0008-5472.CAN-11-4067
Hutter CM, Chang-Claude J, Slattery ML, Pflugeisen BM, Lin Y, Duggan D et al. Characterization of gene-environment interactions for colorectal cancer susceptibility loci. Cancer Research. 2012 Apr 15;72(8):2036-2044. https://doi.org/10.1158/0008-5472.CAN-11-4067
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 ; Fuchs, Charles S. ; Giovannucci, Edward ; Hazra, Aditi ; Kraft, Peter ; Hunter, David J. ; Gallinger, Steven ; Zanke, Brent W. ; Brenner, Hermann ; Frank, Bernd ; Ma, Jing ; Ulrich, Cornelia M. ; White, Emily ; Newcomb, Polly A. ; Kooperberg, Charles ; LaCroix, Andrea Z. ; Prentice, Ross L. ; Jackson, Rebecca D. ; Schoen, Robert E. ; Chanock, Stephen J. ; Berndt, Sonja I. ; Hayes, Richard B. ; Caan, Bette J. ; Potter, John D. ; Hsu, Li ; Bézieau, Stéphane ; Chan, Andrew T. ; Hudson, Thomas J. ; Peters, Ulrike. / Characterization of gene-environment interactions for colorectal cancer susceptibility loci. In: Cancer Research. 2012 ; Vol. 72, No. 8. pp. 2036-2044.
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abstract = "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 antiinflammatory 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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T1 - Characterization of gene-environment interactions for colorectal cancer susceptibility loci

AU - Hutter, Carolyn M.

AU - Chang-Claude, Jenny

AU - Slattery, Martha L.

AU - Pflugeisen, Bethann M.

AU - Lin, Yi

AU - Duggan, David

AU - Nan, Hongmei

AU - Lemire, Mathieu

AU - Rangrej, Jagadish

AU - Figueiredo, Jane C.

AU - Jiao, Shuo

AU - Harrison, Tabitha A.

AU - Liu, Yan

AU - Chen, Lin S.

AU - Stelling, Deanna L.

AU - Warnick, Greg S.

AU - Hoffmeister, Michael

AU - Küry, Sébastien

AU - Fuchs, Charles S.

AU - Giovannucci, Edward

AU - Hazra, Aditi

AU - Kraft, Peter

AU - Hunter, David J.

AU - Gallinger, Steven

AU - Zanke, Brent W.

AU - Brenner, Hermann

AU - Frank, Bernd

AU - Ma, Jing

AU - Ulrich, Cornelia M.

AU - White, Emily

AU - Newcomb, Polly A.

AU - Kooperberg, Charles

AU - LaCroix, Andrea Z.

AU - Prentice, Ross L.

AU - Jackson, Rebecca D.

AU - Schoen, Robert E.

AU - Chanock, Stephen J.

AU - Berndt, Sonja I.

AU - Hayes, Richard B.

AU - Caan, Bette J.

AU - Potter, John D.

AU - Hsu, Li

AU - Bézieau, Stéphane

AU - Chan, Andrew T.

AU - Hudson, Thomas J.

AU - Peters, Ulrike

PY - 2012/4/15

Y1 - 2012/4/15

N2 - 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 antiinflammatory 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.

AB - 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 antiinflammatory 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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