Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry

Xuejuan Jiang, J. Esteban Castelao, David Vandenberg, Angel Carracedo, Carmen M. Redondo, David V. Conti, Jesus P. Paredes Cotoré, John D. Potter, Polly A. Newcomb, Michael N. Passarelli, Mark A. Jenkins, John L. Hopper, Steven Gallinger, Loic Le Marchand, María E. Martínez, Dennis J. Ahnen, John A. Baron, Noralane Morey Lindor, Robert W. Haile, Manuela Gago-Dominguez

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry. Materials and Methods: 23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression. Results: Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps. Conclusions: SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.

Original languageEnglish (US)
Article numbere60464
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 3 2013

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colorectal neoplasms
Colonic Neoplasms
Registries
Colorectal Neoplasms
Single Nucleotide Polymorphism
genetic variation
Genes
Anti-Inflammatory Agents
nonsteroidal anti-inflammatory agents
Smoking
Odds Ratio
odds ratio
Confidence Intervals
Population
Tobacco Products
confidence interval
Pharmaceutical Preparations
Logistics
Polyps
smoking (habit)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Jiang, X., Castelao, J. E., Vandenberg, D., Carracedo, A., Redondo, C. M., Conti, D. V., ... Gago-Dominguez, M. (2013). Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry. PLoS One, 8(4), [e60464]. https://doi.org/10.1371/journal.pone.0060464

Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry. / Jiang, Xuejuan; Castelao, J. Esteban; Vandenberg, David; Carracedo, Angel; Redondo, Carmen M.; Conti, David V.; Paredes Cotoré, Jesus P.; Potter, John D.; Newcomb, Polly A.; Passarelli, Michael N.; Jenkins, Mark A.; Hopper, John L.; Gallinger, Steven; Le Marchand, Loic; Martínez, María E.; Ahnen, Dennis J.; Baron, John A.; Lindor, Noralane Morey; Haile, Robert W.; Gago-Dominguez, Manuela.

In: PLoS One, Vol. 8, No. 4, e60464, 03.04.2013.

Research output: Contribution to journalArticle

Jiang, X, Castelao, JE, Vandenberg, D, Carracedo, A, Redondo, CM, Conti, DV, Paredes Cotoré, JP, Potter, JD, Newcomb, PA, Passarelli, MN, Jenkins, MA, Hopper, JL, Gallinger, S, Le Marchand, L, Martínez, ME, Ahnen, DJ, Baron, JA, Lindor, NM, Haile, RW & Gago-Dominguez, M 2013, 'Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry', PLoS One, vol. 8, no. 4, e60464. https://doi.org/10.1371/journal.pone.0060464
Jiang X, Castelao JE, Vandenberg D, Carracedo A, Redondo CM, Conti DV et al. Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry. PLoS One. 2013 Apr 3;8(4). e60464. https://doi.org/10.1371/journal.pone.0060464
Jiang, Xuejuan ; Castelao, J. Esteban ; Vandenberg, David ; Carracedo, Angel ; Redondo, Carmen M. ; Conti, David V. ; Paredes Cotoré, Jesus P. ; Potter, John D. ; Newcomb, Polly A. ; Passarelli, Michael N. ; Jenkins, Mark A. ; Hopper, John L. ; Gallinger, Steven ; Le Marchand, Loic ; Martínez, María E. ; Ahnen, Dennis J. ; Baron, John A. ; Lindor, Noralane Morey ; Haile, Robert W. ; Gago-Dominguez, Manuela. / Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry. In: PLoS One. 2013 ; Vol. 8, No. 4.
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AU - Carracedo, Angel

AU - Redondo, Carmen M.

AU - Conti, David V.

AU - Paredes Cotoré, Jesus P.

AU - Potter, John D.

AU - Newcomb, Polly A.

AU - Passarelli, Michael N.

AU - Jenkins, Mark A.

AU - Hopper, John L.

AU - Gallinger, Steven

AU - Le Marchand, Loic

AU - Martínez, María E.

AU - Ahnen, Dennis J.

AU - Baron, John A.

AU - Lindor, Noralane Morey

AU - Haile, Robert W.

AU - Gago-Dominguez, Manuela

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N2 - Background: Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry. Materials and Methods: 23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression. Results: Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps. Conclusions: SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.

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