Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms

Emad Munir El-Omar, C. S. Rabkin, M. D. Gammon, T. L. Vaughan, H. A. Risch, J. B. Schoenberg, J. L. Stanford, S. T. Mayne, J. Goedert, W. J. Blot, J. F. Fraumeni, W. H. Chow

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Abstract

Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o), IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were riot associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

Original languageEnglish
Pages (from-to)1193-1201
Number of pages8
JournalGastroenterology
Volume124
Issue number5
DOIs
Publication statusPublished - May 2003

Keywords

  • HELICOBACTER-PYLORI INFECTION
  • GASTROESOPHAGEAL REFLUX DISEASE
  • BARRETTS-ESOPHAGUS
  • ATROPHIC GASTRITIS
  • INTERLEUKIN-1 POLYMORPHISMS
  • CAGA(+) STRAINS
  • CARDIA
  • ACID
  • CARCINOMA
  • ADENOCARCINOMA

Cite this

El-Omar, E. M., Rabkin, C. S., Gammon, M. D., Vaughan, T. L., Risch, H. A., Schoenberg, J. B., ... Chow, W. H. (2003). Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology, 124(5), 1193-1201. https://doi.org/10.1016/S0016-5085(03)00157-4

Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. / El-Omar, Emad Munir; Rabkin, C. S.; Gammon, M. D.; Vaughan, T. L.; Risch, H. A.; Schoenberg, J. B.; Stanford, J. L.; Mayne, S. T.; Goedert, J.; Blot, W. J.; Fraumeni, J. F.; Chow, W. H.

In: Gastroenterology, Vol. 124, No. 5, 05.2003, p. 1193-1201.

Research output: Contribution to journalArticle

El-Omar, EM, Rabkin, CS, Gammon, MD, Vaughan, TL, Risch, HA, Schoenberg, JB, Stanford, JL, Mayne, ST, Goedert, J, Blot, WJ, Fraumeni, JF & Chow, WH 2003, 'Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms', Gastroenterology, vol. 124, no. 5, pp. 1193-1201. https://doi.org/10.1016/S0016-5085(03)00157-4
El-Omar, Emad Munir ; Rabkin, C. S. ; Gammon, M. D. ; Vaughan, T. L. ; Risch, H. A. ; Schoenberg, J. B. ; Stanford, J. L. ; Mayne, S. T. ; Goedert, J. ; Blot, W. J. ; Fraumeni, J. F. ; Chow, W. H. / Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. In: Gastroenterology. 2003 ; Vol. 124, No. 5. pp. 1193-1201.
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abstract = "Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o), IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95{\%} confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were riot associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.",
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author = "El-Omar, {Emad Munir} and Rabkin, {C. S.} and Gammon, {M. D.} and Vaughan, {T. L.} and Risch, {H. A.} and Schoenberg, {J. B.} and Stanford, {J. L.} and Mayne, {S. T.} and J. Goedert and Blot, {W. J.} and Fraumeni, {J. F.} and Chow, {W. H.}",
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T1 - Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms

AU - El-Omar, Emad Munir

AU - Rabkin, C. S.

AU - Gammon, M. D.

AU - Vaughan, T. L.

AU - Risch, H. A.

AU - Schoenberg, J. B.

AU - Stanford, J. L.

AU - Mayne, S. T.

AU - Goedert, J.

AU - Blot, W. J.

AU - Fraumeni, J. F.

AU - Chow, W. H.

PY - 2003/5

Y1 - 2003/5

N2 - Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o), IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were riot associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

AB - Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o), IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were riot associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

KW - HELICOBACTER-PYLORI INFECTION

KW - GASTROESOPHAGEAL REFLUX DISEASE

KW - BARRETTS-ESOPHAGUS

KW - ATROPHIC GASTRITIS

KW - INTERLEUKIN-1 POLYMORPHISMS

KW - CAGA(+) STRAINS

KW - CARDIA

KW - ACID

KW - CARCINOMA

KW - ADENOCARCINOMA

U2 - 10.1016/S0016-5085(03)00157-4

DO - 10.1016/S0016-5085(03)00157-4

M3 - Article

VL - 124

SP - 1193

EP - 1201

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 5

ER -