Clinical-alimentary tractIncreased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms☆
Section snippets
Study population
The subjects in this study came from a multicenter, case-control study of esophageal and gastric cancer conducted in 3 geographic areas of the United States with population-based tumor registries.16 Population-based controls were frequency matched by 5-year age group and sex, and were selected by random-digit dialing and Health Care Financing Administration roster sampling as previously described.16 Genomic DNA was obtained from peripheral blood samples that had been collected at some of the
Results
Demographic and risk-factor characteristics of the subjects with cancer and the controls (Table 2) were similar to those reported in the previous study.16
Among controls, the alleles at all of the individual loci studied were in Hardy-Weinberg equilibrium, with nominally nonsignificant χ2 values (Table 3). Nevertheless, only 9 (4%) had the homozygous variant genotype of IL-1B-511, whereas 16 (7%) were expected based on allele frequencies (Hardy-Weinberg χ2 = 5.6; P = 0.07, 2 df). Based on
Discussion
We have identified a proinflammatory profile of genetic polymorphisms in IL-1B, IL-1RN, IL-10, and TNF-A associated with an increased risk of gastric cancer that was limited to noncardia tumors. No associations were seen with cancers of the gastric cardia or esophagus. The IL-1 gene cluster polymorphisms were associated with gastric cancer in 2 previous reports.11, 22 The ORs are similar in all 3 studies (all in predominantly white populations), underscoring the central role of IL-1β in the
References (43)
- et al.
Helicobacter pylori gastritis and gastric physiology
Gastroenterol Clin North Am
(2000) - et al.
Helicobacter pylori as a risk factor for cancer
Baillieres Clin Gastroenterol
(1995) - et al.
Interleukin 1β polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan
Gastroenterology
(2002) - et al.
Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1β production in Helicobacter pylori infection
Gastroenterology
(2002) - et al.
Interleukin 1β and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma
Gastroenterology
(2001) - et al.
CagA-positive strains of Helicobacter pylori may protect against Barrett’s esophagus
Am J Gastroenterol
(2000) - et al.
The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease
Gastroenterology
(1998) - et al.
Estimates of the worldwide incidence of 25 major cancers in 1990
Int J Cancer
(1999) Hypothesisthe changing relationships of Helicobacter pylori and humans: implications for health and disease
J Infect Dis
(1999)- et al.
Rising incidence of adenocarcinoma of the esophagus and gastric cardia
JAMA
(1991)
Changing patterns in the incidence of esophageal and gastric carcinoma in the United States
Cancer
Role of Helicobacter pylori cagA(+) strains and specific host immune responses on the development of premalignant and malignant lesions in the gastric cardia
Int J Cancer
Helicobacter pylori and gastrointestinal tract adenocarcinomas
Nat Rev Cancer
Cancer genetics
Nature
Genetics and the common cancers
Eur J Cancer
Interleukin-1 polymorphisms associated with increased risk of gastric cancer
Nature
The importance of interleukin 1beta in Helicobacter pylori associated disease
Gut
Cytokine gene polymorphism in human disease: on-line databases
Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia
J Natl Cancer Inst
An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma
Cancer Res
Comparison of three methods for single nucleotide polymorphism typing for DNA bank studiessequence-specific oligonucleotide probe hybridisation, TaqMan liquid phase hybridisation, and microplate array diagonal gel electrophoresis (MADGE)
Hum Mutat
Cited by (816)
Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology
2024, Expert Reviews in Molecular Medicine
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Supported in part by the National Cancer Institute. E.M.E. received a European H. pylori Study Group Research Fellowship from the Digestive Disorders Foundation (United Kingdom).
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The authors thank Drs. Heidi Rotterdam and Brian West for reviewing medical records and pathology slides for case eligibility, Dr. Denise Whitby for laboratory support, and Shelley Niwa for computing support.