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OC-052 Assessment of novel genetic polymorphisms and risk of upper gastrointestinal carcinoma
  1. G Hold1,
  2. E El-Omar2,
  3. W Chow3,
  4. H Risch4,
  5. M Gammon5,
  6. T Vaughan6,
  7. J Lissowska7,
  8. P Lochhead8,
  9. C Rabkin9,
  10. M Ng10
  1. 1Gastrointestinal Research Group, Aberdeen, UK
  2. 2Division of Medicine and Dentistry, Institute of Medical Sciences, Aberdeen, UK
  3. 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  4. 4Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
  5. 5Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
  6. 6Program in Epidemiology, Fred Hutchinson Cancer Research Center, School of Public Health, University of Washington, Seattle, Washington, USA
  7. 7Division of Cancer Epidemiology and Prevention, Cancer Centre and M Sklodowska Curie Institute of Oncology, Warsaw, Poland
  8. 8Division of Medicine and Dentistry, Aberdeen University, Aberdeen, UK
  9. 9Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  10. 10Division of Medicine and Dentistry, Yale University School of Medicine, New Haven, Connecticut, USA

Abstract

Introduction Upper gastrointestinal malignancies comprising gastric and oesophageal cancers remain a major global health problem. Recently, genome wide association studies have been used to identify risk factors for several diseases. Four SNPs identified at chromosome regions 8q24 and 9p24 (rs6983267, rs10505477, rs1447295 and rs719725) have been shown to increase risk of various solid tumours including prostate and colorectal cancer, but have not been studied in the context of upper GI cancer.

Methods Two case-control studies were used to assess SNP frequency: Study 1- a gastric cancer case-control study derived from a Caucasian population in Warsaw, Poland with DNA available from 312 non-cardia gastric adenocarcinoma patients and 419 controls, Study 2- a multicentre oesophageal and gastric cancer study from the US with DNA available from 307 subjects with gastric adenocarcinoma, 159 subjects with oesophageal cancer and 211 population controls. DNA was genotyped by 5′ nuclease PCR assay. Hardy-Weinberg equilibrium of alleles at individual loci was assessed using χ2 test. OR with Cornfield 95% CIs were computed by logistic regression using Stata V.7.0 software.

Results Genotyping and statistical analysis of the 4 SNPs was completed on 765 cases and 583 controls. Individuals carrying the C/C genotype of rs1447295 had an elevated risk for non-cardia gastric cancer (OR 1.57, 95% CI 1.03 to 2.45). Individuals carrying the A/A genotype of rs1447295 had an increased risk of squamous cell oesophageal cancer (OR 7.4, 95% CI 1.4 to 49). None of the other three SNPs tested in this study showed any statistically significant associations.

Conclusion The association between the rs1447295 SNP and risks of gastric and oesophageal cancer are novel and offer an opportunity to explore the genetic basis of these malignancies. Our study has extended the genetic link between the 8q24 region and risk of yet another group of solid tumours. Extensive efforts should focus on evaluating the functional significance of this region in the context of the molecular pathogenesis of these malignancies.

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