Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

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Abstract

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested casecontrol study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI 1.031.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR 1.60, CI 1.162.21) and intestinal histological subtype (OR 1.82, CI 1.272.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

Details

Authors
  • Antonio Agudo
  • Catalina Bonet
  • Nuria Sala
  • Xavier Munoz
  • Nuria Aranda
  • Ana Fonseca-Nunes
  • Franoise Clavel-Chapelon
  • Marie Christine Boutron-Ruault
  • Paolo Vineis
  • Salvatore Panico
  • Domenico Palli
  • Rosario Tumino
  • Sara Grioni
  • J. Ramon Quiros
  • Esther Molina
  • Carmen Navarro
  • Aurelio Barricarte
  • Saioa Chamosa
  • Naomi E. Allen
  • Kay-Tee Khaw
  • H. Bas Bueno-de-Mesquita
  • Peter D. Siersema
  • Mattijs E. Numans
  • Antonia Trichopoulou
  • Pagona Lagiou
  • Dimitrios Trichopoulos
  • Rudof Kaaks
  • Federico Canzian
  • Heiner Boeing
  • Karina Meidtner
  • Mattias Johansson
  • Malin Sund
  • Kim Overvad
  • Anne Tjonneland
  • Eiliv Lund
  • Elisabete Weiderpass
  • Mazda Jenab
  • Veronika Fedirko
  • G. Johan A. Offerhaus
  • Elio Riboli
  • Carlos A. Gonzalez
  • Paula Jakszyn
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)1244-1250
JournalCarcinogenesis
Volume34
Issue number6
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes