Advanced

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

Agudo, Antonio; Bonet, Catalina; Sala, Nuria; Munoz, Xavier; Aranda, Nuria; Fonseca-Nunes, Ana; Clavel-Chapelon, Franoise; Boutron-Ruault, Marie Christine; Vineis, Paolo and Panico, Salvatore, et al. (2013) In Carcinogenesis 34(6). p.1244-1250
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Carcinogenesis
volume
34
issue
6
pages
1244 - 1250
publisher
Oxford University Press
external identifiers
  • wos:000320271100008
  • scopus:84878972815
ISSN
0143-3334
DOI
10.1093/carcin/bgt045
language
English
LU publication?
yes
id
477bcf35-f230-4566-9ffc-8a77eba20468 (old id 3983115)
date added to LUP
2013-09-02 11:21:34
date last changed
2019-07-02 01:08:13
@article{477bcf35-f230-4566-9ffc-8a77eba20468,
  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.},
  author       = {Agudo, Antonio and Bonet, Catalina and Sala, Nuria and Munoz, Xavier and Aranda, Nuria and Fonseca-Nunes, Ana and Clavel-Chapelon, Franoise and Boutron-Ruault, Marie Christine and Vineis, Paolo and Panico, Salvatore and Palli, Domenico and Tumino, Rosario and Grioni, Sara and Ramon Quiros, J. and Molina, Esther and Navarro, Carmen and Barricarte, Aurelio and Chamosa, Saioa and Allen, Naomi E. and Khaw, Kay-Tee and Bas Bueno-de-Mesquita, H. and Siersema, Peter D. and Numans, Mattijs E. and Trichopoulou, Antonia and Lagiou, Pagona and Trichopoulos, Dimitrios and Kaaks, Rudof and Canzian, Federico and Boeing, Heiner and Meidtner, Karina and Johansson, Mattias and Sund, Malin and Manjer, Jonas and Overvad, Kim and Tjonneland, Anne and Lund, Eiliv and Weiderpass, Elisabete and Jenab, Mazda and Fedirko, Veronika and Offerhaus, G. Johan A. and Riboli, Elio and Gonzalez, Carlos A. and Jakszyn, Paula},
  issn         = {0143-3334},
  language     = {eng},
  number       = {6},
  pages        = {1244--1250},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study},
  url          = {http://dx.doi.org/10.1093/carcin/bgt045},
  volume       = {34},
  year         = {2013},
}