title: Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
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 case-control 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 = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). 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.
authors: Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain. a.agudo@iconcologia.net
authors: Antonio
authors: A
authors: Agudo
authors: Catalina
authors: C
authors: Bonet
authors: Núria
authors: N
authors: Sala
authors: Xavier
authors: X
authors: Muñoz
authors: Núria
authors: N
authors: Aranda
authors: Ana
authors: A
authors: Fonseca-Nunes
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Marie Christine
authors: MC
authors: Boutron-Ruault
authors: Paolo
authors: P
authors: Vineis
authors: Salvatore
authors: S
authors: Panico
authors: Domenico
authors: D
authors: Palli
authors: Rosario
authors: R
authors: Tumino
authors: Sara
authors: S
authors: Grioni
authors: J Ramón
authors: JR
authors: Quirós
authors: Esther
authors: E
authors: Molina
authors: Carmen
authors: C
authors: Navarro
authors: Aurelio
authors: A
authors: Barricarte
authors: Saioa
authors: S
authors: Chamosa
authors: Naomi E
authors: NE
authors: Allen
authors: Kay-Tee
authors: KT
authors: Khaw
authors: H Bas
authors: HB
authors: Bueno-de-Mesquita
authors: Peter D
authors: PD
authors: Siersema
authors: Mattijs E
authors: ME
authors: Numans
authors: Antonia
authors: A
authors: Trichopoulou
authors: Pagona
authors: P
authors: Lagiou
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Rudof
authors: R
authors: Kaaks
authors: Federico
authors: F
authors: Canzian
authors: Heiner
authors: H
authors: Boeing
authors: Karina
authors: K
authors: Meidtner
authors: Mattias
authors: M
authors: Johansson
authors: Malin
authors: M
authors: Sund
authors: Jonas
authors: J
authors: Manjer
authors: Kim
authors: K
authors: Overvad
authors: Anne
authors: A
authors: Tjonneland
authors: Eiliv
authors: E
authors: Lund
authors: Elisabete
authors: E
authors: Weiderpass
authors: Mazda
authors: M
authors: Jenab
authors: Veronika
authors: V
authors: Fedirko
authors: G Johan A
authors: GJ
authors: Offerhaus
authors: Elio
authors: E
authors: Riboli
authors: Carlos A
authors: CA
authors: González
authors: Paula
authors: P
authors: Jakszyn
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002299:Cardia / Q000473:pathology; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics
references: J Natl Cancer Inst. 2003 Jan 15;95(2):154-9
references: 12529348
references: J Natl Cancer Inst. 2005 Jun 15;97(12):917-26
references: 15956653
references: J Natl Cancer Inst. 2006 Mar 1;98(5):345-54
references: 16507831
references: Cancer Causes Control. 2003 Aug;14(6):541-5
references: 12948285
references: Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2427-34
references: 17164366
references: Blood Rev. 2005 Mar;19(2):69-88
references: 15603911
references: Public Health Nutr. 2002 Dec;5(6B):1113-24
references: 12639222
references: Leuk Lymphoma. 2006 Nov;47(11):2331-4
references: 17107905
references: Carcinogenesis. 2006 Jul;27(7):1497-501
references: 16571648
references: Annu Rev Physiol. 2007;69:69-85
references: 17014365
references: Int J Cancer. 2006 Jan 15;118(2):518-20
references: 16003728
references: J Exp Clin Cancer Res. 2010 Mar 02;29:18
references: 20196837
references: Hepatology. 2010 Apr;51(4):1311-8
references: 20099304
references: Ann Oncol. 2012 May;23(5):1320-1324
references: 21917738
references: Cancer Sci. 2009 Jan;100(1):9-16
references: 19018762
references: Scand J Gastroenterol. 2007 May;42(5):618-27
references: 17454883
references: Dis Colon Rectum. 2012 Mar;55(3):337-44
references: 22469802
references: JAMA. 2001 May 2;285(17):2216-22
references: 11325323
references: Hepatology. 2007 Oct;46(4):1071-80
references: 17828789
references: Int J Cancer. 2012 Jun 1;130(11):2654-63
references: 21717452
references: J Natl Cancer Inst. 2008 Jul 16;100(14):976-7
references: 18612127
references: Int J Cancer. 2011 May 15;128(10):2326-34
references: 20669231
references: FEBS Lett. 2006 Nov 13;580(26):6195-8
references: 17064691
references: Annu Rev Physiol. 2001;63:119-39
references: 11181951
references: Scand J Gastroenterol. 2012 Feb;47(2):136-47
references: 22242613
references: Int J Cancer. 2012 May 15;130(10):2417-27
references: 21681742
references: Genet Med. 2007 Jul;9(7):479-83
references: 17666895
references: Carcinogenesis. 2007 Mar;28(3):685-90
references: 17052997
references: Cancer Epidemiol Biomarkers Prev. 2005 Jun;14(6):1460-3
references: 15941956
references: Dig Dis Sci. 2005 Mar;50(3):474-82
references: 15810629
references: Ann Hematol. 2010 Apr;89(4):375-84
references: 19806355
references: Nutr Rev. 2003 Jan;61(1):38-42
references: 12638463
references: Leuk Lymphoma. 2006 Nov;47(11):2269-70
references: 17107894