CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).
Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position -160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case-control study (cases=245/controls=950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH1 gene polymorphisms. None of the CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies.
Jenab
Mazda
M
International Agency for Research on Cancer (IARC-WHO), Lyon, France. Jenab@iarc.fr
McKay
James D
JD
Ferrari
Pietro
P
Biessy
Carine
C
Laing
Stewart
S
Munar
Gabriel Maria Capella
GM
Sala
Núria
N
Peña
Salvador
S
Crusius
J B A
JB
Overvad
Kim
K
Jensen
Majken K
MK
Olsen
Anja
A
Tjonneland
Anne
A
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Kaaks
Rudolf
R
Linseisen
Jakob
J
Boeing
Heiner
H
Bergmann
Manuela M
MM
Trichopoulou
Antonia
A
Georgila
Christina
C
Psaltopoulou
Theodora
T
Mattiello
Amalia
A
Vineis
Paolo
P
Pala
Valeria
V
Palli
Domenico
D
Tumino
Rosario
R
Numans
Mattijs E
ME
Peeters
Petra H M
PH
Bueno-de-Mesquita
H Bas
HB
Lund
Eiliv
E
Ardanaz
Eva
E
Sánchez
Maria-Jose
MJ
Dorronsoro
Miren
M
Sanchez
Carmen Navarro
CN
Quirós
José Ramón
JR
Hallmans
Göran
G
Stenling
Roger
R
Manjer
Jonas
J
Régner
Sara
S
Key
Tim
T
Bingham
Sheila
S
Khaw
Kay-tee
KT
Slimani
Nadia
N
Rinaldi
Sabina
S
Boffetta
Paolo
P
Carneiro
Fátima
F
Riboli
Elio
E
Gonzalez
Carlos
C
D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D004812:Epidemiologic Methods; D005060:Europe; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000209:etiology*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins