Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition.
Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.
Agudo
Antonio
A
Unit of Epidemiology, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Av. Gran Via s/n km 2.7, 08907 Barcelona, Spain. a.agudo@iconcologia.net
Sala
Núria
N
Pera
Guillem
G
Capellá
Gabriel
G
Berenguer
Antonio
A
García
Nadia
N
Palli
Domenico
D
Boeing
Heiner
H
Del Giudice
Giuseppe
G
Saieva
Calogero
C
Carneiro
Fatima
F
Berrino
Franco
F
Sacerdote
Carlotta
C
Tumino
Rosario
R
Panico
Salvatore
S
Berglund
Göran
G
Simán
Henrik
H
Stenling
Roger
R
Hallmans
Göran
G
Martínez
Carmen
C
Bilbao
Roberto
R
Barricarte
Aurelio
A
Navarro
Carmen
C
Quirós
José R
JR
Allen
Naomi
N
Key
Tim
T
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Linseisen
Jakob
J
Nagel
Gabriele
G
Overvad
Kim
K
Tjonneland
Anne
A
Olsen
Anja
A
Bueno-de-Mesquita
H Bas
HB
Boshuizen
Hendriek C
HC
Peeters
Petra H
PH
Numans
Mattijs E
ME
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Trichopoulou
Antonia
A
Lund
Eiliv
E
Offerhaus
Johan
J
Jenab
Mazda
M
Ferrari
Pietro
P
Norat
Teresa
T
Riboli
Elio
E
González
Carlos A
CA
D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D002273:Carcinogens / Q000378:metabolism*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D052756:Nutritional Sciences; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics
D002273:Carcinogens; D011084:Polycyclic Aromatic Hydrocarbons; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase