Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers.
BACKGROUND
We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia).


METHODS
The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR).


RESULTS
The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
Vineis
P
P
Imperial College London, London, UK. p.vineis@imperial.ac.uk
Veglia
F
F
Garte
S
S
Malaveille
C
C
Matullo
G
G
Dunning
A
A
Peluso
M
M
Airoldi
L
L
Overvad
K
K
Raaschou-Nielsen
O
O
Clavel-Chapelon
F
F
Linseisen
J P
JP
Kaaks
R
R
Boeing
H
H
Trichopoulou
A
A
Palli
D
D
Crosignani
P
P
Tumino
R
R
Panico
S
S
Bueno-De-Mesquita
H B
HB
Peeters
P H
PH
Lund
E
E
Gonzalez
C A
CA
Martinez
C
C
Dorronsoro
M
M
Barricarte
A
A
Navarro
C
C
Quiros
J R
JR
Berglund
G
G
Jarvholm
B
B
Day
N E
NE
Key
T J
TJ
Saracci
R
R
Riboli
E
E
Autrup
H
H
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D015238:Sulfotransferases / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D007527:Isoenzymes; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D005982:Glutathione Transferase; D015238:Sulfotransferases