title: Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers.
abstract: 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.
authors.affiliation: Imperial College London, London, UK. p.vineis@imperial.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Vineis
authors.forename: F
authors.initials: F
authors.lastname: Veglia
authors.forename: S
authors.initials: S
authors.lastname: Garte
authors.forename: C
authors.initials: C
authors.lastname: Malaveille
authors.forename: G
authors.initials: G
authors.lastname: Matullo
authors.forename: A
authors.initials: A
authors.lastname: Dunning
authors.forename: M
authors.initials: M
authors.lastname: Peluso
authors.forename: L
authors.initials: L
authors.lastname: Airoldi
authors.forename: K
authors.initials: K
authors.lastname: Overvad
authors.forename: O
authors.initials: O
authors.lastname: Raaschou-Nielsen
authors.forename: F
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: J P
authors.initials: JP
authors.lastname: Linseisen
authors.forename: R
authors.initials: R
authors.lastname: Kaaks
authors.forename: H
authors.initials: H
authors.lastname: Boeing
authors.forename: A
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: D
authors.initials: D
authors.lastname: Palli
authors.forename: P
authors.initials: P
authors.lastname: Crosignani
authors.forename: R
authors.initials: R
authors.lastname: Tumino
authors.forename: S
authors.initials: S
authors.lastname: Panico
authors.forename: H B
authors.initials: HB
authors.lastname: Bueno-De-Mesquita
authors.forename: P H
authors.initials: PH
authors.lastname: Peeters
authors.forename: E
authors.initials: E
authors.lastname: Lund
authors.forename: C A
authors.initials: CA
authors.lastname: Gonzalez
authors.forename: C
authors.initials: C
authors.lastname: Martinez
authors.forename: M
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: A
authors.initials: A
authors.lastname: Barricarte
authors.forename: C
authors.initials: C
authors.lastname: Navarro
authors.forename: J R
authors.initials: JR
authors.lastname: Quiros
authors.forename: G
authors.initials: G
authors.lastname: Berglund
authors.forename: B
authors.initials: B
authors.lastname: Jarvholm
authors.forename: N E
authors.initials: NE
authors.lastname: Day
authors.forename: T J
authors.initials: TJ
authors.lastname: Key
authors.forename: R
authors.initials: R
authors.lastname: Saracci
authors.forename: E
authors.initials: E
authors.lastname: Riboli
authors.forename: H
authors.initials: H
authors.lastname: Autrup
mesh_terms: 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*
chemical_list: 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