title: Genetic polymorphisms of MPO, GSTT1, GSTM1, GSTP1, EPHX1 and NQO1 as risk factors of early-onset lung cancer.
abstract: Early-onset lung cancer diagnosed up to the age of 50 is a very rare disease, with an increasing incidence rate. Differences in aetiology, characteristics and epidemiology of early and older onset lung cancer have been described previously, suggesting the importance of genetic factors in early-onset lung cancer aetiology. A case-control study was conducted to investigate the effects of genetic polymorphisms in the MPO, EPHX1, GSTT1, GSTM1, GSTP1 and NQO1 genes on the risk of early-onset lung cancer development. Six hundred thirty-eight Caucasian patients under the age of 51 with confirmed primary lung cancer and 1,300 cancer free control individuals, matched by age and sex, were included in this analysis. Seventeen single nucleotide polymorphisms and two deletion polymorphisms were genotyped. No significant association was found for any of the analyzed polymorphisms and overall lung cancer risk. Nonsignificantly decreased risk of lung cancer was observed for carriers of 1 or 2 copies of GSTM1. Subgroup analysis revealed gender- and/or smoking-specific effects of EPHX1 rs2854455 (IV-1464C > T) and rs2234922 (His139Arg), GSTT1 deletion, GSTP1 rs1695 (Ile105Val), rs947895 (+991C > A) and rs4891 (Ser185Ser) and NQO1 rs1800566 (Pro187Ser) polymorphisms. However, none of the observed effects were confirmed by interaction tests nor were they significant after Bonferroni correction for multiple testing. In summary, our study suggested a modifying effect of polymorphisms in EPHX1, GSTP1, GSTT1, GSTM1 and NQO1 genes on the risk of early-onset lung cancer. To confirm these observations and to eliminate possible bias in our analyses, larger studies are warranted.
authors.affiliation: Department of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Timofeeva
authors.forename: Silke
authors.initials: S
authors.lastname: Kropp
authors.forename: Wiebke
authors.initials: W
authors.lastname: Sauter
authors.forename: Lars
authors.initials: L
authors.lastname: Beckmann
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Birgit
authors.initials: B
authors.lastname: Jäger
authors.forename: Kirstin
authors.initials: K
authors.lastname: Mittelstrass
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Helmut
authors.initials: H
authors.lastname: Bartsch
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeböller
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.forename: Heinz-Erich
authors.initials: HE
authors.lastname: Wichmann
mesh_terms: D017668:Age of Onset; D002353:Carrier State; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D017384:Sequence Deletion; D012907:Smoking / Q000235:genetics
chemical_list: D009195:Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D051549:Glutathione S-Transferase pi