title: Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene.
abstract: The polymorphism SNP309 (rs2279744) in the promoter region of the MDM2 gene has been shown to alter protein expression and may play a role in the susceptibility to lung cancer. The MDM2 protein is a key inhibitor of p53 and several mechanisms of MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth and apoptosis.We used 635 Caucasian patients diagnosed with lung cancer before 51 years of age and 1300 healthy gender and age frequency matched population Caucasian controls to investigate the association between the MDM2 SNP309 and the risk of developing early onset lung cancer. Conditional logistic models were applied to assess the genotype-phenotype association, adjusted for smoking. Compared to the GG genotype, the adjusted ORs for the TG and TT genotype were 0.9 (95% CI: 0.7-1.5) and 1.0 (95% CI: 0.7-1.5), respectively. Also no association was found for histological subtypes of lung cancer. The strength of this study is that within young cases the genetic component to develop lung cancer may be greater. Our results indicate that the MDM2 SNP309 is not significantly associated with lung carcinogenesis but point towards gender-specific differences.
authors.affiliation: Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Epidemiology, Munich/Neuherberg, Germany. kirstin.mittelstrass@helmholtz-muenchen.de
authors.forename: Kirstin
authors.initials: K
authors.lastname: Mittelstrass
authors.forename: Wiebke
authors.initials: W
authors.lastname: Sauter
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Maria
authors.initials: M
authors.lastname: Timofeeva
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sybrecht
authors.forename: Gabi
authors.initials: G
authors.lastname: Woelke
authors.forename: Mathias
authors.initials: M
authors.lastname: Cebulla
authors.forename: Maria
authors.initials: M
authors.lastname: Degen
authors.forename: Harald
authors.initials: H
authors.lastname: Morr
authors.forename: Peter
authors.initials: P
authors.lastname: Drings
authors.forename: Andreas
authors.initials: A
authors.lastname: Groeschel
authors.forename: Karsten Grosse
authors.initials: KG
authors.lastname: Kreymborg
authors.forename: Karl
authors.initials: K
authors.lastname: Haeussinger
authors.forename: Gerd
authors.initials: G
authors.lastname: Hoeffken
authors.forename: Christine
authors.initials: C
authors.lastname: Schmidt
authors.forename: Bettina
authors.initials: B
authors.lastname: Jilge
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schmidt
authors.forename: You-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Dagmar
authors.initials: D
authors.lastname: Taeuscher
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Heinz-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeboeller
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015984:Causality; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2