Artikel
Collaborative case-control study of genetic susceptibility in early onset lung cancer
Suche in Medline nach
Autoren
Veröffentlicht: | 6. September 2007 |
---|
Gliederung
Text
Background: Lung cancer (LC) is a frequent malignant tumor. A combination of smoking and genetic susceptibility leads to LC especially within early onset of disease. The analysis of candidate genes especially in young patients is fundamental for the investigation of genetic epidemiology in this group.
Material and Methods: For each case about two age and sex matched controls were included. 635 young cases (age below 50) have been recruited by the GSF in collaboration with the University of Göttingen (LUCY Study) and by the DKFZ-collaboration with the Thoraxklinik Heidelberg. The controls (n=1300) stem from the population based KORA study (GSF).
Genotyping of SNPs was performed by MALDI TOF MS (matrix assisted laser desorption ionisation time of flight mass spectrometry) and fluorescence-based melting curve analyses (LightCycler). A method for semiquantitative deletion genotyping is being developed.
Results: Genotyping was successful for 80 single nucleotide polymorphisms (SNPs) in candidate genes coding for metabolizing enzymes (CYP1A1, CYP1B1, CYP2A13, CYP3A4, CYP3A5, MPO, GSTM1, GSTP1, GSTT, EPHX1, SULT1A1 and NQO1) and in genes coding for DNA repair proteins (XRCC1, hOGG1, ERCC2, XRCC3, NBS1 and RAD50). Additionally four more candidate genes of other pathways were genotyped (MTHFR, MMP1, MDM2 and PDCD5). Statistical analyses are still in process and first results will be presented.
Conclusions: For replication several study populations are available. From the same area as the cases, families of young LC patients are available. In the International Lung Cancer COnsortium (ILCCO) about 1500 LC under 50 and controls are available. Furthermore significant associations will be tested for their impact in older LC patients. For this aim cases and controls of older LC patients from the GSF and from the DKFZ-Thoraxklinik collaboration in Heidelberg are on hand.