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Analysis of candidate genes for the susceptibility to lung cancer in patients under 50 years old

Objective

There is much interest on whether some individuals are more genetically susceptible than others to developing lung cancer. Genetic polymorphisms in genes involved in the metabolism of tobacco, DNA repair, cell cycle control, and nicotine addiction are ca ndidate to determine such a susceptibility. A tool to study the genetic susceptibility is to carry out case-control association studies with a high quality information on lifestyle and to have high-throughput technologies for genotyping a broad selection of genes. During the MCF fellowship period, we set up an oligonucleotide micro-array based on arrayed primer extension technology (APEX) that allows the parallel high-throughput genotyping of 158 single nucleotide polymorphisms in 51 candidate genes. T he genes are reported as follows: ADH1B, ALDH2, APE1, CDKN2A, COMT, CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C19, CYP2C9, CYP2D6, CYP2E1, CYP3A4, DRD2, DRD4, EPHX1, ERCC1, ERCC2, ERCC4, ERCC5, GRPR, GSTA2, GSTA4, GSTM1, GSTM3, GSTP1, GSTT2, LIG3, MDM2, MGMT, MnSOD2, MPO, MPC, MTHFR, NATI, NAT2, NQO1, OGGI, CDKN1A, PCNA, POLB, SLC6A3, SULT1A1, TP53, TPMT, UGT1A7, XRCC1, XRCC2, XRCC3, XRCC9. We called this microarray \"MetaboChip\" and we have already validated it by genotyping a standard reference sample se t (SNP500 from NCI). Now, we are aiming to use MetaboChip to genotype a cohort of DNA samples (310 patients, 310 controls) who are part of a larger multicentric case-control study. To better investigate the role of genetics, we will focus on patients who developed the disease before the age of 50 years. Most of the polymorphisms included in MetaboChip are demonstrated to have a biological significance and the study will allow testing hypothesis of the interaction between tobacco-smoke and genotypes (hyp othesis testing). Moreover, part of the SNPs will be just explored, as there is not information about their functional role.

Call for proposal

FP6-2002-MOBILITY-11
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Coordinator

UNIVERSITA DEGLI STUDI DI PISA
Address
Lungarno Pacinotti 43-44
Pisa
Italy

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