FP6Реинтеграция2004–2005

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

6РП — Действия „Мария Кюри“

Период: 2004-04-01 → 2005-03-31
Финансиране от ЕС: 40 000 €
Участници: 1
Схема: ERG

Линиите свързват координатора с партньорите.

Накратко на български

Генетичните вариации в гените за метаболизъм, възпаление и ремонт на ДНК се анализират при пациенти с рак на белия дроб под 50 години. Това помага да се разбере как наследствената предразположеност и външни фактори, като цигаретния дим, влияят върху развитието на болестта.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Final Activity Report Summary - LUNG CANCER UNDER 50 (Analysis of candidate genes for the susceptibility to lung cancer in patients under 50 years old)

During the two year Marie Curie (MC) fellowship and the one year European reintegration grant (ERG) I learned: 1. how to make microarrays for genotyping human deoxyribonucleic acid (DNA) samples 2. how to perform case-control association studies. We studied the role of various genetic polymorphisms, in genes of xenobiotic metabolism, DNA repair and inflammation, in relation to gastroenterological and pulmonary cancers. We found that polymorphisms within inflammatory genes, e.g. IL6, affected the risk of colorectal cancer, whereas an interesting association between DNA repair genes and lung cancer in early-onset lung cancers was also observed. Moreover, several genetic risk factors were found among xenobiotic metabolism and lung cancer. The data pointed and stressed towards the role of inflammation for the colorectal cancer, whereas metabolism of xenobiotics, likely due to the inhaled cigarette smoke, and DNA repair played an important role in early-onset lung cancer. Finally, we studied the role of genetic variants within TP53 and found that Arg72Pro and, to a greater extent, a duplication of 16bp within the intron 3 of TP53, were related to lung and colorectal cancers, stressing further that genetic susceptibility could be related to genetic variations within p53.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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."

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA DEGLI STUDI DI PISA · PISAКоординаторИталия

Връзки

Виж в CORDIS