Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU)-containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real-time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome.
- MeSH
- ABC transportéry genetika MeSH
- adjuvantní chemoterapie MeSH
- antitumorózní látky terapeutické užití MeSH
- kolon metabolismus MeSH
- kolorektální nádory farmakoterapie genetika mortalita MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- metastázy nádorů MeSH
- míra přežití MeSH
- pilotní projekty MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prognóza MeSH
- progrese nemoci MeSH
- regulace genové exprese u nádorů MeSH
- rektum metabolismus MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: Ornithine decarboxylase (ODC) is a modifier of adenomatous polyposis coli-dependent tumourigenesis. The G316 > A polymorphism in intron 1 of the ODC gene lies between two myc-binding domains and alters the expression of the gene to affect polyamine metabolism. This variant may be associated with recurrence of colorectal adenoma. We examined whether this variant also modified the susceptibility to sporadic colorectal cancer (CRC). METHOD: The G316 > A variant was analysed in a large (n = 754) CRC case-controlled series of hospital patient volunteers (n = 627) in the Czech Republic, and the relationship with cancer risk was estimated by conditional logistic regression. RESULTS: After adjusting for age and sex, G316 > A was associated with no decrease in CRC risk for either heterozygotes [odds ratio 0.98, 95% confidence interval (CI) 0.77-1.23] or rare allele homozygotes (odds ratio 0.92, 95% CI 0.61-1.37). CONCLUSION: The G316 > A functional variant in the ODC gene is unlikely to make much impact on reducing CRC risk regardless of the reduction in risk found for the recurrence of colorectal adenoma.
- MeSH
- dospělí MeSH
- genotyp MeSH
- introny MeSH
- jednonukleotidový polymorfismus * MeSH
- karcinom genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- nádory rekta genetika MeSH
- nádory tračníku genetika MeSH
- ornithindekarboxylasa genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
