The study also receives support selleck chemicals from the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London. TDS is an NIHR senior Investigator. The project also received support from a Biotechnology and biological Sciences Research Council (BBSRC) project grant. Vis: The Vis study (Croatia) was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (Contract No. LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy.
Batimastat Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer. British Journal of Cancer (2002) 21, 630�C634. doi:10.1038/sj.bjc.6600511 www.bjcancer.com ? 2002 Cancer Research UK Keywords: colorectal cancer, TGF��, signalling, SMAD, predictive marker Deletion of the chromosomal region 18q21 is the most frequent cytogenetic alteration observed in colorectal cancer (CRC), suggesting the location of a tumour suppressor locus in this region (Vogelstein et al, 1988; Mitelman et al, 1997).