Researchers from Basel, Switzerland, evaluated how the gene SMAD4 affects patients with colorectal cancer and their response to 5-fluorouracil-based chemotherapy.
SMAD4 is the gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signaling.
It is a potential suppressor of colorectal carcinogenesis, and is located at the chromosomal region 18q21.
The clinical relevance of SMAD4 deletion was evaluated.
Gene copy alterations were determined by copy dosage, using real-time quantitative PCR.
| Normal SMAD4 diploidy increased the benefit of chemotherapy by 3-fold.
| British Journal of Cancer |
This was done in 202 colorectal tumor biopsies from a previous randomized study of adjuvant chemotherapy.
Patients with normal SMAD4 diploidy turned out to have a 3-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy, with a border line significance (overall survival: 3.23; disease-free survival: 2.89).
The authors note that 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.
Jean-Louis Boulay, of the University Hospital, Basel, said on behalf of his colleagues, "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 may be a critical factor for benefit of chemotherapy in patients with colorectal cancer," he concluded.