The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Polymorphisms of the Repeated Sequences in the Enhancer Region of the Thymidylate Synthase Gene Promoter May Predict Downstaging After Preoperative Chemoradiation in Rectal Cancer
Abstract
PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)–based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU–based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P = .036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P = .17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU–based chemoradiation.
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Cites
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Cited by
Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism
Peters, G. J., Backus, H. H. J., Freemantle, S., van Triest, B., Codacci-Pisanelli, G., van der Wilt, C. L., Smid, K., Lunec, J., Calvert, A. H., Marsh, S., et al. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(02)00082-0 · Cited by 420
Polymorphisms affecting gene regulation and mRNA processing: Broad implications for pharmacogenetics
JOHNSON, A., WANG, D., & SADEE, W. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.11.001 · Cited by 97
Metadata
- Authors
- Villafranca, E., Okruzhnov, Y., Dominguez, M. A., García-Foncillas, J., Azinovic, I., Martínez, E., Illarramendi, J. J., Arias, F., Martínez-Monge, R., Salgado, E., Angeletti, S., & Brugarolas, A.
- Venue
- Journal of Clinical Oncology
- Published
- 2001-03-15
- Volume
- 19
- Issue
- 6
- Pages
- 1779-1786
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2200882253
- Cited by
- 308
- References
- 25
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- closed
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- Villafranca, E., Okruzhnov, Y., Dominguez, M. A., García-Foncillas, J., Azinovic, I., Martínez, E., Illarramendi, J. J., Arias, F., Martínez-Monge, R., Salgado, E., Angeletti, S., & Brugarolas, A. (2001). Polymorphisms of the Repeated Sequences in the Enhancer Region of the Thymidylate Synthase Gene Promoter May Predict Downstaging After Preoperative Chemoradiation in Rectal Cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2001.19.6.1779
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