Skip to main content
Erschienen in: Cellular Oncology 4/2011

01.08.2011 | Original Paper

TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients

verfasst von: A. Fariña-Sarasqueta, M. J. E. M. Gosens, E. Moerland, I. van Lijnschoten, V. E. P. P. Lemmens, G. D. Slooter, H. J. T. Rutten, Adriaan J. C. van den Brule

Erschienen in: Cellular Oncology | Ausgabe 4/2011

Einloggen, um Zugang zu erhalten

Abstract

Aim

Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.

Patients and methods

251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5′untranslated region of the TS gene were genotyped.

Results

There was a positive association between tumor T stage and the VNTR genotypes (p = 0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes.

Conclusion

We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.
Literatur
1.
Zurück zum Zitat D.B. Longley, D.P. Harkin, P.G. Johnston, 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5), 330–338 (2003)PubMedCrossRef D.B. Longley, D.P. Harkin, P.G. Johnston, 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5), 330–338 (2003)PubMedCrossRef
2.
Zurück zum Zitat G.J. Peters et al., Induction of thymidylate synthase as 5-fluorouracil resistance mechanism. Biochim Biophys Acta 1587, 194–205 (2002)PubMed G.J. Peters et al., Induction of thymidylate synthase as 5-fluorouracil resistance mechanism. Biochim Biophys Acta 1587, 194–205 (2002)PubMed
3.
Zurück zum Zitat O. Belvedere et al., Lack of correlation between immunohistochemical expression of E2F-1, thymidylate synthase expression and clinical response to 5-fluorouracil in advanced colorectal cancer. Ann Oncol 15, 55–58 (2004)PubMedCrossRef O. Belvedere et al., Lack of correlation between immunohistochemical expression of E2F-1, thymidylate synthase expression and clinical response to 5-fluorouracil in advanced colorectal cancer. Ann Oncol 15, 55–58 (2004)PubMedCrossRef
4.
Zurück zum Zitat M. Ciaparrone et al., Predictive role of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer patients receiving adjuvant 5-fluorouracil. Oncology 70, 366–377 (2006)PubMedCrossRef M. Ciaparrone et al., Predictive role of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer patients receiving adjuvant 5-fluorouracil. Oncology 70, 366–377 (2006)PubMedCrossRef
5.
Zurück zum Zitat D. Edler et al., Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer. Clin Cancer Res 6, 1378–1384 (2000)PubMed D. Edler et al., Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer. Clin Cancer Res 6, 1378–1384 (2000)PubMed
6.
Zurück zum Zitat M.E. Fernandez-Contreras et al., Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil. Int J Oncol 28(5), 1303–1310 (2006)PubMed M.E. Fernandez-Contreras et al., Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil. Int J Oncol 28(5), 1303–1310 (2006)PubMed
7.
Zurück zum Zitat S.A. Jensen, B. Vainer, J.B. Sørensen, The prognostic significance of thymidylate synthase and dihydropyrimidine dehydrogenase in colorectal cancer of 303 patients adjuvantly treated with 5- Fluorouracil. Int J Cancer 120, 694–701 (2006)CrossRef S.A. Jensen, B. Vainer, J.B. Sørensen, The prognostic significance of thymidylate synthase and dihydropyrimidine dehydrogenase in colorectal cancer of 303 patients adjuvantly treated with 5- Fluorouracil. Int J Cancer 120, 694–701 (2006)CrossRef
8.
Zurück zum Zitat M. Kornmann et al., Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5- fluorouracil. Clin Cancer Res 9, 4116–4124 (2003)PubMed M. Kornmann et al., Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5- fluorouracil. Clin Cancer Res 9, 4116–4124 (2003)PubMed
9.
Zurück zum Zitat H.-J. Lenz et al., p53 and thymidylate synthase expression in untreated stage II colon cancer: associations with recurrence, survival, and site. Clin Cancer Res 4, 1227–1234 (1998)PubMed H.-J. Lenz et al., p53 and thymidylate synthase expression in untreated stage II colon cancer: associations with recurrence, survival, and site. Clin Cancer Res 4, 1227–1234 (1998)PubMed
10.
Zurück zum Zitat S. Popat, R. Wort, R.S. Houlston, Inter-relationship between microsatellite instability, thymidylate synthase expression, and p53 status in colorectal cancer: implications for chemoresistance. BMC Cancer 6, 150–158 (2006)PubMedCrossRef S. Popat, R. Wort, R.S. Houlston, Inter-relationship between microsatellite instability, thymidylate synthase expression, and p53 status in colorectal cancer: implications for chemoresistance. BMC Cancer 6, 150–158 (2006)PubMedCrossRef
11.
Zurück zum Zitat K. Uchida et al., Loss of heterozygosity at the thymidyalte synthase (TS) locus on chromosome 18 affects tumor response and survival in individuals heterozygous for a 28-bp polymorphism in the TS gene. Clin Cancer Res 10, 433–439 (2004)PubMedCrossRef K. Uchida et al., Loss of heterozygosity at the thymidyalte synthase (TS) locus on chromosome 18 affects tumor response and survival in individuals heterozygous for a 28-bp polymorphism in the TS gene. Clin Cancer Res 10, 433–439 (2004)PubMedCrossRef
12.
Zurück zum Zitat J.L. Westra et al., Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients. Ann Oncol 16, 1646–1653 (2005)PubMedCrossRef J.L. Westra et al., Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients. Ann Oncol 16, 1646–1653 (2005)PubMedCrossRef
13.
Zurück zum Zitat F. Amatori et al., Thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer and normal mucosa in patients. Pharmacogenet Genomics 16, 809–816 (2006)PubMedCrossRef F. Amatori et al., Thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer and normal mucosa in patients. Pharmacogenet Genomics 16, 809–816 (2006)PubMedCrossRef
14.
Zurück zum Zitat A. Artinyan et al., Molecular predictors of lymph node metastasis in colon cancer: increased risk with decreased thymidylate synthase expression. J Gastroint Surg 9, 1216–1221 (2005)CrossRef A. Artinyan et al., Molecular predictors of lymph node metastasis in colon cancer: increased risk with decreased thymidylate synthase expression. J Gastroint Surg 9, 1216–1221 (2005)CrossRef
15.
Zurück zum Zitat W. Ichikawa et al., Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastaric colorectal cancer. Clin Cancer Res 9, 786–791 (2003)PubMed W. Ichikawa et al., Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastaric colorectal cancer. Clin Cancer Res 9, 786–791 (2003)PubMed
16.
Zurück zum Zitat T. Liersch et al., Lymph node status and TS gene expression are prognostic markers in stage II/III rectal cancer after neoadjuvant fluorouracil-based chemoradiotherapy. J Clin Oncol 24(25), 4062–4068 (2006)PubMedCrossRef T. Liersch et al., Lymph node status and TS gene expression are prognostic markers in stage II/III rectal cancer after neoadjuvant fluorouracil-based chemoradiotherapy. J Clin Oncol 24(25), 4062–4068 (2006)PubMedCrossRef
17.
Zurück zum Zitat N.J. Meropol et al., Thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer. J Clin Oncol 24(25), 4069–4077 (2006)PubMedCrossRef N.J. Meropol et al., Thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer. J Clin Oncol 24(25), 4069–4077 (2006)PubMedCrossRef
18.
Zurück zum Zitat D. Salonga et al., Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase and thymidine phosphorylase. Clin Cancer Res 6, 1322–1327 (2000)PubMed D. Salonga et al., Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase and thymidine phosphorylase. Clin Cancer Res 6, 1322–1327 (2000)PubMed
19.
Zurück zum Zitat Y. Shirota et al., ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 19(23), 4298–4304 (2001)PubMed Y. Shirota et al., ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 19(23), 4298–4304 (2001)PubMed
20.
Zurück zum Zitat D. Vallböhmer et al., Molecular factors of 5-fluorouracil metabolism in colorectal cancer: Analysis of primary tumor and lymph node metastasis. Int J Oncol 28, 527–533 (2006)PubMed D. Vallböhmer et al., Molecular factors of 5-fluorouracil metabolism in colorectal cancer: Analysis of primary tumor and lymph node metastasis. Int J Oncol 28, 527–533 (2006)PubMed
21.
Zurück zum Zitat Xi, Y., et al., Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics, 2006. 7. Xi, Y., et al., Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics, 2006. 7.
22.
Zurück zum Zitat Y. Yanagisawa et al., Modified irinotecan/5-FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes. Scan J Gastroenterol 42, 477–484 (2007)CrossRef Y. Yanagisawa et al., Modified irinotecan/5-FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes. Scan J Gastroenterol 42, 477–484 (2007)CrossRef
23.
Zurück zum Zitat J. Chen et al., Polymorphism in the thymidylate synthase promoter enhancer region modifies the risk and survival of colorectal cancer. Cancer Epidemiol, Biomarkers Prevent 12, 958–962 (2003) J. Chen et al., Polymorphism in the thymidylate synthase promoter enhancer region modifies the risk and survival of colorectal cancer. Cancer Epidemiol, Biomarkers Prevent 12, 958–962 (2003)
24.
Zurück zum Zitat H.-J. Cho et al., Thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) polymorphisms in the Korean population for prediction of 5-fluorouracil associated toxicity. Therap Drug Monitor 29(2), 190–196 (2007)CrossRef H.-J. Cho et al., Thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) polymorphisms in the Korean population for prediction of 5-fluorouracil associated toxicity. Therap Drug Monitor 29(2), 190–196 (2007)CrossRef
25.
Zurück zum Zitat K. Curtin et al., Thymidylate synthase polymorphisms and colon cancer: Associations with tumor stage, tumor characteristics and survival. Int J Cancer 120, 2226–2232 (2007)PubMedCrossRef K. Curtin et al., Thymidylate synthase polymorphisms and colon cancer: Associations with tumor stage, tumor characteristics and survival. Int J Cancer 120, 2226–2232 (2007)PubMedCrossRef
26.
Zurück zum Zitat E. Hitre et al., Influence of thymidylate synthase gene polymorphisms on the survival of colorectal cancer patients receiving adjuvant 5-fluorouracil. Pharmacogenet Genomics 15, 723–730 (2005)PubMedCrossRef E. Hitre et al., Influence of thymidylate synthase gene polymorphisms on the survival of colorectal cancer patients receiving adjuvant 5-fluorouracil. Pharmacogenet Genomics 15, 723–730 (2005)PubMedCrossRef
27.
Zurück zum Zitat B. Iacopetta et al., A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. Br J Cancer 85(6), 827–830 (2001)PubMedCrossRef B. Iacopetta et al., A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. Br J Cancer 85(6), 827–830 (2001)PubMedCrossRef
28.
Zurück zum Zitat A. Jakobsen et al., Thymidylate synthase and Methyltetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. J Clin Oncol 23(7), 1365–1369 (2005)PubMedCrossRef A. Jakobsen et al., Thymidylate synthase and Methyltetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. J Clin Oncol 23(7), 1365–1369 (2005)PubMedCrossRef
29.
Zurück zum Zitat K. Kawakami et al., Functional polymorphism of the thymidylate synthase gene in colorectal cancer accompanied by frequent loss of heterozygosity. Jap J Cancer Res 93, 1221–1229 (2002) K. Kawakami et al., Functional polymorphism of the thymidylate synthase gene in colorectal cancer accompanied by frequent loss of heterozygosity. Jap J Cancer Res 93, 1221–1229 (2002)
30.
Zurück zum Zitat K. Kawakami et al., Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression. Clin Cancer Res 7, 4096–4101 (2001)PubMed K. Kawakami et al., Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression. Clin Cancer Res 7, 4096–4101 (2001)PubMed
31.
Zurück zum Zitat K. Kawakami, Y. Watanabe, Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res 63, 6004–6007 (2003)PubMed K. Kawakami, Y. Watanabe, Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res 63, 6004–6007 (2003)PubMed
32.
Zurück zum Zitat T. Lecomte et al., Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. Clin Cancer Res 10, 5880–5888 (2004)PubMedCrossRef T. Lecomte et al., Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. Clin Cancer Res 10, 5880–5888 (2004)PubMedCrossRef
33.
Zurück zum Zitat E. Marcuello et al., Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. Int J Cancer 112, 733–737 (2004)PubMedCrossRef E. Marcuello et al., Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. Int J Cancer 112, 733–737 (2004)PubMedCrossRef
34.
Zurück zum Zitat S.T. Pullarkat et al., Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 1, 65–70 (2001)PubMedCrossRef S.T. Pullarkat et al., Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 1, 65–70 (2001)PubMedCrossRef
35.
Zurück zum Zitat A. Ruzzo et al., Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol 25(10), 1247–1254 (2007)PubMedCrossRef A. Ruzzo et al., Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol 25(10), 1247–1254 (2007)PubMedCrossRef
36.
Zurück zum Zitat J. Stoehlmacher et al., A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 91, 344–354 (2004)PubMed J. Stoehlmacher et al., A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 91, 344–354 (2004)PubMed
37.
Zurück zum Zitat K.W. Suh et al., Thymidylate synthase gene polymorphism as a prognostic factor for colon cancer. J Gastrointest Surg 9(3), 336–342 (2005)PubMedCrossRef K.W. Suh et al., Thymidylate synthase gene polymorphism as a prognostic factor for colon cancer. J Gastrointest Surg 9(3), 336–342 (2005)PubMedCrossRef
38.
Zurück zum Zitat T. Tsuji et al., Polymorphism in the thymidylate synthase promoter enhancer region is not an efficacious maker for tumor sensitivity to 5-fluorouracil-based oral adjuvant chemotherapy in colorectal cancer. Clin Cancer Res 9, 3700–3704 (2003)PubMed T. Tsuji et al., Polymorphism in the thymidylate synthase promoter enhancer region is not an efficacious maker for tumor sensitivity to 5-fluorouracil-based oral adjuvant chemotherapy in colorectal cancer. Clin Cancer Res 9, 3700–3704 (2003)PubMed
39.
Zurück zum Zitat E. Villafranca et al., Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 19(6), 1779–1786 (2001)PubMed E. Villafranca et al., Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 19(6), 1779–1786 (2001)PubMed
40.
Zurück zum Zitat S. Popat, A. Matakidoue, R.S. Houlston, Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 22(3), 529–536 (2004)PubMedCrossRef S. Popat, A. Matakidoue, R.S. Houlston, Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 22(3), 529–536 (2004)PubMedCrossRef
41.
Zurück zum Zitat M.J. Gosens et al., Thymidylate synthase genotyping is more predictive for therapy response than immunohistochemistry in patients with colon cancer. Int J Cancer 123(8), 1941–1949 (2008)PubMedCrossRef M.J. Gosens et al., Thymidylate synthase genotyping is more predictive for therapy response than immunohistochemistry in patients with colon cancer. Int J Cancer 123(8), 1941–1949 (2008)PubMedCrossRef
42.
Zurück zum Zitat K. Kawakami et al., Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res 19, 3249–3252 (1999)PubMed K. Kawakami et al., Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res 19, 3249–3252 (1999)PubMed
43.
Zurück zum Zitat M.V. Mandola et al., A novel single nucleotide polymorphism within 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res 63, 3898–2904 (2003) M.V. Mandola et al., A novel single nucleotide polymorphism within 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res 63, 3898–2904 (2003)
44.
Zurück zum Zitat F. Prall et al., Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma? Oncol Rep 18(1), 203–209 (2007)PubMed F. Prall et al., Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma? Oncol Rep 18(1), 203–209 (2007)PubMed
45.
Zurück zum Zitat G. Lurje et al., Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer. Pharmacogenet Genomics 18(2), 161–168 (2008)PubMedCrossRef G. Lurje et al., Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer. Pharmacogenet Genomics 18(2), 161–168 (2008)PubMedCrossRef
46.
Zurück zum Zitat M. Frattini et al., Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res 10(12 Pt 1), 4015–4021 (2004)PubMedCrossRef M. Frattini et al., Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res 10(12 Pt 1), 4015–4021 (2004)PubMedCrossRef
47.
Zurück zum Zitat E. Giovannetti et al., Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels. Br J Cancer 96, 769–775 (2007)PubMedCrossRef E. Giovannetti et al., Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels. Br J Cancer 96, 769–775 (2007)PubMedCrossRef
48.
Zurück zum Zitat E. Odin et al., Colorectal carcinomas with microsatellite instability display increased thymidylate synthase gene expression levels. Clin Colorectal Cancer 6(10), 720–727 (2007)PubMedCrossRef E. Odin et al., Colorectal carcinomas with microsatellite instability display increased thymidylate synthase gene expression levels. Clin Colorectal Cancer 6(10), 720–727 (2007)PubMedCrossRef
49.
Zurück zum Zitat R.A. Hubner et al., Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma. Br J Cancer 97(10), 1449–1456 (2007)PubMedCrossRef R.A. Hubner et al., Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma. Br J Cancer 97(10), 1449–1456 (2007)PubMedCrossRef
50.
Zurück zum Zitat M.F. de Maat et al., Assessment of methylation events during colorectal tumor progression by absolute quantitative analysis of methylated alleles. Mol Cancer Res 5(5), 461–471 (2007)PubMedCrossRef M.F. de Maat et al., Assessment of methylation events during colorectal tumor progression by absolute quantitative analysis of methylated alleles. Mol Cancer Res 5(5), 461–471 (2007)PubMedCrossRef
51.
Zurück zum Zitat H. Nakagawa et al., Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res 61(19), 6991–6995 (2001)PubMed H. Nakagawa et al., Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res 61(19), 6991–6995 (2001)PubMed
52.
Zurück zum Zitat M. Li et al., Proteomic analysis of the aging-related proteins in human normal colon epithelial tissue. J Biochem Mol Biol 40(1), 72–81 (2007)PubMedCrossRef M. Li et al., Proteomic analysis of the aging-related proteins in human normal colon epithelial tissue. J Biochem Mol Biol 40(1), 72–81 (2007)PubMedCrossRef
53.
Zurück zum Zitat M. Morris, C. Platell, B. Iacopetta, A population-based study of age-related variation in clinicopathological features, molecular. Markers and outcome from colorectal cancer. Anticancer Res 27(4C), 2833–2838 (2007)PubMed M. Morris, C. Platell, B. Iacopetta, A population-based study of age-related variation in clinicopathological features, molecular. Markers and outcome from colorectal cancer. Anticancer Res 27(4C), 2833–2838 (2007)PubMed
Metadaten
Titel
TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients
verfasst von
A. Fariña-Sarasqueta
M. J. E. M. Gosens
E. Moerland
I. van Lijnschoten
V. E. P. P. Lemmens
G. D. Slooter
H. J. T. Rutten
Adriaan J. C. van den Brule
Publikationsdatum
01.08.2011
Verlag
Springer Netherlands
Erschienen in
Cellular Oncology / Ausgabe 4/2011
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-011-0030-z

Weitere Artikel der Ausgabe 4/2011

Cellular Oncology 4/2011 Zur Ausgabe

Neu im Fachgebiet Pathologie