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Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers
Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The TS gene promoter enhancer region contains two different polymorphisms which can influence TS mRNA transcriptional and trans...
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Published in: | European journal of cancer (1990) 2005-09, Vol.41 (14), p.2176-2183 |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The
TS gene promoter enhancer region contains two different polymorphisms which can influence
TS mRNA transcriptional and translational efficiency: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism (SNP), G
>
C, within the second repeat of the 3R alleles. We studied the relationship between tumoural
TS mRNA expression levels and
TS gene polymorphisms in the colonic mucosa of 48 colorectal cancer patients. The 3R/3R genotype was characterised by higher
TS mRNA levels in the tumour than the 2R/2R–2R/3R genotypes (
P
=
0.071). Regarding the relationship with the SNP polymorphism, a statistically significant difference in
TS gene expression between the 3RG/3RG genotype and 2R/2R–2R/3RC–2R/3RG genotype subset was observed (
P
=
0.017). No statistically significant correlation was observed between experimental data and baseline clinical-pathological characteristics as well as clinical outcome in the relatively small patient series investigated. This is the first study reporting an association between the
TS intra-repeat SNP and gene expression levels in colorectal cancer patients. These results suggest that in 3R/3R patients, the G
>
C polymorphism may be an important factor in determining
TS mRNA expression levels, and warrant further investigation of the role of
TS promoter polymorphisms as predictors of sensitivity to 5-FU-based chemotherapy in larger case series. |
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ISSN: | 0959-8049 1879-0852 |
DOI: | 10.1016/j.ejca.2005.06.016 |