Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients with metastatic colorectal cancer: A sensitivity marker to 5-FU-based therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14532-14532
Author(s):  
O. O. Castillo Fernandez ◽  
L. A. Herrera ◽  
C. Castro ◽  
G. Calderillo ◽  
R. Herrera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
C677t Polymorphism ◽  
Standard Chemotherapy ◽  
C677t Mthfr ◽  
Mthfr Gene Polymorphism

14532 Background: 5-Fluorouracil (5FU) and Folinic Acid (FA) with either oxaliplatin or irinotecan have become the standard chemotherapy used for metastatic colorectal cancer. However, more than 50% of our patients cannot afford it. Moreover, we lack of predictive markers to 5FU/AF therapy. The methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the folate pool and its substrate 5,10-methylenetetrahydrofolate is needed for modulation of 5FU. The C677T MTHFR gene polymorphism is highly prevalent in Mexican population and is linked to altered enzyme activity and increases substrate levels. Many studies have suggested a better response rate to fluoropyrimidine based therapy related with C677T polymorphism. The aim of this study was to evaluate the presence of this polymorphism and its relation with progression free and overall survival in metastatic colon cancer treated with 5FU/FA Methods: Sections of paraffin- embedded healthy colonic mucosa of 29 patients with metastatic unresectable colorectal cancer treated with 5FU/FA as first line chemotherapy between 1998 and 2004 were collected to obtain DNA and determine the polymorphism by PCR and allele specific digestion. Results: We found a highly proportion of at least one mutated allele in our patients (8 homozygous wild type CC, 15 heterozygous CT, 6 mutated homozygous TT). C677T MTHFR gene polymorphism showed statistically significant differences in median progression free survival non polymorphic CC 3.23±0.68 month versus 4.8±0.18 month in polymorphic group CT and TT (p= 0.011 log rank test) and median overall survival in non polymorphic groups 6.7±2.63month versus 13 ±2.51 month in polymorphic group (p= 0.03 Breslow test).No other variable affected progression free or overall survival on univariate analysis. Conclusions: Our findings suggest that C677T polymorphism could play a role on survival in metastatic colorectal cancer treated with 5FU/FA. Futher studies evaluating standard chemotherapy and the analyzed polymorphism are recommended. No significant financial relationships to disclose.

Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity

2005 ◽  
Vol 23 (7) ◽  
pp. 1365-1369 ◽  
Author(s):  
Anders Jakobsen ◽  
Jens Nederby Nielsen ◽  
Niels Gyldenkerne ◽  
Jan Lindeberg
Keyword(s):  
Gene Polymorphism ◽  
Retrospective Analysis ◽  
Thymidylate Synthase ◽  
Methylenetetrahydrofolate Reductase ◽  
Response Rate ◽  
Prospective Trial ◽  
Mthfr Gene ◽  
Mthfr Gene Polymorphism ◽  
The Difference ◽  
Methylenetetrahydrofolate Reductase Gene Polymorphism

Purpose To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity. Patients and Methods The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes. Results The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial. Conclusion The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.

Correlation Between C677T MTHFR Gene Polymorphism, Plasma Homocysteine Levels and the Incidence of CAD

2001 ◽  
Vol 1 (5) ◽  
pp. 353-361 ◽  
Author(s):  
Kenji Nakai ◽  
Chuichi Itoh ◽  
Keiko Nakai ◽  
Wataru Habano ◽  
David Gurwitz
Keyword(s):  
Gene Polymorphism ◽  
Mthfr Gene ◽  
Plasma Homocysteine ◽  
C677t Mthfr ◽  
Mthfr Gene Polymorphism

scholarly journals Effectiveness and Costs Associated to Adding Cetuximab or Bevacizumab to Chemotherapy as Initial Treatment in Metastatic Colorectal Cancer: Results from the Observational FABIO Project

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 839 ◽  
Author(s):  
Matteo Franchi ◽  
Donatella Garau ◽  
Ursula Kirchmayer ◽  
Mirko Di Martino ◽  
Marilena Romero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Time ◽  
Initial Treatment ◽  
Biological Therapy ◽  
Population Based ◽  
Study Cohort ◽  
Standard Chemotherapy ◽  
Kaplan Meier

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan–Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months (p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy.

A Study of the MTHFR Gene Polymorphism C677T in Colorectal Cancer

2009 ◽  
Vol 8 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Kristoffer Derwinger ◽  
Yvonne Wettergren ◽  
Elisabeth Odin ◽  
Göran Carlsson ◽  
Bengt Gustavsson
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Mthfr Gene ◽  
Mthfr Gene Polymorphism

scholarly journals Methylenetetrahydrofolate Reductase Gene Polymorphism (C677T) as a Risk Factor for Arterial Thrombosis in Georgian Patients

2018 ◽  
Vol 24 (7) ◽  
pp. 1061-1066 ◽  
Author(s):  
Sopio Garakanidze ◽  
Elísio Costa ◽  
Elsa Bronze-Rocha ◽  
Alice Santos-Silva ◽  
Giorgi Nikolaishvili ◽  
...  
Keyword(s):  
Risk Factor ◽  
Gene Polymorphism ◽  
Patient Group ◽  
High Frequency ◽  
Arterial Thrombosis ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Mthfr Gene Polymorphism

Methylenetetrahydrofolate reductase ( MTHFR) gene polymorphism (C677T)] is a well-recognized genetic risk factor for venous thrombosis; however, its association with arterial thrombosis is still under debate. Herein, we evaluated the prevalence of MTHFR C677T polymorphism in Georgian patients in comparison with healthy individuals and its association with arterial thrombosis. We enrolled 214 participants: 101 with arterial thrombosis (71.3% males; mean age: 66.3 ± 12.1 years) and 113 controls (67.3% males; mean age: 56.6 ± 11.3 years). Genomic DNA was extracted from dry blood spot on Whatman filter paper. Polymerase chain reaction was performed to determine MTHFR C677T polymorphism. Frequency of C677T allele polymorphism in controls was 21.2%, which corresponded to heterozygous and homozygous stage frequencies of 35.4% and 3.5%, respectively. In patient group, an allelic frequency of 33.2% was found, which corresponded to the presence of 48.5% of heterozygous and 8.9% of homozygous individuals. Comparing the frequency of mutated alleles between the 2 groups, a significantly high frequency of mutated alleles was found in patient group ( P < .05). In conclusion, high frequency of MTHFR C677T polymorphism found in arterial thrombosis patient group suggests that this polymorphism might increase the risk of arterial thrombosis in Georgian patients.

Polymorphisms of GSTP1, GSTT1, GSTM1, MTHFR, TS, ERCC1, and ERCC2 in metastatic colorectal cancer treated by first-line mFOLFOX6 chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14628-e14628
Author(s):  
K. Ishibashi ◽  
N. Okada ◽  
T. Ishiguro ◽  
M. Yokoyama ◽  
T. Miyazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Dna Repair ◽  
Metastatic Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Excision Repair ◽  
Japanese Patients ◽  
Response To Therapy ◽  
First Line ◽  
Functional Polymorphisms

e14628 Background: It was reported that determining functional polymorphisms of genes involved in drug-metabolising pathways and DNA repair may be useful for predicting the response to 5-FU/oxaliplatin chemotherapy in Caucasian patients with metastatic colorectal cancer. This study was performed to examine whether determining these polymorphisms had any clinical value in Asian patients with colorectal cancer receiving 5-FU/oxaliplatin therapy. Methods: Genomic DNA was extracted from peripheral blood lymphocytes (n=25) or colonic mucosa (n=47) in Japanese patients with metastatic colorectal cancer who were receiving first-line therapy with the modified FOLFOX6 regimen followed by FOLFIRI (n=42). Polymorphisms of 5 genes involved in drug metabolism (glutathione S-transferase (GST) P1 (IIe 105 Val), GSTT1 deletion, and GSTM1 deletion, methylenetetrahydrofolate reductase (MTHFR) (Ala 677 Val), and a 6-base pair (bp) deletion in the 3’-untranslated region (UTR) of thymidylate synthase (TS)), and polymorphisms of two DNA repair genes (excision repair cross complementing group 1 (ERCC1): Asp 118 Asn and ERCC2: Lys 751 Gln) were assessed in these patients by PCR-RFLP or the invader technique. Correlations between polymorphisms of these genes and the response to therapy were evaluated. Results: The distribution of the genotypes of GSTP1, GSTT1, TS, ERCC1, and ERCC2 in the present Japanese patients (but not that of GSTM1 or MTHFR), differed significantly from the distribution of these genotypes in a Caucasian population. The response rate and progression-free survival were not correlated with any of the functional polymorphisms investigated. However, patients who had both alleles containing the 6-bp nucleotide fragment in the 3’UTR of TS showed significantly shorter overall survival than those who had at least one allele without the 6-bp nucleotide fragment (p=0.03). Conclusions: These results suggest that 3’UTR polymorphism of TS may be an important predictor of overall survival for Japanese patients with metastatic colorectal cancer receiving first-line 5-FU/oxaliplatin therapy. No significant financial relationships to disclose.

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