Association of Methylenetetrahydrofolate Reductase Gene Polymorphisms and Sex-Specific Survival in Patients With Metastatic Colon Cancer

2007 ◽  
Vol 25 (24) ◽  
pp. 3726-3731 ◽  
Author(s):  
Wu Zhang ◽  
Oliver A. Press ◽  
Christopher A. Haiman ◽  
Dong Yun Yang ◽  
Michael A. Gordon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Southern California ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Comprehensive Cancer Center ◽  
Metastatic Colon Cancer ◽  
University Of Southern California ◽  
A1298c Polymorphism

Purpose Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating intracellular folate levels, which affects DNA synthesis and methylation. Two MTHFR gene polymorphisms, C677T and A1298C, are linked to altered enzyme activity. Several studies have shown these two polymorphisms to be associated with response to fluorouracil (FU) -based treatment in advanced colon cancer patients, but data are inconsistent and contradictory. Meanwhile, epidemiologic studies demonstrated that these MTHFR polymorphisms were associated with cancer risk in a sex-specific manner. We tested the hypothesis of whether these two polymorphisms are associated with sex-specific clinical outcome in metastatic colon cancer patients treated with FU-based chemotherapy. Patients and Methods This study included 318 patients (177 men and 141 women) with metastatic colon cancer treated between 1992 and 2003 at the University of Southern California/Norris Comprehensive Cancer Center or Los Angeles County/University of Southern California Medical Center. Peripheral blood samples were collected from each patient, and genomic DNA was extracted from WBCs. Two MTHFR gene polymorphisms (C677T and A1298C) were tested by fluorogenic 5′-nuclease assay. Results The A1298C polymorphism showed statistically significant differences in overall survival (OS) in female, but not male, patients with metastatic colon cancer (log-rank test, P = .038). Among females, OS was greater for patients with the A/A genotype (n = 67; median OS, 18.4 months) compared with patients with the A/C genotype (n = 50; median OS, 13.9 months) or C/C genotype (n = 10; median OS, 15.6 months). Conclusion Although preliminary, these data support the role of the A1298C polymorphism in MTHFR as prognostic marker in female patients with metastatic colon cancer. Further studies are needed to confirm these findings.

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms associated with overall survival in women with metastatic colon cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3600-3600
Author(s):  
O. A. Press ◽  
W. Zhang ◽  
D. Yang ◽  
C. A. Haiman ◽  
M. Gordon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Metastatic Colon Cancer ◽  
University Of Southern California ◽  
Mthfr A1298c

3600 Background: Methylenetetrahydrofolate Reductase (MTHFR) is a key enzyme regulating intracellular folate pool, which affects DNA synthesis and methylation. Recent studies found folate deficiency induces DNA damage because of impaired nucleotide-excision repairs in mouse model. Two MTHFR gene polymorphisms, C677T and A1298C are linked to altered enzyme activity. Numerous studies have shown these two polymorphisms associated with colon cancer risk and response to fluorouracil-based treatment in advanced colon cancer patients. One epidemiology study also demonstrated 1298CC genotype to be associated with a significantly lower risk of colon cancer in women, but not men. We tested whether these two polymorphisms were associated with clinical outcome in metastatic colon cancer patients treated with 5-FU/Oxaliplatin. Methods: Between 1992 and 2003, a total of 318 patients with metastatic colon cancer treated at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC) or the Los Angeles County/University of Southern California Medical Center (LAC/USCMC), were eligible for this study. Peripheral blood samples were collected from each patient and genomic DNA was extracted from white blood cells using the QiaAmp kit (Qiagen, Valencia, CA). Two MTHFR gene polymorphisms (C677T, A1298C) were tested by PCR-RFLP method. Results: MTHFR A1298C gene polymorphism showed statistically significant differences in overall survival (OS) in female patients with metastatic colon cancer (P=0.025, logrank test). Patients with the AA genotype had an 18.7 months median OS compared with the heterozygous AC genotype, which had a 14.3 months median OS and the CC genotype, which had a 15.9 months median OS. Conclusions: There is no significant difference in clinical outcome in male patients. However, female metastatic colon cancer patients with a MTHFR A1298C polymorphism AA genotype have significantly better overall survival than those with heterozygous AC genotype or CC genotype. This data supports the role of MTHFR polymorphisms as an independent prognostic marker in female patients with metastatic colon cancer. Further prospective study is needed to confirm these preliminary findings. [Table: see text]

scholarly journals Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients

2010 ◽  
Vol 69 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Marie-Christine Etienne-Grimaldi ◽  
Gérard Milano ◽  
Frédérique Maindrault-GÅ“bel ◽  
Benoist Chibaudel ◽  
Jean-Louis Formento ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Colorectal Cancer Patients

Correlation between Methylenetetrahydrofolate Reductase Polymorphisms and Hepatocellular Carcinoma: A Meta-Analysis

2019 ◽  
Vol 74 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Hailong Su ◽  
Guo Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Random Effect ◽  
Recessive Model ◽  
Mthfr Gene ◽  
Systematic Research ◽  
The Relationship ◽  
Random Effect Models

Background: The correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) remains controversial. Objectives: We performed this study to better assess the relationship between MTHFR gene polymorphisms and the likelihood of HCC. Methods: A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. ORs and 95% CIs were calculated. Results: A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models (FEMs) in recessive comparison (p = 0.002, OR 0.62, 95% CI 0.43–0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: p < 0.0001, OR 0.42, 95% CI 0.29–0.62; allele model: p = 0.004, OR 1.20, 95% CI 1.06–1.35) and random-effect models (recessive model: p = 0.002, OR 0.47, 95% CI 0.29–0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. Conclusions: Our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.

scholarly journals Sequential Therapies and the Cost-Effectiveness of Treating Metastatic Colon Cancer Patients

2016 ◽  
Vol 22 (6) ◽  
pp. 628-639 ◽  
Author(s):  
Andinet Woldemichael ◽  
Eberechukwu Onukwugha ◽  
Brian Seal ◽  
Nader Hanna ◽  
C. Daniel Mullins
Keyword(s):  
Colon Cancer ◽  
Cost Effectiveness ◽  
Cancer Patients ◽  
Metastatic Colon Cancer ◽  
The Cost

scholarly journals he effects of NETosis on fibrinolysis in colon cancer patients

2022 ◽  
Vol 20 (4) ◽  
pp. 25-31
Author(s):  
A. A. Parshina ◽  
N. N. Tsybikov ◽  
P. P. Tereshkov ◽  
T. M. Karavaeva ◽  
M. V. Maksimenya
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cell Activation ◽  
Fluorescent Microscopy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Metastatic Colon Cancer ◽  
The Given ◽  
Experimental Group ◽  
Pai 1

Aim. To investigate formation of neutrophil extracellular traps (NETs) and their impact on fibrinolysis in patients with colon cancer.Materials and methods. The study was performed in two groups. The experimental group consisted of patients with stage 2–3 non-metastatic colon cancer (n = 17, average age – 67 years). The control group included healthy volunteers matched by sex and age (n = 30, average age – 68 years). An experimental model was created from the whole blood. It included platelet-poor plasma and an isolated culture of neutrophils, previously induced to NETosis by adding 100 nmol PMA. The samples were incubated for 4 hours, then the test tubes were centrifuged to pellet cells and their remnants, and the plasma was transferred for subsequent examination. The plasma incubated with intact neutrophils was used as a control. The levels of interleukin-8 (IL-8) and P-selectin glycoprotein ligand-1 (PSGL-1) were used to determine the degree of cell activation. NETosis was confirmed by enzyme-linked immunosorbent assay (ELISA) and fluorescent microscopy. Fibrinolysis was assessed using the thrombodynamics test. The results were compared with the levels of fibrinolytic system components measured by flow cytometry.Results. In the control group, NETosis induction contributed to pronounced neutrophil activation that was accompanied by an increase in the IL-8, PSGL-1, and plasminogen levels, a decrease in PAI-1, and enhancement of fibrinolysis, compared with the intact samples. Higher levels of IL-8, PSGL-1, plasminogen, and PAI-1 and intensified fibrinolysis were detected in the intact samples. However, PMA-induced NETosis did not result in an increase in the degree of activation and significant changes in the given parameters.Conclusion. NETosis promotes both formation and lysis of fibrin clots. However, in cancer patients, suicidal NETosis does not contribute to fibrinolysis due to intracellular protease depletion, which may be one of the mechanisms causing hypercoagulation and insufficient fibrinolysis in cancer. 

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