Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer.

Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Research Abstract Details 

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Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Abstract Text:

Wu Zhang,Oliver A Press,Christopher A Haiman,Dong Yun Yang,Michael A Gordon,William Fazzone,Anthony El-Khoueiry,Syma Iqbal,Andy E Sherrod,Georg Lurje,Heinz-Josef Lenz,

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.

Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Publishing Authors By Initials

W Zhang,OA Press,CA Haiman,DY Yang,MA Gordon,W Fazzone,A El-Khoueiry,S Iqbal,AE Sherrod,G Lurje,HJ Lenz,

For similar investigative techniques: epidemiologic methods: data collection: vital statistics: mortality: survival rate research abstracts see: investigative techniques: epidemiologic methods: data collection: vital statistics: mortality: survival rate research

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Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of clinical oncology : official journal of

VOLUME: 25

Page Numbers: 3726-31

Journal Abbreviation: J. Clin. Oncol.

ISSN: 1527-7755

DAY: 20

MONTH: Aug

YEAR: 2007

Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8309333

Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Keywords Mesh Terms:

KEYWORDS: Survival Rate

MESH TERMS: genetics

Chemical & Substance for Abstract: Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. Information

Substance Name: Methylenetetrahydrofolate Reductase (NAD

Registry Number: EC 1.5.1.20

Grant and Affiliation Information for Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer.

AFFILIATION: Division of Medical Oncology, Department of Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.

Country: United States

AGENCY: United States NCI

GRANT: 5 P30CA14089-27L

ACRONYM: CA

MEDLINETA: J Clin Oncol

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