Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer.

Xiaoping Zhang; Zhibin Bai; Baoan Chen; Jifeng Feng; Feng Yan; Zhi Jiang; Yuejiao Zhong; Jianzhong WU; Lu Cheng; Zuhong LU; Na Tong; Zhengdong Zhang

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Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer.

Author: Xiaoping ZHANG ^{1
,

2} ; Zhibin BAI ³ ; Baoan CHEN ¹ ; Jifeng FENG ⁴ ; Feng YAN ⁴ ; Zhi JIANG ⁴ ; Yuejiao ZHONG ⁴ ; Jianzhong WU ⁴ ; Lu CHENG ⁵ ; Zuhong LU ⁵ ; Na TONG ⁶ ; Zhengdong ZHANG ⁶
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1. Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, China
2. Department of Oncology, Medical School, Southeast University, Nanjing, Jiangsu 210009, China.
3. Department of Invasive Technology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, China
4. Jiangsu Province Cancer Institute, Nanjing, Jiangsu 210009, China.
5. Department of Oncology, Medical School, Southeast University, Nanjing, Jiangsu 210009, China
6. Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Publication Type:Journal Article
MeSH: Adolescent; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; therapeutic use; Asian Continental Ancestry Group; Female; Fluorouracil; therapeutic use; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); genetics; Middle Aged; Prospective Studies; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stomach Neoplasms; drug therapy; enzymology; genetics; Young Adult
From: Chinese Medical Journal 2014;127(20):3562-3567
CountryChina
Language:English
Abstract:
BACKGROUNDThe importance of polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear. The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.
METHODSThree hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy. DNA samples were isolated from peripheral blood collected before treatment. The three single nucleotide polymorphisms (SNPs) (rs1801131, rs1801133, rs2274976) genotypes of the MTHFR gene were determined by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
RESULTSThe average response rate for chemotherapy was 46.7%. Homozygous genotypes rs2274976G/G (χ(2) = 22.7, P < 0.01) and rs1801131A/A (χ(2) = 14.3, P = 0.008) were over-represented in responsive patients. Carriers of the rs2274976A allele genotypes (G/A and A/A) and of the rs1801131C allele genotypes (A/C and C/C) were prevalent in nonresponsive patients. In the haplotype association analysis, there was a significant difference in global haplotype distribution between the groups (χ(2) = 20.69, P = 0.000 124).
CONCLUSIONSThese results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.