- Volume 13 Issue 2
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Folate intake, Methylenetetrahydrofolate Reductase Polymorphisms in Association with the Prognosis of Esophageal Squamous Cell Carcinoma
- Jing, Chen (Department of Cadre Ward, The General Hospital of Chengdu Military Area) ;
- Huang, Zhijie (Department of Nuclear Medicine, The General Hospital of Chengdu Military Area) ;
- Duan, Yuqin (Department of Cadre Ward, The General Hospital of Chengdu Military Area) ;
- Xiao, Xinrong (Department of Cadre Ward, The General Hospital of Chengdu Military Area) ;
- Zhang, Ru (Department of Cadre Ward, The General Hospital of Chengdu Military Area) ;
- Jiang, Jianqing (Department of Chest Surgery, The General Hospital of Chengdu Military Area)
- Published : 2012.02.29
Aim: An epidemiological study was conducted based on an esophageal cancer patient's cohort to investigate the association of folate intake and MTHFR C677T polymorphism with the prognosis of esophageal cancer in a Chinese population. Methods: 167 patients aged 37-75 years who had histological confirmed diagnosis of esophageal squamous cell cancer were collected from Jan. 2006 to Jan. 2008. MTHFR genotypes at the C677T site were analyzed by PCR-based RFLP methods, and the folate intake was computed by multiplying the food intake (in grams) and the folate content (per gram) of food in our questionnaire. Results: We found associations between the prognosis of esophageal cancer and smoking status, T and N stages. Individuals carrying the MTHFR 677CT and TT genotypes showed a shorter survival time than with the CC genotype, with adjusted HRs (95% CI) of 1.20 (0.56-2.15) and 2.29 (1.30-4.28), respectively. Similarly, those carrying MTHFR 677T allele had a 1.86-fold risk of death. A higher folate concentration showed a significant decreased risk of death, with an HR (95% CI) of 0.45 (0.18-0.87). Individuals with high folate intake and the MTHFR 677CC genotype showed a significant decreased risk of esophageal cancer (0.43, 0.25-0.89).Conclusion: Our findings supports the hypothesis that high folate intake and active MTHFR C677T polymorphism may exert protective roles in the prognosis of esophageal cancer in the Chinese population.
Folate intake;methylenetetrahydrofolate reductase;esophageal cancer;polymorphisms;prognosis
- Bai JL, Zheng MH, Xia X, et al (2009). MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: a meta-analysis of 3511 cases and 2762 controls. Eur J Cancer, 46, 1443-9.
- Bailey LB, Gregory JF 3rd (1999). 3rd Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr, 129, 919-922. https://doi.org/10.1093/jn/129.5.919
- Blount BC, Mack MM, Wehr CM, et al (2007). Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci USA, 94, 3290-5.
- Boccia S, Gianfagna F, Persiani R, et al (2007). Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population. Biomarkers, 12, 635-44. https://doi.org/10.1080/13547500701546766
- Cao HX, Gao CM, Takezaki T, et al (2008). Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer. Asian Pac J Cancer Prev, 9, 203-8.
- Chen H, Tucker KL, Graubard BI, et al (2002). Nutrient intakes and adenocarcinoma of the esophagus and distal stomach. Nutr Cancer, 42, 33-40. https://doi.org/10.1207/S15327914NC421_5
- Choi SW, Mason JB (2000). Folate and carcinogenesis: an integrated scheme. J Nutr, 130, 129-32. https://doi.org/10.1093/jn/130.2.129
- Esteller M (2008). Epigenetics in cancer. N Engl J Med, 358, 1148-59. https://doi.org/10.1056/NEJMra072067
- Falk GW (2009). Risk factors for esophageal cancer development. Surg Oncol Clin N Am, 18, 469-85. https://doi.org/10.1016/j.soc.2009.03.005
- Fang JY, Xiao SD (2003). Folic acid, polymorphism of methylgroup metabolism genes, and DNA methylation in relation to GI carcinogenesis. J Gastroenterol, 38, 821-9. https://doi.org/10.1007/s00535-003-1207-7
- Friso S, Choi SW, Girelli D, et al (2002). A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci USA, 99, 5606-11. https://doi.org/10.1073/pnas.062066299
- Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a commonmutation inmethylenetetrahydrofolate reductase. Nat Genet, 10, 111-3. https://doi.org/10.1038/ng0595-111
- He YT, Zhang JH, Li Y, et al (2007). Correlation between a polymorphism in the methylene tetrahydrofolate reductase gene and susceptibility to carcinoma of the esophagus and gastric cardia. Chinese J Clinic Oncol, 34, 194-7.
- Jain M, Tilak AR, Upadhyay R, et al (2008). Microsomal epoxide hydrolase (EPHX1), slow (exon 3, 113His) and fast (exon 4, 139Arg) alleles confer susceptibility to squamous cell esophageal cancer. Toxicol Appl Pharmacol, 230, 247-51. https://doi.org/10.1016/j.taap.2008.02.023
- Jiang Q, Chen K, Ma X, et al (2005). Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer. Cancer Detect Prev, 29, 146-54. https://doi.org/10.1016/j.cdp.2004.11.004
- Kim YI (2004). Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev, 13, 511-9.
- Yang CS (2000). Vitamin nutrition and gastroesophageal cancer. J Nutr, 130, S338-9. https://doi.org/10.1093/jn/130.2.338S
- Lamprecht SA, Lipkin M (2003). Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer, 3, 601-14. https://doi.org/10.1038/nrc1144
- Leclerc D, Rozen R (2007). Molecular genetics of MTHFR: polymorphisms are not all benign. Med Sci, 23, 297-302.
- Lu C, Xie H, Wang FL, et al (2011). Diet folate, DNA methylation and genetic polymorphisms of MTHFR C677T in association with the prognosis of esophageal squamous cell carcinoma. BMC Cancer, 11, 91. https://doi.org/10.1186/1471-2407-11-91
- Mayne ST, Risch HA, Dubrow R, et al (2001). Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev, 10, 1055-62.
- Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16, 1215. https://doi.org/10.1093/nar/16.3.1215
- Morita M, Kumashiro R, Kubo N, et al (2010). Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention. Int J Clin Oncol, 15, 126-34. https://doi.org/10.1007/s10147-010-0056-7
- Wang JM, Xu B, Rao JY, et al (2007). Diet habits, alcohol drinking, tobacco smoking, green tea drinking, and the risk of esophageal squamous cell carcinoma in the Chinese population. Eur J Gastroenterol Hepatol, 19, 171-6. https://doi.org/10.1097/MEG.0b013e32800ff77a
- Wang Y, Guo W, He Y, et al (2007). Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China. Cancer Causes Control, 18, 143-52. https://doi.org/10.1007/s10552-006-0097-4
- Sarbia M, Stahl M, von Weyhern C, et al (2006). The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma. Br J Cancer, 94, 203-7. https://doi.org/10.1038/sj.bjc.6602900
- Shen H, Spitz MR, Wang LE, et al (2001). Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. Cancer Epidemiol Biomarkers Prev, 10, 397-401.
- Shitara K, Muro K, Ito S, et al (2010). Folate intake along with genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase in patients with advanced gastric cancer. Cancer Epidemiol Biomarkers Prev, 19, 1311-9. https://doi.org/10.1158/1055-9965.EPI-09-1257
- Stolzenberg-Solomon RZ, Qiao YL, Abnet CC, et al (2003). Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev, 12, 1222-6.
- Sun SX (2011). Folate Intake, Methylenetetrahydrofolate reductase Polymorphisms in association with esophageal squamous cell carcinoma. Asian Pac J Cancer Prev, 11, In press.
- Suzuki T, Matsuo K, Hasegawa Y, et al (2007). One-carbon metabolism-related gene polymorphisms and risk of head and neck squamous cell carcinoma: case-control study. Cancer Sci, 98, 1439-46. https://doi.org/10.1111/j.1349-7006.2007.00533.x
- Shrubsole MJ, Jin F, Dai Q, et al (2001). Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res, 61, 7136-41.
- Stern LL, Mason JB, Selhub J, et al (2000). Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev, 9, 849-53.
- Turek-Plewa J, Jagodzinski PP (2005). The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett, 10, 631-47.
- Umar M, Upadhyay R, Khurana R, et al (2010). Evaluation of MTHFR677C>T polymorphism in prediction and prognosis of esophageal squamous cell carcinoma: a case-control study in a northern Indian population. Nutr Cancer, 62, 743-9. https://doi.org/10.1080/01635581003605961
- Ulrich C (2010). Linking epidemiology to epigenomics-where are we today? Cancer Prev Res, 3, 1505-8. https://doi.org/10.1158/1940-6207.CAPR-10-0298
- Upadhyay R, Jain M, Kumar S, et al (2008). Association of interleukin-6 (-174G>C) promoter polymorphism with risk of squamous cell esophageal cancer and tumor location: an exploratory study. Clin Immunol, 128, 199-204. https://doi.org/10.1016/j.clim.2008.03.519
- Wilcken B, Bamforth F, Li Z, et al (2003). Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide. J Med Genet, 40, 619-25. https://doi.org/10.1136/jmg.40.8.619
- Xu WH, Shrubsole MJ, Xiang YB, et al (2007). Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev, 16, 281-7. https://doi.org/10.1158/1055-9965.EPI-06-0798
- Yang CX, Matsuo K, Ito H, et al (2005). Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case-control study in Japan. Carcinogenesis, 26, 1285-90. https://doi.org/10.1093/carcin/bgi076
- Yu MC, Yuan JM, Lu SC (2008). Alcohol, cofactors, and the genetics of hepatocellular carcinoma. J Gastroenterol Hepatol, 23, S92-7. https://doi.org/10.1111/j.1440-1746.2007.05293.x
- Zhang J, Zotz RB, Li Y, et al (2004). Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamouscell carcinoma in a German Caucasian and a northern Chinese population. J Cancer Res Clin Oncol, 130, 574-80.
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