Colon Cancer and Genetic Variation in Folate Metabolism: The Clinical Bottom Line

Journal of Nutrition

Volumn 133, Issue 11 SUPPL. 1, 2003, Pages

  Little, Julian ^a   Sharp, Linda ^c   Duthie, Susan ^b   Narayanan, Sabrina ^b  

^a NATIONAL CENTER ON BIRTH DEFECTS AND DEVELOPMENTAL DISABILITIES   (United States)

^b ROWETT RESEARCH INSTITUTE   (United Kingdom)

^c NONE

Author keywords

Colorectal neoplasia; Epidemiology prevention; Folate; Methylenetetrahydrofolate reductase; Treatment

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); CYSTATHIONINE BETA SYNTHASE; DNA; FOLIC ACID; METHIONINE SYNTHASE; THYMIDYLATE SYNTHASE;

COLON ADENOMA; COLON CANCER; CONFERENCE PAPER; DIETARY INTAKE; DNA SYNTHESIS; ENVIRONMENTAL FACTOR; FOLATE METABOLISM; GENE FUNCTION; GENE LINKAGE DISEQUILIBRIUM; GENETIC VARIABILITY; GENOTYPE; HUMAN; POPULATION RESEARCH; PRIMARY PREVENTION; SAMPLE SIZE; VEGETABLE;

EID: 0242442499     PISSN: 00223166     EISSN: None     Source Type: Journal    
DOI: 10.1093/jn/133.11.3758s     Document Type: Conference Paper

References (113)

1. Collins, F. S., Green, E. D., Guttmacher, A. E. & Guyer, M. S. (2003) A vision for the future of genomics research. Nature 422: 835-847.
2. World Cancer Research Fund & American Institute for Cancer Research. (1997) Food, Nutrition and the Prevention of Cancer: A Global Perspective. American Institute for Cancer Research, Washington, DC.
3. International Agency for Cancer Research Working Group. (2003) IARC handbooks of cancer prevention. Vol. 8: Fruits and vegetables. IARC Press, Lyon, France.
4. Klerk, M., Verhoef, P., Clarke, R., Blom, H. J., Kok, F. J. & Schouten, E. G. (2002) MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. J. Am. Med. Assoc. 288: 2023-2031.
5. Homocysteine Studies Collaboration. (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J. Am. Med. Assoc. 288: 2015-2022.
6. Ames, B. N. (1999) Cancer prevention and diet: help from single nucleotide polymorphisms. Proc. Natl. Acad. Sci. U.S.A. 96: 12216-12218.
7. Muller, M. & Kersten, S. (2003) Nutrigenomics: goals and strategies. Nat. Rev. Genet. 4: 315-322.
8. King, J. (2003) Nutritional genomics. Interview by Deborah Shattuck. J. Am. Diet. Assoc. 103: 16-18.
9. Barrett, S. & Hall, H. Dubious genetic testing. http://www.quackwatch.org/01QuackeryRelatedTopics/Tests/genomics.html (accessed July 10, 2003).
10. Williams-Jones, B. (2003) Where there's a web, there's a way: commercial genetic testing and the Internet. Community Genet. 6: 46-57.
11. Feskanich, D., Ziegler, R. G., Michaud, D. S., Giovannucci, E. L., Speizer, F. E., Willett, W. C. & Colditz, G. A. (2000) Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J. Natl. Cancer Inst. 92: 1812-1823.
12. Michels, K. B., Giovannucci, E., Joshipura, K. J., Rosner, B. A., Stampfer, M. J., Fuchs, C. S., Colditz, G. A., Speizer, F. E. & Willett, W. C. (2000) Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J. Natl. Cancer Inst. 92: 1740-1752.
13. Voorrips, L. E., Goldbohm, R. A., van Poppel, G., Sturmans, F., Hermus, R. J. & van den Brandt, P. A. (2000) Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: The Netherlands Cohort Study on Diet and Cancer. Am. J. Epidemiol. 152: 1081-1092.
14. Smith-Warner, S. A., Spiegelman, D., Yaun, S. S., Adami, H. O., Beeson, W. L., van den Brandt, P. A., Folsom, A. R., Fraser, G. E., Freudenheim, J. L., Goldbohm, R. A., Graham, S., Miller, A. B., Potter, J. D., Rohan, T. E., Speizer, F. E., Toniolo, P., Willett, W. C., Wolk, A., Zeleniuch-Jacquotte, A. & Hunter, D. J. (2001) Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. J. Am. Med. Assoc. 285: 769-776.
15. Flood, A., Velie, E. M., Chaterjee, N., Subar, A. F., Thompson, F. E., Lacey, J. V., Jr., Schairer, C., Troisi, R. & Schatzkin, A. (2002) Fruit and vegetable intakes and the risk of colorectal cancer in the Breast Cancer Detection Demonstration Project follow-up cohort. Am. J. Clin. Nutr. 75: 936-943.
16. Sharp, L. & Little, J. (2003) Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and colorectal neoplasia. In: Human Genome Epidemiology: A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease (Khoury, M. J., Little, J. & Burke, W., eds.). Oxford University Press, New York, NY.
17. Herbert, V. (1987) Recommended dietary intakes (RDI) of folate in humans. Am. J. Clin. Nutr. 45: 661-670.
18. Cotton, S., Sharp, L. & Little, J. (1996) The adenoma-carcinoma sequence and prospects for the prevention of colorectal neoplasia. Cdt. Rev. Oncog. 7: 293-342.
19. Clayton, D. & Hills, M. (1993) Statistical Models in Epidemiology. Oxford University Press, Oxford, U.K.
20. Paspatis, G., Xourgias, B., Mylonakou, E., Zisis, D., Barbagianis, G. & Karamanolis, D. (1994) A prospective clinical trial to determine the influence of folate supplementation on the formation of recurrent colonic adenomas. Gastroenterology 106: 425(abs.).
21. Youngman, L. D., Keavney, B. D., Palmer, A., Parish, S., Clark, S., Danesh, J., Delepine, M., Lathrop, M., Peto, R. & Collins, R. (2000) Plasma fibrinogen and fibrinogen genotypes in 4685 cases of myocardial infarction and in 6002 controls: test of causality by "Mendelian randomisation". Circulation 102 (suppl II): 31-32.
22. Davey Smith, G. & Ebrahim, S. (2003) 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32: 1-22.
23. Clayton, D. & McKeigue, P. M. (2001) Epidemiological methods for studying genes and environmental factors in complex diseases. Lancet 358: 1356-1360.
24. Johnson, W. G. (1999) DNA polymorphism-diet-cofactor-development hypothesis and the gene-teratogen model for schizophrenia and other developmental disorders. Am. J. Med. Genet. 88: 311-323.
25. Rozen, R. (1997) Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb. Haemost. 78: 523-526.
26. van der Put, N. M. J., Gabreëls, F., Stevens, E. M. B., Smeitink, J. A. M., Trijbels, F. J. M., Eskes, T. K. A. B., van den Heuvel, L. P. & Blom, H. J. (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am. J. Hum. Genet. 62: 1044-1051.
27. Weisberg, I., Tran, P., Christensen, B., Sibani, S. & Rozen, R. (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol. Genet. Metab. 64: 169-172.
28. Ma, J., Stampfer, M. J., Giovannucci, E., Artigas, C., Hunter, D. J., Fuchs, C., Willett, W. C., Selhub, J., Hennekens, C. H. & Rozen, R. (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions and risk of colorectal cancer. Cancer Res. 57: 1098-1102.
29. 12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol. Biomarkers Prev. 8: 825-829.
30. Molloy, A. M., Daly, S., Mills, J. L., Kirke, P. N., Whitehead, S. S., Ramsbottom, D., Conley, M. R., Weir, D. G. & Scott, J. M. (1997) Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet 349: 1591-1593.
31. Friedman, G., Goldschmidt, N., Friedlander, Y., Ben-Yehuda, A., Selhub, J., Babaey, S., Mendel, M., Kidron, M. & Bar-On, H. (1999) A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. J. Nutr. 129: 1656-1661.
32. Chango, A., Boisson, F., Barbé, F., Quilliot, D., Droesch, S., Pfister, M., Fillon-Emery, N., Lambert, D., Frémont, S., Rosenblatt, D. S. & Nicolas, J. P. (2000) The effect of 677C-T and 1298A-C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br. J. Nutr. 83: 593-596.
33. Lievers, K. J. A., Boers, G. H. J., Verhoef, P., den Heijer, M., Kluijtmans, L. A. J., van der Put, N. M. J., Trijbels, F. J. M. & Blom, H. J. (2001) A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J. Mol. Med. 79: 522-528.
34. Chen, J., Ma, J., Stampfer, M. J., Palomeque, C., Selhub, J. & Hunter, D. J. (2002) Linkage disequilibrium between the 677C>T and 1298A>C polymorphisms in human methylenetetrahydrofolate reductase gene and their contributions to risk of colorectal cancer. Pharmacogenetics 12: 339-342.
35. Botto, L. D. & Yang, Q. (2000) 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am. J. Epidemiol. 151: 862-877.
36. Narayanan, S. (2001) The effect of folic acid and genetic polymorphisms on DNA stability and colorectal cancer. Doctoral thesis, University of Aberdeen, Aberdeen, U.K.
37. Zijno, A., Andreoli, C., Leopardi, P., Marcon, F., Rossi, S., Caiola, S., Verdina, A., Galati, R., Cafolla, A. & Crebelli, R. (2003) Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects. Carcinogenesis 24: 1097-1103.
38. Crott, J. W., Mashiyama, S. T., Ames, B. N. & Fenech, M. F. (2001) Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro. Carcinogenesis 22: 1019-1025.
39. Andreassi, M. G., Botto, N., Cocci, F., Battaglia, D., Antonioli, E., Masetti S., Manfredi, S., Colombo, M. G., Biagini, A. & Clerico, A. (2003) Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine, vitamin B12, and DNA damage in coronary artery disease. Hum. Genet. 112: 171-177.
40. Zeisel, S. H., Allen, L. H., Coburn, S. P., Erdman, J. W., Failla, M. L. Freake, H. C., King, J. C. & Storch, J. (2001) Nutrition: a reservoir for integrative science. J. Nutr. 131: 1319-1321.
41. Ardlie, K. G., Kruglyak, L. & Seielstad, M. (2002) Patterns of linkage disequilibrium in the human genome. Nat. Rev. Genet. 3: 299-309.
42. Pritchard, J. K. & Przeworski, M. (2001) Linkage disequilibrium in humans: models and data. Am. J. Hum. Genet. 69: 1-14.
43. Ogino, S. & Wilson, R. B. (2003) Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta analysis. J. Hum. Genet. 48: 1-7.
44. Hirschhorn, J. N., Lohmueller, K., Byme, E. & Hirschhorn, K. (2002) A comprehensive review of genetic association studies. Genet. Med. 4: 45-61.
45. Le Marchand, L., Donlon, T., Hankin, J. H., Kolonel, L. N., Wilkens, L. R. Seifried, A. (2002) B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes Control 13: 239-248.
46. Keku, T., Millikan, R., Worley, K., Winkel, S., Eaton, A., Biscocho, L. Martin, C. & Sandler, R. (2002) 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites. Cancer Epidemiol. Biomarkers Prev. 11: 1611-1621.
47. Matsuo, K., Hamajima, N., Hirai, T., Kato, T., Inoue, M., Takezaki, T. & Tajima, K. (2002) Methionine synthase reductase gene A66G polymorphism is associated with risk of colorectal cancer. Asian Pac. J. Cancer Prev. 3: 353-359.
48. Sharp, L., Little, J., Brockton, N., Cotton, S. C., Haites, N. E. & Cassidy, J. (2002) Dietary intake of folate and related micronutrients, genetic polymorphisms in MTHFR and colorectal cancer: a population-based case-control study in Scotland. J. Nutr. 132: 3542S.
49. Plaschke, J., Schwanebeck, U., Pistorius, S., Saeger, H. D. & Schackert, H. K. (2003) Methylenetetrahydrofolate reductase polymorphisms and risk of sporadic and hereditary colorectal cancer with or without microsatellite instability. Cancer Lett. 191: 179-185.
50. Thomas, D. C. & Witte, J. S. (2002) Point: population stratification: a problem for case-control studies of candidate-gene associations? Cancer Epidemiol. Biomarkers Prev. 11: 505-512.
51. Wacholder, S., Rothman, N. & Caporaso, N. (2002) Counterpoint: bias from population stratification is not a major threat to the validity of conclusions from epidemiological studies of common polymorphisms and cancer. Cancer Epidemiol. Biomarkers Prev. 11: 513-520.
52. Cardon, L. R. & Palmer, L. J. (2003) Population stratification and spurious allelic association. Lancet 361: 598-604.
53. Wacholder, S., Rothman, N. & Caporaso, N. (2000) Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias. J. Natl. Cancer Inst. 92: 1151-1158.
54. Ardlie, K. G., Lunetta, K. L. & Seielstad, M. (2002) Testing for population subdivision and association in four case-control studies. Am. J. Hum. Genet. 71: 304-311.
55. Editorial. (1999) Freely associating. Nat. Genet. 22: 1-2.
56. Cardon, L. R. & Bell, J. I. (2001) Association study designs for complex diseases. Nat. Rev. Genet. 2: 91-99.
57. Ioannidis, J. P., Ntzani, E. E., Trikalinos, T. A. & Contopoulos-Ioannidis, D. G. (2001) Replication validity of genetic association studies. Nat. Genet. 29: 306-309.
58. Collins, R. & MacMahon, S. (2001) Reliable assessment of the effects of treatment on mortality and major morbidity: I: Clinical trials. Lancet 357: 373-380.
59. Sharp, L. & Little, J. (2003) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am. J. Epidemiol. (in press)
60. Little, J., Bradley, L., Bray, M. S., Clyne, M., Dorman, J., Ellsworth, D. L., Hanson, J., Khoury, M., Lau, J., O'Brien, T. R., Rothman, N., Stroup, D., Taioli, E., Thomas, D., Vainio, H., Wacholder, S. & Weinberg, C. (2002) Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. Am. J. Epidemiol. 156: 300-330.
61. Delgado-Enciso, I., Martinez-Garza, S. G., Rojas-Martinez, A., Ortiz-Lopez, R., Bosques-Padilla, F., Calderon-Garciduenas, A. L., Zarate-Gomez, M. & Barrera-Saldana, H. A. (2001) 677T mutation of the MTHFR gene in adenomas and colorectal cancer in a population sample from the Northeastern Mexico. Rev. Gastroenterol. Mex. 66: 32-37.
62. Ryan, B. M., Molloy, A. M., McManus, R., Arfin, Q., Kelleher, D., Scott, J. M. & Weir, D. G. (2001) The methelenetetrahydrofolate reductase (MTHFR) gene in colorectal cancer. Int. J. Gastrointest. Cancer 30: 105-111.
63. Editorial. (2003) In search of genetic precision. Lancet 361: 357.
64. Little, J., Khoury, M. J., Bradley, L., Clyne, M., Gwinn, M., Lin, B., Lindegren, M. L. & Yoon, P. (2003) The Human Genome project is complete. How do we develop a handle for the pump? Am. J. Epidemiol. 157: 667-673.
65. Khoury, M. J., Stewart, W. & Beaty, T. H. (1987) The effect of genetic susceptibility on causal inference in epidemiologic studies. Am. J. Epidemiol. 126: 561-567.
66. Khoury, M. J., Adams, M. J., Jr. & Flanders, W. D. (1988) An epidemiologic approach to ecogenetics. Am. J. Hum. Genet. 42: 89-95.
67. Levine, A. J., Siegmund, K. D., Ervin, C. M., Diep, A., Lee, E. R., Franki, H. D. & Haile, R. W. (2000) The methylenetetrahydrofolate reductase 677C→T polymorphism and distal colorectal adenoma risk. Cancer Epidemiol. Biomarkers Prev. 9: 657-663.
68. Ulrich, C. M., Kampman, E., Bigler, J., Schwartz, S. M., Chen, C., Bostick, R., Fosdick, L., Beresford, S. A. A., Yasui, Y. & Potter, J. D. (1999) Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? Cancer Epidemiol. Biomarkers Prev. 8: 659-668.
69. Little, J. (2003) Reporting and Review of Human Genome Epidemiology Studies. In: Human Genome Epidemiology. A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease (Khoury, M. J., Little, J. & Burke, W., eds.). Oxford University Press, New York, NY.
70. Garcia-Closas, M., Rothman, N. & Lubin, J. (1999) Misclassification in case-control studies of gene-environment interactions. assessment of bias and sample size. Cancer Epidemiol. Biomarkers Prev. 8: 1043-1050.
71. Chen, J., Giovannucci, E., Kelsy, K., Rimm, E. B., Stampfer, M. J., Colditz, G. A., Spiegelman, D., Willett, W. C. & Hunter, D. J. (1996) A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 56: 4862-4864.
72. Botto, L. D. & Khoury, M. J. (2003) Facing the challenge of complex genotypes and gene-environment interaction: the basic epidemiologic units in case-control and case-only designs. In: Human Genome Epidemiology. A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease (Khoury, M. J., Little, J. & Burke, W., eds.). Oxford University Press, New York, NY.
73. Slattery, M. L., Potter, J. D., Samowitz, W., Schaffer, D. & Leppert, M. (1999) Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol. Biomarkers Prev. 8: 513-518.
74. Nallamothu, B. K., Fendrick, A. M., Rubenfire, M., Saint, S., Bandekar, R. R. & Omenn, G. S. (2000) Potential clinical and economic effects of homocyst(e)ine lowering. Arch. Intern. Med. 160: 3406-3412.
75. Wolf, C. R. & Smith, G. (1999) Cytochrome p450 CYP2D6. In: Metabolic Polymorphisms and Susceptibility to Cancer. Vol. 148. (Vineis, P., Malats, N., Lang, M., d'Errico, A., Caporaso, N., Cuzick, J. & Boffetta, P., eds.), pp. 209-229. IARC Scientific Publications, International Agency for Research on Cancer, Lyon, France.
76. Sing, C. F., Stengard, J. H. & Kardia, S. L. (2003) Genes, environment, and cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 23: 1190-1196.
77. Choi, S. W. & Friso, S. (2001) Is it worthwhile to try different coenzymatic forms of folate in future chemoprevention trials? Nutrition 17: 738-739.
78. Akoglu, B., Faust, D., Milovic, V. & Stein, J. (2001) Folate and chemoprevention of colorectal cancer: is 5-methyltetrahydrofolate an active antiproliferative agent in folate-treated colon-cancer cells? Nutrition 17: 652-653.
79. Cuskelly, G. J., McNulty, H. & Scott, J. M. (1996) Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet 347: 657-659.
80. Jacques, P. F., Selhub, J., Bostom, A. G., Wilson, P. W. F. & Rosenberg, I. H. (1999) The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N. Engl. J. Med. 340: 1449-1454.
81. Wald, N. J., Law, M. R., Morris, J. K. & Wald, D. S. (2001) Quantifying the effect of folic acid. Lancet 358: 2069-2073.
82. Kim, Y. I., Fawaz, K., Knox, T., Lee, Y. M., Norton, R., Arora, S., Paiva, L. & Mason, J. B. (1998) Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps. Am. J. Clin. Nutr. 68: 866-872.
83. Kim, Y. I., Fawaz, K., Knox, T., Lee, Y. M., Norton, R., Libby, E. & Mason, J. B. (2001) Colonic mucosal concentrations of folate are accurately predicted by blood measurements of folate status among individuals ingesting physiologic quantities of folate. Cancer Epidemiol. Biomarkers Prev. 10: 715-719.
84. Nelen, W. L. D. M., Blom, H. J., Thomas, C. M. G., Steegers, E. A. P., Boers, G. H. J. & Eskes, T. K. A. B. (1998) Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from tow low dose folic acid supplementation in women with unexplained recurrent miscarriages. J. Nutr. 128: 1336-1341.
85. Woodside, J. V., Yarnell, J. W., McMaster, D., Young, I. S., Harmon, D. L., McCrum, E. E., Patterson, C. C., Gey, K. F., Whitehead, A. S. & Evans, A. (1998) Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomised, factorial-design, controlled trial. Am. J. Clin. Nutr. 67: 858-866.
86. Hauser, A. C., Hagen, W., Rehak, P. H., Buchmayer, H., Foëdinger, M., Papagiannopoulos, M., Bieglmayer, C., Apsner, R., Koëller, E., Ignatescu, M., Hoërl, W. H. & Sunder-Plassmann, G. (2001) Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients. Am. J. Kidney Dis. 37: 758-765.
87. Pullin, C. H., Ashfield-Watt, P. A. L., Burr, M. L., Clark, Z. E., Lewis, M. J., Moat, S. J., Newcombe, R. G., Stats, C., Powers, H. J., Whiting, J. M. & McDowell, I. F. W. (2001) Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance enothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype. J. Am. Coll. Cardiol. 38: 1799-1805.
88. Fohr, I. P., Prinz-Langenohl, R., Brönstrup, A., Bohlmann, A. M., Nau, H., Berthold, H. K. & Pietrzik, K. (2002) 5,10-methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am. J. Clin. Nutr. 75: 275-282.
89. Vineis, P., Schulte, P. & McMichael, A. J. (2001) Misconceptions about the use of genetic tests in populations. Lancet 357: 709-712.
90. Yang, Q., Khoury, M. J., Botto, L., Friedman, J. M. & Flanders, W. D. (2003) Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes. Am. J. Hum. Genet. 72: 636-649.
91. Little, J. (1995) Is folic acid pluripotent? A review of the associations with congenital anomalies, cancer and other diseases. In: Drugs, Diet and Disease. Vol. 1. Mechanistic Approaches to Cancer (Ioannides, C. & Lewis, D. F. V., eds.), pp. 259-308. Ellis Horwood, New York, NY.
92. Stumpf, D. A. (2003) Symptoms of B(12) deficiency can occur in women of childbearing age supplemented with folate. Neurology 60: 353.
93. 12. Schweizerische Zeitschdft fur Ganzheitsmedizin 14: 64-74.
94. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Institute of Medicine (2000) Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academy Press, Washington, DC.
95. Green, T. J., Skeaff, C. M., Whiting, S. J. & Gibson, R. S. (2003) Effect of folic acid supplementation on plasma zinc concentrations of young women. Nutrition 19: 522-523.
96. Khosraviani, K., Weir, H. P., Hamilton, P., Moorehead, J. & Williamson, K. (2002) Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer. Gut 51: 195-199.
97. U.S. Preventive Services Task Force. (2003) Routine vitamin supplementation to prevent cancer and cardiovascular disease: recommendations and rationale. Ann. Intern. Med. 139: 51-55.
98. Wisotzkey, J. D., Toman, J., Bell, T., Monk, J. S. & Jones, D. (1999) MTHFR (C677T) polymorphisms and stage III colon cancer: response to therapy. Mol. Diagn. 4: 95-99.
99. Shannon, B., Gnanasampanthan, S., Beilby, J. & Iacopetta, B. (2002) A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability. Gut 50: 520-524.
100. Cohen, V., Panet-Raymond, V., Sabbaghian, N., Morin, I., Batist, G. & Rozen, R. (2003) Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy. Clin. Cancer Res. 9: 1611-1615.
101. Ulrich, C. M., Yasui, Y., Storb, R., Schubert, M. M., Wagner, J. L., Bigler, J., Ariail, K. S., Keener, C. L., Li, S., Liu, H., Farin, F. M. & Potter, J. D. (2001) Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 98: 231-234.
102. Toffoli, G., Veronesi, A., Boiocchi, M. & Crivellari, D. (2000) MTHFR gene polymorphism and severe toxicity during adjuvant treatment of early breast cancer with cyclophosphamide, methotrexate, and fluorouracil (CMF). Ann. Oncol. 11: 373-374.
103. Etienne, M. C., Chazai, M., Laurent-Puig, P., Magne, N., Rosty, C., Formento, J. L., Francoual, M., Formento, P., Renee, N., Chamorey, E., Bourgeon, A., Seitz, J. F., Delpero, J. R., Letoublon, C., Pezet, D. & Milano, G. (2002) Prognostic value of tumoral thymidylate synthase and p53 in metastatic colorectal cancer patients receiving fluorouracil-based chemotherapy: phenotypic and genotypic analyses. J. Clin. Oncol. 20: 2832-2843.
104. Pullarkat, S. T., Stoehlmacher, J., Ghaderi, V., Xiong, Y. P., Ingles, S. A., Sherrod, A., Warren, R., Tsao-Wei, D., Groshen, S. & Lenz, H. J. (2001) Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J. 1: 65-70.
105. Villafranca, E., Okruzhnov, Y., Dominguez, M. A., Garcia-Foncillas, J., Azinovic, I., Martinez, E., Illarramendi, J. J., Arias, F., Martinez Monge, R., Salgado, E., Angeletti, S. & Brugarolas, A. (2001) Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J. Clin Oncol. 19: 1779-1786.
106. Marsh, S., McKay, J. A., Cassidy, J. & McLeod, H. L. (2001) Polymorphism in the thymidylate synthase promoter enhancer region in colorectal cancer. Int. J. Oncol. 19: 383-386.
107. Iacopetta, B., Grieu, F., Joseph, D. & Elsaleh, H. (2001) A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. Br. J. Cancer 85: 827-830.
108. Heijmans, B. T., Boer, J. M., Suchiman, H. E., Cornelisse, C. J., Westendorp, R. G., Kromhout, D., Feskens, E. J. & Slagboom, P. E. (2003) A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res. 63: 1249-1253.
109. Park, K. S., Mok, J. W. & Kim, J. C. (1999) The 677>T mutation in 5,10-methylenetetrahydrofolate reductase and colorectal cancer risk. Genet. Test. 3: 233-236.
110. Sachse, C., Smith, G., Wilkie, M. J., Barrett, J. H., Waxman, R., Sullivan, F., Forman, D., Bishop, D. T. & Wolf, C. R. (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23: 1839-1849.
111. Ulvik, A., Evensen, E. T., Lien, E. A., Hoff, G., Vollset, S. E., Majak, B. M. & Ueland, P. M. (2001) Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum. Am. J. Med. Genet. 101: 246-254.
112. Marugame, T., Tsuji, E., Inoue, H., Shinomiya, S., Kiyohara, C., Onuma, K., Hamada, H., Koga, H., Handa, K., Hayabuchi, H. & Kono, S. (2000) Methylenetetrahydrofolate reductase polymorphism and risk of colorectal adenomas. Cancer Lett. 151: 181-186.
113. Chen, J., Giovannucci, E., Hankinson, S. E., Ma, J., Willett, W. C., Spiegelman, D., Kelsey, K. T. & Hunter, D. J. (1998) A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma. Carcinogenesis 19: 2129-2132.