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Erschienen in: Breast Cancer Research and Treatment 3/2008

01.12.2008 | Epidemiology

Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer

verfasst von: Joanne Kotsopoulos, William W. Zhang, Shiyu Zhang, David McCready, Maureen Trudeau, Phil Zhang, Ping Sun, Steven A. Narod

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2008

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Abstract

Background An accumulating body of evidence suggests that there is an inverse relationship between the intake of folate (a water-soluble B-vitamin) and the risk of developing breast cancer. Individual variation in the genes involved in the transport of folate, or its metabolism, may affect risk, or may modify the association between folate and breast cancer risk. Methods We performed a case-control study to evaluate the association between common polymorphisms in six folate-related genes and the risk of breast cancer in 1,009 breast cancer patients and 907 healthy controls. Study subjects were genotyped for eight single nucleotide polymorphisms (SNPs) in these six genes. Results We observed no association between the MTHFR, RFC, MS and MTRR genotypes and the risk of breast cancer. Conclusion These data do not support the hypothesis that genetic variation in genes involved in the metabolism of folate are implicated in the etiology of breast cancer.
Literatur
1.
Zurück zum Zitat Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10(2):66–88PubMedCrossRef Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10(2):66–88PubMedCrossRef
2.
Zurück zum Zitat Wagner C (1995) Biochemical role of folate in cellular metabolism. In: Bailey LB (ed) Folate in health and disease. Marcel Dekker Inc, New York, pp 23–42 Wagner C (1995) Biochemical role of folate in cellular metabolism. In: Bailey LB (ed) Folate in health and disease. Marcel Dekker Inc, New York, pp 23–42
3.
Zurück zum Zitat Selhub J, Miller JW (1992) The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55(1):131–138PubMed Selhub J, Miller JW (1992) The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55(1):131–138PubMed
4.
Zurück zum Zitat Baylin SB et al (1998) Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 72:141–196PubMedCrossRef Baylin SB et al (1998) Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 72:141–196PubMedCrossRef
5.
6.
Zurück zum Zitat Duthie SJ (1999) Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 55(3):578–592PubMedCrossRef Duthie SJ (1999) Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 55(3):578–592PubMedCrossRef
7.
Zurück zum Zitat Kim YI (2004) Folate, colorectal carcinogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen 44(1):10–25PubMedCrossRef Kim YI (2004) Folate, colorectal carcinogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen 44(1):10–25PubMedCrossRef
8.
Zurück zum Zitat Zhang SM (2004) Role of vitamins in the risk, prevention, and treatment of breast cancer. Curr Opin Obstet Gynecol 16(1):19–25PubMedCrossRef Zhang SM (2004) Role of vitamins in the risk, prevention, and treatment of breast cancer. Curr Opin Obstet Gynecol 16(1):19–25PubMedCrossRef
9.
Zurück zum Zitat Eichholzer M et al (2001) Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Wkly 131(37–38):539–549PubMed Eichholzer M et al (2001) Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Wkly 131(37–38):539–549PubMed
10.
Zurück zum Zitat Lewis SJ et al (2006) Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst 98(22):1607–1622PubMedCrossRef Lewis SJ et al (2006) Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst 98(22):1607–1622PubMedCrossRef
11.
Zurück zum Zitat Zhang S et al (1999) A prospective study of folate intake and the risk of breast cancer. Jama 281(17):1632–1637PubMedCrossRef Zhang S et al (1999) A prospective study of folate intake and the risk of breast cancer. Jama 281(17):1632–1637PubMedCrossRef
12.
Zurück zum Zitat Rohan TE et al (2000) Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 92(3):266–269PubMedCrossRef Rohan TE et al (2000) Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 92(3):266–269PubMedCrossRef
13.
Zurück zum Zitat Sellers TA et al (2001) Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 12(4):420–428PubMedCrossRef Sellers TA et al (2001) Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 12(4):420–428PubMedCrossRef
14.
Zurück zum Zitat Shrubsole MJ et al (2001) Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 61(19):7136–7141PubMed Shrubsole MJ et al (2001) Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 61(19):7136–7141PubMed
15.
Zurück zum Zitat Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159(5):423–443PubMedCrossRef Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159(5):423–443PubMedCrossRef
16.
Zurück zum Zitat Ulrich CM, Robien K, Sparks R (2002) Pharmacogenetics and folate metabolism – a promising direction. Pharmacogenomics 3(3):299–313PubMedCrossRef Ulrich CM, Robien K, Sparks R (2002) Pharmacogenetics and folate metabolism – a promising direction. Pharmacogenomics 3(3):299–313PubMedCrossRef
17.
Zurück zum Zitat Justenhoven C et al (2005) One-carbon metabolism and breast cancer risk: no association of MTHFR, MTR, and TYMS polymorphisms in the GENICA study from Germany. Cancer Epidemiol Biomarkers Prev 14(12):3015–3018PubMedCrossRef Justenhoven C et al (2005) One-carbon metabolism and breast cancer risk: no association of MTHFR, MTR, and TYMS polymorphisms in the GENICA study from Germany. Cancer Epidemiol Biomarkers Prev 14(12):3015–3018PubMedCrossRef
18.
Zurück zum Zitat Zhai X et al (2006) Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis. BMC Cancer 6:138PubMedCrossRef Zhai X et al (2006) Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis. BMC Cancer 6:138PubMedCrossRef
19.
Zurück zum Zitat Xu WH et al (2007) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 16(2):281–287PubMedCrossRef Xu WH et al (2007) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 16(2):281–287PubMedCrossRef
20.
Zurück zum Zitat Zintzaras E (2006) Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a meta-analysis. Clin Genet 69(4):327–336PubMedCrossRef Zintzaras E (2006) Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a meta-analysis. Clin Genet 69(4):327–336PubMedCrossRef
21.
Zurück zum Zitat Mason JB, Rosenberg IH (1994) Intestinal absorption of folate. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven, New York Mason JB, Rosenberg IH (1994) Intestinal absorption of folate. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven, New York
22.
Zurück zum Zitat Shane B (1995) Folate chemistry and metabolism. In: Bailey LB (ed) Folate in health and disease. Marcel Dekker Inc, New York, pp 1–22 Shane B (1995) Folate chemistry and metabolism. In: Bailey LB (ed) Folate in health and disease. Marcel Dekker Inc, New York, pp 1–22
23.
Zurück zum Zitat Chango A et al (2000) A polymorphism (80G→A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Mol Genet Metab 70(4):310–315PubMedCrossRef Chango A et al (2000) A polymorphism (80G→A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Mol Genet Metab 70(4):310–315PubMedCrossRef
24.
Zurück zum Zitat Schirch L, Peterson D (1980) Purification and properties of mitochondrial serine hydroxymethyltransferase. J Biol Chem 255(16):7801–7806PubMed Schirch L, Peterson D (1980) Purification and properties of mitochondrial serine hydroxymethyltransferase. J Biol Chem 255(16):7801–7806PubMed
25.
Zurück zum Zitat Schirch L (1982) Serine hydroxymethyltransferase. Adv Enzymol Relat Areas Mol Biol 53:83–112PubMedCrossRef Schirch L (1982) Serine hydroxymethyltransferase. Adv Enzymol Relat Areas Mol Biol 53:83–112PubMedCrossRef
26.
Zurück zum Zitat Heil SG et al (2001) Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab 73(2):164–172PubMedCrossRef Heil SG et al (2001) Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab 73(2):164–172PubMedCrossRef
27.
Zurück zum Zitat Frosst P et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113PubMedCrossRef Frosst P et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113PubMedCrossRef
28.
Zurück zum Zitat Weisberg I et al (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64(3):169–172PubMedCrossRef Weisberg I et al (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64(3):169–172PubMedCrossRef
29.
Zurück zum Zitat Sharp L et al (2002) Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR). Cancer Lett 181(1):65–71PubMedCrossRef Sharp L et al (2002) Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR). Cancer Lett 181(1):65–71PubMedCrossRef
30.
Zurück zum Zitat Le Marchand L et al (2004) MTHFR polymorphisms, diet, HRT, and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 13(12):2071–2077PubMed Le Marchand L et al (2004) MTHFR polymorphisms, diet, HRT, and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 13(12):2071–2077PubMed
31.
Zurück zum Zitat Campbell IG et al (2002) Methylenetetrahydrofolate reductase polymorphism and susceptibility to breast cancer. Breast Cancer Res 4(6):R14PubMedCrossRef Campbell IG et al (2002) Methylenetetrahydrofolate reductase polymorphism and susceptibility to breast cancer. Breast Cancer Res 4(6):R14PubMedCrossRef
32.
Zurück zum Zitat Gershoni-Baruch R et al (2000) Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. Eur J Cancer 36(18):2313–2316PubMedCrossRef Gershoni-Baruch R et al (2000) Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. Eur J Cancer 36(18):2313–2316PubMedCrossRef
33.
Zurück zum Zitat Rady PL et al (2002) Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A. Am J Med Genet 107(2):162–168PubMedCrossRef Rady PL et al (2002) Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A. Am J Med Genet 107(2):162–168PubMedCrossRef
34.
Zurück zum Zitat Leclerc D et al (1996) Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Hum Mol Genet 5(12):1867–1874PubMedCrossRef Leclerc D et al (1996) Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Hum Mol Genet 5(12):1867–1874PubMedCrossRef
35.
Zurück zum Zitat Harmon DL et al (1999) Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet Epidemiol 17(4):298–309PubMedCrossRef Harmon DL et al (1999) Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet Epidemiol 17(4):298–309PubMedCrossRef
36.
Zurück zum Zitat Pufulete M et al (2005) Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer. Br J Cancer 92(5):838–842PubMedCrossRef Pufulete M et al (2005) Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer. Br J Cancer 92(5):838–842PubMedCrossRef
37.
Zurück zum Zitat Wilson A et al (1999) A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab 67(4):317–323PubMedCrossRef Wilson A et al (1999) A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab 67(4):317–323PubMedCrossRef
38.
Zurück zum Zitat Gaughan DJ et al (2001) The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. Atherosclerosis 157(2):451–456PubMedCrossRef Gaughan DJ et al (2001) The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. Atherosclerosis 157(2):451–456PubMedCrossRef
39.
Zurück zum Zitat Geisel J et al (2001) Genetic defects as important factors for moderate hyperhomocysteinemia. Clin Chem Lab Med 39(8):698–704PubMedCrossRef Geisel J et al (2001) Genetic defects as important factors for moderate hyperhomocysteinemia. Clin Chem Lab Med 39(8):698–704PubMedCrossRef
40.
Zurück zum Zitat O’Leary VB et al (2002) MTRR and MTHFR polymorphism: link to Down syndrome? Am J Med Genet 107(2):151–155PubMedCrossRef O’Leary VB et al (2002) MTRR and MTHFR polymorphism: link to Down syndrome? Am J Med Genet 107(2):151–155PubMedCrossRef
41.
Zurück zum Zitat Kraus JP et al (1998) The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics 52(3):312–324PubMedCrossRef Kraus JP et al (1998) The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics 52(3):312–324PubMedCrossRef
42.
Zurück zum Zitat Shen M et al (2005) Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer 49(3):299–309PubMedCrossRef Shen M et al (2005) Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer 49(3):299–309PubMedCrossRef
43.
Zurück zum Zitat Shrubsole MJ et al (2004) MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 13(2):190–196PubMedCrossRef Shrubsole MJ et al (2004) MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 13(2):190–196PubMedCrossRef
Metadaten
Titel
Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer
verfasst von
Joanne Kotsopoulos
William W. Zhang
Shiyu Zhang
David McCready
Maureen Trudeau
Phil Zhang
Ping Sun
Steven A. Narod
Publikationsdatum
01.12.2008
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-008-9895-6

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