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Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan.
Carcinogenesis 2006; 27(11):2295-300C

Abstract

Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both are implicated in carcinogenesis. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate cancer-predisposing factor. To evaluate the C677T and A1298C functional polymorphisms in the MTHFR gene and their associations with breast cancer risk, as well as the potential modifying effect by plasma folate status on the MTHFR-associated risk, a hospital-based case-control study was conducted on a Taiwanese population consisting of 146 histologically confirmed incident breast cancer cases and their 285 age-matched controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping and RIA was used to measure the plasma folate. Statistical evaluations were performed using logistic regression analysis. The plasma folate level was inversely associated with breast cancer risk with an adjusted odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.26-1.05] observed among women who were in the highest plasma folate tertile. The MTHFR 677T and 1298C variant alleles were associated with decreased risk for breast cancer [adjusted ORs were 0.81 (95% CI: 0.54-1.21) and 0.57 (95% CI: 0.36-0.89) for 677CT + TT genotypes and 1298AC + CC genotypes, respectively]. Furthermore, compound heterozygote and homozygote variants (677CT + TT and 1298AC + CC) had greater reduced risk (adjusted OR: 0.11, 95% CI: 0.03-0.43) among women with lower plasma folate levels. These results provide support for the important role of folate metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how MTHFR combined genotypes exert their effect on cancer susceptibility.

Authors+Show Affiliations

Graduate Institute of Medical Sciences, National Defense Medical Center Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16777985

Citation

Chou, Yu-Ching, et al. "Genetic Polymorphisms of the Methylenetetrahydrofolate Reductase Gene, Plasma Folate Levels and Breast Cancer Susceptibility: a Case-control Study in Taiwan." Carcinogenesis, vol. 27, no. 11, 2006, pp. 2295-300.
Chou YC, Wu MH, Yu JC, et al. Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan. Carcinogenesis. 2006;27(11):2295-300.
Chou, Y. C., Wu, M. H., Yu, J. C., Lee, M. S., Yang, T., Shih, H. L., ... Sun, C. A. (2006). Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan. Carcinogenesis, 27(11), pp. 2295-300.
Chou YC, et al. Genetic Polymorphisms of the Methylenetetrahydrofolate Reductase Gene, Plasma Folate Levels and Breast Cancer Susceptibility: a Case-control Study in Taiwan. Carcinogenesis. 2006;27(11):2295-300. PubMed PMID: 16777985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan. AU - Chou,Yu-Ching, AU - Wu,Mei-Hsuan, AU - Yu,Jyh-Cherng, AU - Lee,Meei-Shyuan, AU - Yang,Tsan, AU - Shih,Hsiu-Lan, AU - Wu,Tsai-Yi, AU - Sun,Chien-An, Y1 - 2006/06/15/ PY - 2006/6/17/pubmed PY - 2006/12/27/medline PY - 2006/6/17/entrez SP - 2295 EP - 300 JF - Carcinogenesis JO - Carcinogenesis VL - 27 IS - 11 N2 - Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both are implicated in carcinogenesis. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate cancer-predisposing factor. To evaluate the C677T and A1298C functional polymorphisms in the MTHFR gene and their associations with breast cancer risk, as well as the potential modifying effect by plasma folate status on the MTHFR-associated risk, a hospital-based case-control study was conducted on a Taiwanese population consisting of 146 histologically confirmed incident breast cancer cases and their 285 age-matched controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping and RIA was used to measure the plasma folate. Statistical evaluations were performed using logistic regression analysis. The plasma folate level was inversely associated with breast cancer risk with an adjusted odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.26-1.05] observed among women who were in the highest plasma folate tertile. The MTHFR 677T and 1298C variant alleles were associated with decreased risk for breast cancer [adjusted ORs were 0.81 (95% CI: 0.54-1.21) and 0.57 (95% CI: 0.36-0.89) for 677CT + TT genotypes and 1298AC + CC genotypes, respectively]. Furthermore, compound heterozygote and homozygote variants (677CT + TT and 1298AC + CC) had greater reduced risk (adjusted OR: 0.11, 95% CI: 0.03-0.43) among women with lower plasma folate levels. These results provide support for the important role of folate metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how MTHFR combined genotypes exert their effect on cancer susceptibility. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/16777985/Genetic_polymorphisms_of_the_methylenetetrahydrofolate_reductase_gene_plasma_folate_levels_and_breast_cancer_susceptibility:_a_case_control_study_in_Taiwan_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgl108 DB - PRIME DP - Unbound Medicine ER -