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One-carbon metabolism-related gene polymorphisms and risk of breast cancer.
Carcinogenesis. 2008 Feb; 29(2):356-62.C

Abstract

Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women.

Authors+Show Affiliations

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. suzuki@aichi-cc.jpNo affiliation info availableNo 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

18174236

Citation

Suzuki, Takeshi, et al. "One-carbon Metabolism-related Gene Polymorphisms and Risk of Breast Cancer." Carcinogenesis, vol. 29, no. 2, 2008, pp. 356-62.
Suzuki T, Matsuo K, Hirose K, et al. One-carbon metabolism-related gene polymorphisms and risk of breast cancer. Carcinogenesis. 2008;29(2):356-62.
Suzuki, T., Matsuo, K., Hirose, K., Hiraki, A., Kawase, T., Watanabe, M., Yamashita, T., Iwata, H., & Tajima, K. (2008). One-carbon metabolism-related gene polymorphisms and risk of breast cancer. Carcinogenesis, 29(2), 356-62. https://doi.org/10.1093/carcin/bgm295
Suzuki T, et al. One-carbon Metabolism-related Gene Polymorphisms and Risk of Breast Cancer. Carcinogenesis. 2008;29(2):356-62. PubMed PMID: 18174236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - One-carbon metabolism-related gene polymorphisms and risk of breast cancer. AU - Suzuki,Takeshi, AU - Matsuo,Keitaro, AU - Hirose,Kaoru, AU - Hiraki,Akio, AU - Kawase,Takakazu, AU - Watanabe,Miki, AU - Yamashita,Toshinari, AU - Iwata,Hiroji, AU - Tajima,Kazuo, Y1 - 2008/01/03/ PY - 2008/1/5/pubmed PY - 2008/3/26/medline PY - 2008/1/5/entrez SP - 356 EP - 62 JF - Carcinogenesis JO - Carcinogenesis VL - 29 IS - 2 N2 - Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/18174236/One_carbon_metabolism_related_gene_polymorphisms_and_risk_of_breast_cancer_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgm295 DB - PRIME DP - Unbound Medicine ER -