Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women.
ABSTRACT BACKGROUND: Although global hypomethylation of leukocyte DNA has been associated with an increased risk of several sites of cancer, including breast cancer, determinants of global methylation level among healthy individuals remain largely unexplored. Here, we examined whether postmenopausal endogenous sex hormones were associated with the global methylation level of leukocyte DNA. METHODS: A cross-sectional study was conducted using the control group of a breast cancer case-control study in Nagano, Japan. Subjects were postmenopausal women aged 55 years or over who provided blood samples. We measured global methylation level of peripheral blood leukocyte DNA by luminometric methylation assay; estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex-hormone binding globulin by immunoradiometric assay. A linear trend of association between methylation and hormone levels was evaluated by regression coefficients in a multivariable liner regression model. A total of 185 women were included in the analyses. RESULTS: Mean global methylation level (standard deviation) was 70.3% (3.1) and range was from 60.3% to 79.2%. Global methylation level decreased 0.27% per quartile category for estradiol and 0.39% per quartile category for estron while it increased 0.41% per quartile category for bioavailable estradiol. However, we found no statistically significant association of any sex hormone level measured in the present study with global methylation level of leukocyte DNA. CONCLUSIONS: Our findings suggest that endogenous sex hormones are not major determinantsof the global methylation level of leukocyte DNA.
Article: Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan.[show abstract] [hide abstract]
ABSTRACT: We investigated associations among intake of folate, vitamin B2, vitamin B6, vitamin B12, and polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes and breast cancer risk in a Japanese population. A hospital based, case-control study was conducted in Nagano Prefecture, Japan, in 388 pairs of patients with histologically confirmed invasive breast cancer and age- and area-matched controls selected from medical checkup examinees. Energy-adjusted intakes of folate and other B vitamins were derived from a validated food frequency questionnaire. Genotyping was completed for MTHFR (C677T and A1298T) and MTR (A2756G). Odds ratios and 95% confidence intervals were calculated by the conditional logistical regression model. Median dietary folate intake (microg/day) in the control group was 438.2 (interquartile range: 354.9-542.9). Neither dietary intake of folate, vitamin B2, vitamin B6, or vitamin B12 nor polymorphisms of MTHFR or MTR genes were significantly associated with breast cancer risk. Further, no significant interaction was found among nutrients, polymorphisms, and breast cancer risk. Associations of nutrients with breast cancer risk did not differ by hormone receptors status. We conclude that dietary intake of folate and related B vitamins and genotypes of MTHFR or MTR have no overall association with breast cancer risk in Japanese women.Nutrition and Cancer 01/2009; 61(4):447-56. · 2.78 Impact Factor