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

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 (μg/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.

ACKNOWLEDGMENTS

Grant support was from Grant-in-Aid for Research on Risk of Chemical Substances from the Ministry of Health, Labour and Welfare of Japan, and Grants-in-Aid for Scientific Research on Priority Areas (17015049) and for Young Scientists (B) (17790378 and 19790415) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and Japan Society for the Promotion of Science.

Notes

^a Mean ± SD. P value by t-test.

^b No. (%). P value by Cochran–Mantel–Haenszel test with matched-pair strata.

^a Abbreviations are as follows: OR, odds ratio; CI, confidence interval; BMI, body mass index.

^b Energy-adjusted intakes are categorized among controls by tertiles of folate, vitamin B2, vitamin B6, and vitamin B12.

^c Adjusted by BMI (< 21, 21– < 24, 24– < 27, ≥ 27 kg/m2), education (junior high school or less, high school, junior college or technical school, university or more), smoking status (never, ever), alcohol consumption (never, occasional, regular), age at menarche (< 12, 12, 13, 14, ≥ 15 yr), age at first live birth in parous women (nulliparous, < 25, 25– < 27, 27– < 29, ≥ 29 yr), menstruation status (no, yes), breast feeding (nulliparous, parous without breast feeding, parous with breast feeding), number of live births (nulliparous, 1, 2, ≥ 3), and moderate physical activity in the preceding 5 yr (no, yes).

^a Abbreviations are as follows: OR, odds ratio; CI, confidence interval; ER, estrogen receptor, PR, progesterone receptor; BMI, body mass index.

^b Energy-adjusted intakes are categorized among controls by tertiles of folate, vitamin B2, vitamin B6, and vitamin B12.

^c ER–, PR– = ER negative and PR negative; ER+, PR– = ER positive and PR negative; ER+, PR+ = ER positive and PR positive.

^d Odds ratios are adjusted by BMI (< 21, 21– < 24, 24– < 27, ≥ 27 kg/m²), education (junior high school or less, high school, junior college or technical school, university or more), smoking status (never, ever), alcohol consumption (never, occasional, regular), age at menarche (< 12, 12, 13, 14, ≥ 15 yr), age at first live birth in parous women (nulliparous, < 25, 25– < 27, 27– < 29, ≥ 29 yr), menstruation status (no, yes), breast feeding (nulliparous, parous without breast feeding, parous with breast feeding), number of living births (nulliparous, 1, 2, ≥ 3), and moderate physical activity in the preceding 5 yr (no, yes).

^a Abbreviations are as follows: OR, odds ratio; CI, confidence interval; MTHFR, 5,10-methylenetetrahydrofolate reductase; MTR, methionine synthase; BMI, body mass index.

^b Adjusted by BMI (< 21, 21– < 24, 24– < 27, ≥ 27 kg/m²), education (junior high school or less, high school, junior college or technical school, university or more), smoking status (never, ever), alcohol consumption (never, occasional, regular), age at menarche (< 12, 12, 13, 14, ≥ 15 yr), age at the first live birth in parous women (nulliparous, < 25, 25– < 27, 27– < 29, ≥ 29 yr), menstruation status (no, yes), breast feeding (nulliparous, parous without breast feeding, parous with breast feeding), number of live births (nulliparous, 1, 2, ≥ 3), and moderate physical activity in the preceding 5 yr (no, yes).

^a Abbreviations are as follows: OR, odds ratio; CI, confidence interval; MTHFR, 5,10-methylenetetrahydrofolate reductase; MTR, methionine synthase; BMI, body mass index.

^b Calorie-adjusted intakes are categorized among controls by tertiles of folate, vitamin B2, vitamin B6, and vitamin B12.

^c Odds ratios are adjusted by BMI (< 21, 21– < 24, 24– < 27, ≥ 27 kg/m²), education (junior high school or less, high school, junior college or technical school, university or more), smoking status (never, ever), alcohol consumption (never, occasional, regular), age at menarche (< 12, 12, 13, 14, ≥ 15 yr), age at first live birth in parous women (nulliparous, < 25, 25– < 27, 27– < 29, ≥ 29 yr), menstruation status (no, yes), breast feeding (nulliparous, parous without breast feeding, parous with breast feeding), number of live births (nulliparous, 1, 2, ≥ 3), and moderate physical activity in the preceding 5 yr (no, yes).