Prediagnostic Plasma Pyridoxal 5 '-Phosphate (Vitamin B6) Levels and Invasive Breast Carcinoma Risk: The Multiethnic Cohort

2Department of Health Studies, University of Chicago, Chicago, Illinois
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 08/2012; 21(11). DOI: 10.1158/1055-9965.EPI-12-0717-T
Source: PubMed


BACKGROUND: Evidence from experimental and epidemiologic studies suggests that vitamin B6 may reduce the risk of breast cancer.METHODS: We examined the association of prediagnostic plasma concentrations of pyridoxal-5'-phosphate (PLP), an active form of vitamin B6, with postmenopausal breast cancer risk in a case-control study nested in the multiethnic cohort in Hawaii and Southern California, including 706 cases and 706 controls matched on date of birth, ethnicity, study site, date of blood draw, time of blood draw, hours of fasting before blood draw, and use of menopausal hormones. OR and 95% confidence intervals (CI) were calculated using conditional logistic regression models.RESULTS: Women with plasma PLP concentrations in the highest quartile had a 30% reduced risk of invasive breast cancer (CI: 0.50-0.98) as compared with the women in the lowest PLP quartile (P for trend = 0.02). The association seemed to be limited in cases with hormone receptor-positive tumors (P for heterogeneity = 0.04); and remained unchanged in the analysis restricted to women with blood samples collected more than one year before cancer diagnosis (OR = 0.69; CI: 0.48-0.99; P for trend = 0.03).CONCLUSIONS: These data suggest that higher circulating levels of vitamin B6 are associated with a reduced risk of invasive postmenopausal breast cancer.Impact: These results, in combination with information from two other prospective studies, suggest a role for vitamin B6 in the prevention of postmenopausal breast cancer. Additional studies are needed to further investigate potential heterogeneity of the vitamin B6 association with breast cancer risk by tumor hormone receptor status. Cancer Epidemiol Biomarkers Prev; 1-7. ©2012 AACR.

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    • "P ¼ 0.01, I 2 ¼ 0.00%). For dose–response analysis, data from three studies (Zhang et al, 2003; Lin et al, 2008; Lurie et al, 2012) were used, including 2266 breast cancer cases. We found no evidence of statistically significant departure from linearity (P ¼ 0.85). "
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    ABSTRACT: Background: Epidemiological studies evaluating the association of vitamin B6, vitamin B12 and methionine with breast cancer risk have produced inconsistent results. Methods: Pertinent studies were identified by a search in PubMed and Web of Knowledge. Random-effect model was used. Dose–response relationship was assessed by restricted cubic spline. Results: The combined relative risk (95% confidence interval) of breast cancer for the highest vs lowest category of serum pyridoxal 5′-phosphate (PLP, active form of vitamin B6) levels and dietary methionine intake was 0.80 (0.66–0.98, P=0.03) and 0.94 (0.89–0.99, P=0.03), respectively, and the associations of breast cancer with higher serum PLP levels and dietary methionine intake were significant among post-menopausal women, but not among pre-menopausal women. The inverse association between breast cancer risk and dietary vitamin B6 intake, serum vitamin B12 levels and dietary vitamin B12 intake was not significant overall. Linear dose–response relationship was found, and the risk of breast cancer decreased by 23% (P<0.00) for every 100 pmol ml−1 increment in PLP levels and 4% (P=0.05) for every 1 g per day increment in dietary methionine intake, respectively. Conclusion: Serum PLP levels and methionine intake might be inversely associated with breast cancer risk, especially among postmenopausal women, which need to be confirmed.
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    ABSTRACT: This prospective cohort study that comprehensively examined effects of different B vitamins in an Asian population showed an inverse relationship between dietary intake of pyridoxine and hip fracture risk in elderly women. These findings suggest that maintaining sufficient pyridoxine intake may be beneficial in preserving bone health in postmenopausal women. Introduction B vitamins have recently been investigated for their possible roles in maintaining bone health. Incidence of osteoporotic hip fracture has been rising in Asia, but epidemiological data on dietary B vitamins and risk of osteoporotic fractures are sparse. We aimed to examine the association between dietary intakes of B vitamins (thiamin, riboflavin, niacin, pyridoxine, folate, and cobalamin) and hip fracture risk among elderly Chinese in Singapore. Methods The current study was conducted in the Singapore Chinese Health Study, which is a population-based cohort prospective study that enrolled a total of 63,257 men and women aged 45–74 years between 1993 and 1998. Dietary intakes of B vitamins were derived from a validated food frequency questionnaire and the Singapore Food Composition Database. Results After a mean follow-up period of 13.8 years, 1,630 hip fracture incident cases were identified. A statistically significant inverse relationship between dietary pyridoxine intake and hip fracture risk was observed among women (p for trend = 0.002) but not among men. Compared to women in the lowest quartile intake (0.37–0.61 mg/1,000 kcal/day), women in the highest quartile intake (0.78–1.76 mg/1,000 kcal/day) had a 22 % reduction in hip fracture risk (hazard ratio 0.78, 95 % confidence interval 0.66–0.93). Dietary intakes of the other B vitamins of interest were not related to hip fracture risk. Conclusions Our findings suggest that maintaining adequate intake of pyridoxine may prevent osteoporotic fractures among elderly women.
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    ABSTRACT: Pyridoxal-5'-phosphate (PLP), the bioactive form of vitamin B6, reportedly functions as a prosthetic group for >4% of classified enzymatic activities of the cell. It is therefore not surprising that alterations of vitamin B6 metabolism have been associated with multiple human diseases. As a striking example, mutations in the gene coding for antiquitin, an evolutionary old aldehyde dehydrogenase, result in pyridoxine-dependent seizures, owing to the accumulation of a metabolic intermediate that inactivates PLP. In addition, PLP is required for the catabolism of homocysteine by transsulfuration. Hence, reduced circulating levels of B6 vitamers (including PLP as well as its major precursor pyridoxine) are frequently paralleled by hyperhomocysteinemia, a condition that has been associated with an increased risk for multiple cardiovascular diseases. During the past 30 years, an intense wave of clinical investigation has attempted to dissect the putative links between vitamin B6 and cancer. Thus, high circulating levels of vitamin B6, as such or as they reflected reduced amounts of circulating homocysteine, have been associated with improved disease outcome in patients bearing a wide range of hematological and solid neoplasms. More recently, the proficiency of vitamin B6 metabolism has been shown to modulate the adaptive response of tumor cells to a plethora of physical and chemical stress conditions. Moreover, elevated levels of pyridoxal kinase (PDXK), the enzyme that converts pyridoxine and other vitamin B6 precursors into PLP, have been shown to constitute a good, therapy-independent prognostic marker in patients affected by non-small cell lung carcinoma (NSCLC). Here, we will discuss the clinical relevance of vitamin B6 metabolism as a prognostic factor in cancer patients.Oncogene advance online publication, 21 January 2013; doi:10.1038/onc.2012.623.
    Full-text · Article · Jan 2013 · Oncogene
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