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Prediagnostic Plasma Pyridoxal 5 -Phosphate (Vitamin B6) Levels

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Prediagnostic Plasma Pyridoxal 5 -Phosphate (Vitamin B6) Levels Published OnlineFirst August 9, 2012; DOI: 10.1158/1055-9965.EPI-12-0717-T Cancer Epidemiology, Research Article Biomarkers & Prevention Prediagnostic Plasma Pyridoxal 50-Phosphate (Vitamin B6) Levels and Invasive Breast Carcinoma Risk: The Multiethnic Cohort Galina Lurie1, Lynne R. Wilkens1, Yurii B. Shvetsov1, Nicholas J. Ollberding2, Adrian A. Franke1, Brian E. Henderson3, Laurence N. Kolonel1, and Marc T. Goodman1 Abstract 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-50-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 ¼ 0.02). The association seemed to be limited in cases with hormone receptor-positive tumors (P for heterogeneity ¼ 0.04); and remained unchanged in the analysis restricted to women with blood samples collected more than one year before cancer diagnosis (OR ¼ 0.69; CI: 0.48–0.99; P for trend ¼ 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; 21(11); 1942–8. Ó2012 AACR. Introduction metabolism, a sequence of biochemical processes that Identification of molecular mechanisms underlying enrich the cellular supply of methyl groups for DNA breast carcinogenesis is fundamental to the prevention synthesis, repair, and methylation (5). Apart from its role of breast cancer, the most common malignancy among as a coenzyme, vitamin B6 might affect carcinogenesis women (1). Although, many of the accepted breast cancer directly through inhibition of cell proliferation, oxidative risk factors, such as age at menarche, parity, age at first stress, angiogenesis, and enhanced immune function full-term pregnancy, and age at menopause are difficult to (reviewed in ref. 6). modify, diet is a potentially modifiable factor. However, Results from studies of the association of dietary vita- besides alcohol intake, no association of diet with post- min B6 intake (7–17) or circulating PLP levels (18–20) with menopausal breast cancer risk has been established (2). breast cancer risk are inconsistent. A randomized trial of Pyridoxal 50-phosphate (PLP), the active form of vita- combined folic acid, vitamin B6, and vitamin B12 reported significantly reduced breast cancer risk among women in min B6 (3), serves as a cofactor in more than 100 enzymatic reactions (4). Vitamin B6 is involved in one-carbon the treatment arm of older ( 65 years old) but not younger women (21). We investigated prediagnostic plasma levels of PLP in relation to invasive breast cancer risk among 1 Authors' Affiliations: University of Hawaii Cancer Center, Honolulu, postmenopausal women in the multiethnic cohort (MEC) Hawaii; 2Department of Health Studies, University of Chicago, Chicago, Illinois; and 3Department of Preventive Medicine, Keck School of Medicine, study. University of Southern California, Los Angeles, California Corresponding Author: Galina Lurie, Cancer Research Center of Hawaii, 1236 Lauhala Street, Room 502E, Honolulu, HI 96813. Phone: 808-564- Materials and Methods 5981; Fax: 808-586-2982; E-mail: [email protected] Study design and population doi: 10.1158/1055-9965.EPI-12-0717-T This case–control study was nested within the bio- Ó2012 American Association for Cancer Research. specimen subcohort of the MEC, a large prospective 1942 Cancer Epidemiol Biomarkers Prev; 21(11) November 2012 Downloaded from cebp.aacrjournals.org on September 26, 2021. © 2012 American Association for Cancer Research. Published OnlineFirst August 9, 2012; DOI: 10.1158/1055-9965.EPI-12-0717-T Plasma Vitamin B6 Levels and Breast Cancer Risk study of residents of Hawaii and Southern California, hormones at blood draw (none; current use of estrogen, which included 118,441 women (22). The population- progesterone, or combination of both). A total of 706 based sampling frames for the MEC included rolls from postmenopausal breast cancer cases and 706 matched drivers’ licenses, voters’ registration, and the Health Care controls were available for analysis. Tumor estrogen Financing Administration and was targeted to 5 ethnic receptor (ER) and progesterone receptor (PR) status was groups: African-American, Hawaiian, Japanese, Latino, available for 617 (87%) and 597 (85%) of the cases, and whites. At cohort entry, participants completed a respectively. self-administered, 26-page baseline questionnaire that included queries on demographic characteristics, anthro- Laboratory analyses pometry, medical history, family history of cancer, repro- Plasma samples were analyzed in the Analytical Bio- ductive and menstrual history, cancer risk factors, and chemistry laboratory of the University of Hawaii Cancer detailed questions on diet. The MEC biospecimen sub- Center (A.A. Franke, director) by laboratory personnel cohort was established from 1996 through 2006, with the blinded to the case–control status of the samples. The majority of recruitment occurring after 2001. All surviving PLP assay was based on the method of Rybak and cohort members still residing in the catchment area were Pfeiffer (23). Briefly, 150 mL freshly thawed plasma was m 2 recontacted and asked to provide biologic specimens, mixed for 5 minutes with 10 Laqueous H2-pyridoxal- including blood samples. Blood samples were drawn at 50-phosphate (internal standard, donated by Stephen a clinical laboratory or at the participants’ homes and P. Coburn, Purdue University, Fort Wayne, IN) and were kept refrigerated and protected from light until 50 mL 10% aqueous metaphosphoric acid (Sigma). After m processed on average within 3 hours of collection. After shaking with 200 LCH2Cl2, the supernatant aqueous centrifugation, blood components were aliquoted into layer was transferred into 350 mL round-bottom plates 0.5-mL cryovials and stored in the vapor phase of liquid (MicroLiter Analytical Supplies) and 20 mL of the aque- nitrogen (À150C). A total of 36,458 female cohort mem- ous layer were injected into the liquid chromatography/ bers contributed to the biorepository from which the tandem mass spectrometry (LC/MS-MS) system (model cases and controls were selected for the present study. Accela and TSQ-Ultra from Thermo Scientific Inc.). Although, the participants in the biospecimen subcohort PLP was separated on an Ascentis Express C18 column were slightly more educated (mean 13.6 years vs. 12.7 (150 mm  3.0 mm; 2.7 mm; Supelco Inc.) and a 0.2 mm years), were more likely to be nonsmokers (13% vs. 17%), prefilter cartridge (2.1 mm i.d., ThermoFisher) at a flow and had a family history of cancer (46% vs. 42%) than rate of 0.6 mL/min with the following linear mobile nonparticipants, they were similar in relation to other phase gradient consisting of 5% aqueous acetic acid (A) exposures and were generally representative of all cohort and 0.1% formic acid in acetonitrile (B): %B ¼ 4% for members. 1 minute then to 95% in 2 minutes, held at 95% for The study protocol was approved by the Institutional 1 minute and changed to 4% in 0.1 minute followed by Review Boards of the University of Hawaii and the equilibration for 4 minutes. Quantitation was conducted University of Southern California, and all participants by tandem mass spectrometry after positive electrospray signed informed consent. ionization in selected reaction monitoring mode by scanning the transitions m/z 248.0 to 150.1 (at 18 eV) Case ascertainment and control selection and m/z 229.9 (at 14 eV) for PLP and m/z 250.0 to 152.0 Linkages of the cohort to the Surveillance, Epidemio- (at 18 eV) for deuterated PLP (internal standard). Instru- logy, and End Results cancer registries in Hawaii and ment settings were as follows: spray voltage, 4,000 V; California are conducted annually to identify incident sheath gas, nitrogen; sheath gas pressure, 45 arbitrary breast cancer cases diagnosed during the follow-up peri- units; ion transfer capillary temperature, 350C. External od. Linkages to state death files and the National Death calibration was conducted with aqueous solutions Index are conducted to identify deaths. Postmenopausal of authentic standards (Sigma) in the range 5 to 1,000 women participating in the biospecimen repository, who nmol/L, and stock concentrations were determined by were diagnosed with primary invasive breast carcinoma absorbance readings (e ¼ 5,070 at 388 nm in water). before the most recent tumor registry linkage (December On the basis of a total of 47 duplicate and 23 triplet 31, 2010) and provided blood
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