National Cancer Institute, Research Contracts Branch, PSAS, 6120 Executive Blvd, EPS/Room 638, Bethesda, MD 20892-7227

B -- SPECIAL STUDIES AND ANALYSIS-(MEASUREMENT OF PHYTOESTROGENS AND ESTROGEN METABOLITIES IN URINE FROM THE ASIAN-AMERICAN BREAST CANCER STUDY.) SOL RFQ-NCI-80239 DUE 092598 POC Cynthia Brown, Purchasing Agent, 301-402-4509, Todd Cole, Contracting Officer COMBINED SYNOPSIS/SOLICITATION FOR SERVICES INVOLVING THE MEASUREMENT OF PHYTOESTROGENS AND ESTROGEN METABOLITES IN URINE FROM THE ASIAN-AMERICAN BREAST CANCER STUDY The National Cancer Institute (NCI) plans to procure the subject analytical services in accordance with the simplified acquisition procedures authorized in FAR Part 13. This announcement constitutes a combined synopsis/solicitation, and a separate written solicitation will not be issued. The solicitation includes all applicable provisions and clauses in effect through FAR FAC 97-05. The Standard Industrial Classification Code is 8733. However, this requirement is not set-aside for small businesses.A. BACKGROUND:Estrogen is viewed as playing a critical role in breast cancer, yet the precise mechanism of estrogen activity involved is not clear. In epidemiologic studies, hormone related factors such as early age at menarche, late age at menopause, and reproductive characteristics are well established risks for breast cancer, and serum and urinary estrogens show consistently higher levels in cases than controls. Internationally, breast cancer incidence varies widely, with differences in diet and patterns of estrogen metabolism and excretion suggested as responsible for the notably lower rates in Asian vs. Caucasian women. Serum estrogens are lower in Oriental women, and dietary intake of soy has been shown to lower the risk of breast cancer in some epidemiologic studies. A recently published report shows a strong inverse association between breast cancer and the urinary excretion of several isoflavonoids that are the primary phytoestrogens in soy. A number of mechanisms for the anticarcinogenic effect of phytoestrogens have been proposed including that they: are antiestrogenic, acting by competing with estradiol (E2) for estrogen-binding sites; influence activity of tyrosine kinases and growth factors; and may interfere with estrogen synthesis and metabolism. E2 is oxidized mainly via two mutually exclusive pathways: either at C-2 (and to a lesserextent at C-4) yielding the catechol metabolites, 2- and 4-hydroxyestrone (2- and 4OHE1), 2- and 4-hydroxyestradiol (2- and 4-OHE2), 2- and 4-methoxyestrone (2- and 4MeOE1), and 2- and 4-methoxyestradiol (2- and 4-MeOE2); or at the C-16 position, yielding 16 alpha-hydroxyestrone (16a-OHE1) and estriol. A low ratio of 2-OHE1/16 alpha-OHE1 has been seen in some studies of women with newly diagnosed breast cancer, yet others show high 2-OHE1 in breast cancer cases or women at high risk for the disease. The Hormone Studies Section of the National Cancer Institute's Division of Cancer Epidemiology and Genetics wishes to assess whether phytoestrogens and estrogen metabolites can be reproducibly measured in urine samples from Asian-American women, and whether the high laboratory throughput required for a large case-control study of breast cancer in this population is feasible. B. Requirements:(1). The Contractor shall obtain 45 urine samples identified by the NCI for the measurement of 10 phytoestrogens (equol, O-desmethylangolensin (ODMA), dihydrodaidzein, daidzein, genistein, glycitein, enterodiol, enterolactone, matairesinol and coumestrol) and 15 estrogens and their metabolites (Estrone (E1), Estradiol (E2), Estriol (E3), 16aOHE1, 2-OHE1, 2-OHE2, 4-OHE1, 4-OHE2, 2-MeOE1, 2-MeOE2, 4-MeOE1, 4 MeOE2), 16-ketoestradiol (16-ketoE2), 16-epiestriol (16-epiE3), and 17-epiestriol (17 epiE3) by gas chromatography-mass spectrometry (GC-MS). The Contractor shall also perform elisa assays to measure urinary creatinine. The contractor shall meet or better (a lower coefficient of variation (CV) is better) intra-assay CVs<=8% and inter-assay CVs<=15% for all phytoestrogen and estrogen metabolites. These CVs shall be based on blinded quality control samples. (2). A total of 45 urine samples selected from the case-control study of breast cancer in Asian-American women shall be sent to the Contractor's facility by MA Bioservices, a NCI contractor, in three batches predetermined by the NCI and to be analyzed in consecutive order. In order to assess reproducibility, the same fifteen samples shall be analyzed in each of the three batches, for a total of 45 GC-MS analyses. The measurement of urinary creatinine shall require a total of 45 elisa assays. The order of the batches and the order of samples within a batch shall be maintained by the Contractor. (3). The Contractor shall be provided with an EXCEL file of sample id's listed in specified order within each batch. The results shall be sent to NCI (Roni Falk, Health Statistician, Hormone Studies Section) by e-mail. (4). NCI is shipping to the contractor a 25 ml aliquot of urine which shall be stored at -70 degrees Celsius. Samples shall be thawed at 4 degrees Celsius. The Contractor shall use the same internal standards in every aliquot and for each batch and provide the date of completion for each sample. The Contractor shall indicate to the NCI when repeats are done. These data, linked to the sample id's shall be transmitted to the NCI in an EXCEL file. (5). All analyses shall becompleted within 3 months of receipt of the samples. (6). NCI shall retain the right to all data derived from this procurement. C. Provisions and Clauses:The solicitation incorporates the NCI REPRESENTATIONS, CERTIFICATIONS, AND OTHER STATEMENTS OF OFFERORS OR QUOTERS (SIMPLIFIED ACQUISITIONS). The award document will incorporate the requirements of the clause at FAR 52.213-4, TERMS AND CONDITIONS -- SIMPLIFIED ACQUISITIONS. Full text copies of these documents may be obtained from Cynthia Brown on (301) 402-4509 or by fax on (301) 402- 4513.D. TECHNICAL EVAUATION CRITERIA:The technical portion of quotations will receive paramount consideration in selecting a vendor. However, price will also be a significant factor in the event that two or more vendors are determined to be essentially equal following the evaluation of technical factors. In any event, the Government reserves the right to make award to the vendor whose offer provides the greatest overall value to the Government. Offers will be evaluated based on the following technical evaluation criteria:(1). Approach: (40% ) The Offeror shall describe the method used to measure the above mentioned phytoestrogens, urinary estrogens and estrogen metabolites, including specifying procedures to ensure quality control. (2). Experience and capability of Offeror: ( 45%) The Principal Investigator must have at least a Ph.D. in chemistry, nutrition or a related field. This individual must have knowledge of phytoestrogen metabolism as evidenced by peer-reviewed publications.The Offerer shall demonstrate that the proposed method of analysis for both the phytoestrogens and the estrogen metabolites meets the level of reproducibility described herein, namely that inter-assay CVs are at or below 15% and intra-assay CVs are at or below 8%. (3). Facilities and Equipment: (15%) The Offeror shall demonstrate their facilities and equipment are capable of high throughput required in order to efficiently analyze a large number of urines (approximately 400 specimens) from the study of breast cancer in Asian-American women. E. OFFERS: Offers must be submitted on an SF-18 that is signed by an authorized representative of the offeror and includes a completed "Schedule of Offered Supplies/Services." The offer price must include all materials, reagents, labor, facilities, and indirect costs. Offers must be accompanied by a completed and signed NCI REPRESENTATIONS, CERTIFICATIONS, AND OTHER STATEMENTS OF OFFERORS OR QUOTERS (SIMPLIFIED ACQUISITIONS). Offers must also be accompanied by materials demonstrating that the offer and offeror meet the foregoing requirements and evaluation criteria.Offers and related materials must be received in this office by 3:00 pm EST on September 25, 1998. No collect calls will be accepted. Please cite the solicitation number,RFQ-NCI-80239, on your offer. Posted 09/04/98 (W-SN246396). (0247)

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