SPECIAL NOTICE
B -- Procurement of professional services for the measurement of genomic instability in pre-diagnostic blood samples among those with long and short telomeres in the Shanghai Women�s Health Study (CAS: 20136)
- Notice Date
- 8/10/2021 7:12:25 AM
- Notice Type
- Special Notice
- NAICS
- 541990
— All Other Professional, Scientific, and Technical Services
- Contracting Office
- NIH National Cancer Institute Rockville MD 20850 USA
- ZIP Code
- 20850
- Solicitation Number
- 75N91021Q00217
- Response Due
- 8/17/2021 12:00:00 PM
- Archive Date
- 09/01/2021
- Point of Contact
- Megan Kisamore, Phone: 2402765261
- E-Mail Address
-
megan.kisamore@nih.gov
(megan.kisamore@nih.gov)
- Description
- 1.0�� �DESCRIPTION The U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology & Genetics (DCEG), Occupational and Environmental Epidemiology Branch (OEEB) plans to procure services, on a sole source basis, from The University of Utah, 201 Presidents CIR, Salt Lake City, Utah 84112-9049. The response close date of the notice for this requirement is in accordance with FAR 5.203(b). This acquisition will be processed under FAR Part 12 - Acquisition for Commercial Items and will be made pursuant to the authority in FAR Part 13.106-1(b)(1)(i); and is exempt from the requirements of FAR Part 6. The North American Industry Classification System code is 541990 and the small business size standard is $16.5 million It has been determined there are no opportunities to acquire green products or services for this procurement.� 2.0�� �BACKGROUND Telomeres are repetitive hexameric (TTAGGG)n sequences at the ends of linear chromosomes that biologically interact with various DNA-binding proteins to form the protective shelterin complex. This specialized structure acts as a vanguard against genomic decay from progressive age, endogenous factors, and environmental exposures. Telomeres shorten approximately 50-200 bp with each round of mitosis (depending on various factors such as age) due to limitations in the synthesis of lagging strand DNA. As such, telomeres are often regarded as a �molecular clock� reflective of replicative history and potential of a cell.� Exposure to genotoxic environmental, occupational, and lifestyle factors that promote inflammation and oxidative stress contribute to telomere decay. In human studies, altered leukocyte telomere length (LTL) was associated with exposure to outdoor air pollution, benzene, toluene and black carbon, persistent organic pollutants (POPs), and arsenic in water amongst others. Additionally, associations were found with exposure to occupational welding and metal-rich fumes, lead, ionizing radiation, polycyclic aromatic hydrocarbons (PAHs), N-nitrosamine, and pesticides, as well as smoking and early life secondhand smoke.� Human somatic cells can only divide a maximum number of times before critically eroded telomeres trigger cellular replicative senescence; a threshold known as the Hayflick limit. Cells that evade replicative senescence through genomic abnormalities that promote growth, such as inactivation of a critical cell cycle checkpoint gene (i.e., p53), continue to divide until extensive apoptosis is triggered by critically short telomeres (~12.8 telomeric repeats). The rare cells that survive this crisis are naturally selected to be capable of maintaining telomere length through activation of telomerase (TERT) expression via accumulation of chromosomal abnormalities, which can confer unlimited replicative potential to the cell. Truncated telomeres are common characteristics of early tumors; however, elongation of telomeres can occur with cancer progression.� These observations have created a traditional expectation that shorter telomeres are detrimental with respect to cancer development; however, the relationship between LTL and cancer risk in epidemiologic studies is complex. LTL is generally accepted as a proxy in surrogate tissue for key biological processes in the target tissue of interest. �In prospective studies, shorter LTL was associated with increased risk of bladder, esophageal and overall cancer; longer LTL was associated with increased risk of non-Hodgkin lymphoma and melanoma (marginally non-significant); and findings were non-significant or inconsistent for other sites including but not limited to breast, endometrial, and colorectal. Most notably, consistent and robust associations were found between longer LTL in pre-diagnostic blood samples and increased lung cancer risk in several prospective studies of lung cancer. Using GWAS data, a Mendelian Randomization analysis of 35 cancer-sites found that genetically longer telomeres were associated with increased risk of lung adenocarcinoma, amongst others. Another study found a positive association for lung adenocarcinoma but inverse association for squamous cell carcinoma. Additionally, a polygenic risk score that predicts longer LTL that was derived from 7 genetic variants confirmed the positive association with lung cancer. These key lung cancer findings present a paradox in the traditional expectations of telomere dynamics in cancer development. How could longer telomeres, generally reflective of less advanced age and less genomic decay, be associated with increased risk of developing lung cancer? To explain this phenomenon, it was posited that longer LTL may reflect or lead to delayed senescence of pre-cancerous cells, which allows them to accumulate somatic genomic abnormalities that potentially drive carcinogenesis and cancer progression. Later on, Aviv et al. (2017) further posited that a series of LTL-independent mutational hits (1st hit) at the stem-cell level generates a clone with replicative advantage and subsequently, a series of additional LTL-related mutational hits (2nd hit) transforms the expanding clone into cancer. However, no human studies have investigated these explanations. Therefore, consideration was given to evaluating different forms of genomic instability in relation to LTL and lung cancer risk.� Alu retroelements are repetitive mobile DNA sequences enriched with CpG sites that are ubiquitous throughout the human genome that can be considered a source of genomic instability . With over one million copies, Alu retroelements compose nearly 11% of the genome and are a major source of genetic copy-number aberrations and variations. The �young� AluY family is considered the most active form, can multiply, insert (�jump�) into different genomic locations, and increase in copy-number throughout the genome. This Alu activity can alter gene expression, modify epigenetic regulation of crucial genes, and disrupt genomic architecture. Alu repeats have been linked to various cancers and mortality in a few preliminary studies. Alu repeats were found to co-localize with GWAS hits related to some cancers (that may or may not be causal for disease). Further, DNA-damaging agents that cause strand breaks have been found to promote Alu jumping.� Double-stranded (ds) DNA breaks are a substantial source of genomic instability that involves chemical severing of the phosphate backbone of DNA. These abnormalities can occur due to endogenous factors such as defects in DNA replication and repair mechanisms, oxidative stress/damage from environmental exposures, and ionizing radiation. DNA breaks are well-established risk factors for various cancers, as they can trigger untimely DNA repair, chromosomal fusions and rearrangements. For instance, variants in the XRCC family of genes which are responsible for dsDNA break repair, have been found to be associated with increased lung cancer risk.� Mitochondria are key organelles responsible for aerobic respiration, cellular apoptosis, and production of reactive oxygen species (ROS). Abnormalities in mtDNA including copy number variations, lesions, methylation levels, deletions and mutations have been implicated in aging and chronic disease development. Oxidative stress from endogenous processes and induced by environmental exposures can potentially induce mtDNA breaks. The ~16.5 kbp mtDNA genome is situated close to ROS production sites and are susceptible to oxidative stress induced damage, which is worsened by the limited DNA repair mechanisms and lack of protective histone-DNA coiling. This is evident in that the frequency of mtDNA mutations is nearly 50-fold that of nuclear genomic DNA. Mitochondrial function and telomere length are biologically interrelated; when mitochondrial dysfunction occurs with concurrent ROS generation, the susceptibility of telomeres to oxidative damage can lead to accelerated erosion. 2.1�� �OBJECTIVE To investigate the role of LTL and markers of genomic instability (i.e., global Alu retrotransposon copy-number, global double-stranded DNA breaks across the genome located in Alu retrotransposons and in ribosomal DNA sequences, and double-stranded mitochondrial DNA breaks) in the etiology of lung cancer among never smokers, the U.S Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology & Genetics (DCEG) / Occupational and Environmental Epidemiology Branch (OEEB) is conducting a study of lung cancer in the Shanghai Women�s Health Study (SWHS). The Contractor shall conduct qPCR assays on DNA samples from this study.� 3.0�� �SCOPE The Contractor shall provide all personnel, labor, facilities, materials and equipment necessary to perform the required tasks described in section 4 below. This purchase order includes services to provide measurements on a total of 1960 previously collected/extracted samples and DNA. The samples are divided into 955 lung cancer cases, 955 individually matched controls, and 50 quality controls samples, all of whom never smoked and are from the prospective Shanghai Women�s Health Study (SWHS). All data shall be coded and shall not contain any personally identifiable information (PII). The Contractor shall measure the following, using qPCR methods: LTL and markers of genomic instability including global Alu retrotransposon copy-number; global double-stranded DNA breaks across the genome located in Alu retrotransposons and in ribosomal DNA sequences; and double-stranded mitochondrial DNA breaks in blood samples collected before lung cancer diagnosis. The cost of shipping samples to the Contractor�s facility is not included in this purchase order. NCI shall ship the samples to the Contractor in one shipment via the NIH shipping service. 4.0�� �PURCHASE ORDER REQUIREMENTS The Contractor shall perform the following tasks:� 4.1�� �Receive the samples shipment from NCI. The Contractor shall store the samples at </= -70C until they are defrosted and assayed. 4.2�� �Measure LTL on 1960 DNA samples, inclusive of 50 QC, using qPCR. 4.3�� �Measure Alu retrotransposon copy number on 1960 DNA samples, inclusive of 50 QC, using qPCR. 4.4�� �Measure global double stranded breaks in Alu sequences on 1960 DNA samples, inclusive of 50 QC, using qPCR. 4.5�� �Measure global double stranded breaks in rDNA sequences on 1960 DNA samples, inclusive of 50 QC, using qPCR. 4.6�� �Send the raw (in Biorad MyiQ system software format) and curated qPCR data (in MS Excel format) from all assays to the NCI. 4.7�� �The Contractor shall coordinate and participate in biweekly telephone calls with the NCI technical point of contact (TPOC) to discuss the number of samples processed. 5.0�� �TYPE OF ORDER This is a firm fixed price purchase order.� 6.0�� �NON-SEVERABLE SERVICES The services specified in each contract line item (CLIN) have been determined to be non-severable services - a specific undertaking or entire job with a defined end product of value to the Government. 7.0�� �PERIOD OF PERFORMANCE The anticipated period of performance shall be 12 months from the date of award.� � 8.0�� �PLACE OF PERFORMANCE All services shall be performed at the Contractor�s facility. 9.0�� �REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE All written deliverables shall be sent electronically to the NCI Technical Point of Contact (TPOC), TBD at award, in a Microsoft compatible format, such as Microsoft Excel or text file, and Biorad MyiQ system software unless approved by the TPOC in accordance with the following deliverable schedule: DELIVERABLE� /� �DELIVERABLE DESCRIPTION / FORMAT REQUIREMENTS� /� DUE DATE #1 (Task 4.2):�Measured LTL on 1960 DNA samples (inclusive of 50 QC) using qPCR in raw (Biorad MyiQ system software format) and curated qPCR data (in MS Excel format); Due�(30) business days prior to purchase order expiration date.� #2 (Task 4.3):�Measured Alu retrotransposon copy number on 1960 DNA samples (inclusive of 50 QC) using qPCR in raw (Biorad MyiQ system software format) and curated qPCR data (in MS Excel format); Due�(30) business days prior to purchase order expiration date. #3 (Task 4.4):�Measured global double stranded breaks in Alu sequences (inclusive of 50 QC) using qPCR in raw (Biorad MyiQ system software format) and curated qPCR data (in MS Excel format); Due�(30) business days prior to purchase order expiration date. #4 (Task 4.5):�Measured global double stranded breaks in rDNA sequences (inclusive of 50 QC) using qPCR in raw (Biorad MyiQ system software format) and curated qPCR data (in MS Excel format); Due�(30) business days prior to purchase order expiration date. 10.0�� �UNIQUE QUALIFICATIONS OF THE CONTRACTOR The University of Utah has developed assays to measure genomic instability, including telomere length, global Alu retrotransposon copy-number, global double-stranded DNA breaks across the genome located in Alu retrotransposons and in ribosomal DNA sequences, and double-stranded mitochondrial DNA breaks. The University of Utah previously conducted assays of telomere length in peripheral white blood cell samples from the early stage of the same study (HHSN261201700060A and HHSN261200900496P). �Further, this laboratory has previously analyzed DNA samples from NCI studies for white blood cell DNA genomic biomarkers including ALU retroelement copy number and telomere length (HHSN261201700060A), and mtDNA assays (75N91019P00678). The same techniques will be used to the current requested assays, but on additional samples from the same extended project. �It is critically important to use the same laboratory for the current requirement to ensure scientific comparability of the new results with previous results from the studies previously conducted. Procuring the services through another source would result in of substantial inter-laboratory variation. The goal of this analysis is to benefit the U.S. government and the public by providing new information about the mechanism of exposure to chemicals causing cancers, which is an important public health concern. 11.0�� �SUBMISSION INSTRUCTIONS This notice is not a request for competitive quotations. However, if any interested party believes it can meet the above requirements, it may submit a proposal or quote for the Government to consider. The response and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform the requirement. �All responses and questions must be sent via email to Contracting Officer, Megan Kisamore, at megan.kisamore@nih.gov by no later than 3:00 PM EST, on Tuesday, August 17, 2021 (8/17/21). A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. In order to receive an award, Contractors must be registered and have valid certification through SAM.gov. Reference: 75N91021Q00217 on all correspondence.
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