Other Major Projects and Resources
Transplant and Dialysis Cancer Match
Cancer risk is substantially elevated among solid organ transplant recipients, who receive long term immunosuppressant medications to prevent organ rejection. Risk is also high among patients on dialysis for end-stage renal disease. To better understand the etiology of cancer in these populations, the Branch is preparing to launch the Transplant Cancer Match Study, which will be a major resource for IIB. This will be a collaborative effort with the Health Resources and Services Administration, which oversees the U.S. solid organ transplant network. Data from multiple state and regional cancer registries will be linked with the U.S. registry of transplant recipients (360,000 individuals), candidates, and donors, as well as with a registry of 1.7 million end-stage renal disease patients. Strengths of the study include its large size, the availability of detailed data on potential risk factors in transplant recipients, (e.g., underlying conditions, viral infections, and medications), and population-based cancer ascertainment. Matching is anticipated for FY2007-2009, with analyses to continue into FY2010.
Immunity and Chimerism
IIB plans to use newly developed, ultra-sensitive technology to detect maternal DNA in neonatal or infant circulation. Analyses will clarify whether mother-to-infant transmission of HIV results from leakage of maternal blood across the placenta and then tolerance of allogeneic cells in the infant. If the results of this pilot study support the hypothesis that chimerism accounts for HIV transmission, during FY2008 this technology would be used to test other hypotheses using previously collected specimens. One, using Jamaican specimens, would examine the possibility that chimerism accounts for breast feeding transmission of HTLV-I. A second, using specimens from South Africa, would examine post-transplant KS tissue for evidence of donor DNA. A third would look for donor DNA in malignancies occurring in Danish transplant recipients identified through linkage of registry data.
Hemophilia, HCV and HIV
Field work on the Second Multicenter Hemophilia Cohort Study (MHCS-II) was completed in FY2005. From 2001 – 2005, incidence rates of lymphoma and hepatocellular carcinoma were lower than anticipated. This ended 23 years of research primarily on HIV/AIDS and HCV. The data and large collection of blood specimens are in safekeeping and have been made available to qualified investigators via http://mhcs-ii.rti.org. As a resource particularly for fellows, analyses in FY2007-2008 will include demographic, clinical, and host genetic correlates of HCV clearance and viral load, as well as late complications of HIV. In FY2009, IIB plans to contact a sample of the 54 centers that participated in the MHCS-II to request data on major outcomes of interest, including deaths, AIDS diagnoses, cancers, liver transplants, and other manifestations of end-stage liver disease. Based on response rates and statistical power from this pilot, the same data would be requested from the remainder of the centers in FY2010. Risk of the outcomes would be compared using baseline and longitudinal (2001 – 2005) MHCS-II data and specimens.
Microbiomics and Cancer Risk
Chronic inflammation from infection is related to cancer risk, as demonstrated by H. pylori with gastric cancer and periodontal hygiene with oral and esophageal cancers. There are hundreds and perhaps thousands of currently unidentified, mostly anaerobic bacterial species in the lumen or attached to the epithelium of the colon. New technologies, based on 16s rRNA sequence relationships, can categorize and obtain the relative quantity of all species, known and unknown. IIB is organizing a DCEG working group and in FY2007 will initiate collaborations with genomists and statisticians to assess oligonucleotide-based chip and other technologies. Two or more technologies will be pursued, starting with pilot studies in FY2008 to assess sensitivity, specificity, and reproducibility with various types and conditions of specimens. When deemed satisfactory, probably in FY2008-2009, previously collected specimens from colon and oro-pharyngeal cancer case-control studies will be examined. If these results are promising, in FY2009-2010 collaborations with others holding suitable specimens and data will be established to characterize the relationships of alimentary tract, urinary, and potentially other cancers to the full spectrum of microbial flora.
