This project is a comprehensive, multidisciplinary effort to understand the natural history and modes of transmission of viruses and other infectious agents that are associated with cancer. With numerous intramural and extramural laboratory, clinical, and epidemiologic collaborators, and a core of prospective cohort and case-control studies, the effort is focused on human immunodeficiency virus (HIV), human T-lymphotropic virus types I and II (HTLV-I/-II), hepatitis C virus (HCV), and Kaposi sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8 or HHV-8). The Second Multicenter Hemophilia Cohort Study (MHCS-II) has enrolled and begun prospective follow-up of more than 2000 HCV-exposed persons with hemophilia. Testing of the cohort has been initiated with newly developed Taq-Man PCR assays for detection and quantification of HCV and HIV RNA have been developed and with a newly developed sequence-based method to determine HCV genotype. Initial analyses suggest that spontaneous clearance of HCV is associated with infection relatively recent calendary years. Analyses of data from the preceding first MHCS show that non-Hodgkin lymphoma risk is very strongly related to HIV infection and older age but not to HCV or hepatitis B virus (HBV) infection. In contrast, hepatocellular carcinoma risk is strongly related to HCV infection and older age, HIV infection, or HBV infection. Use of alcohol, acetaminophen, and non-steroidal anti-inflammatory drugs, all of which may be hepatotoxic, is generally low. In a collaboration, AIDS progression rate was related to differences in genes (HLA class I and KIR) affecting innate immunity. With KSHV infection without HIV co-infection, risk for classical (non-AIDS) Kaposi sarcoma was increased with detection of KSHV in peripheral blood and with certain variants in host genes related to anti-inflammatory cytokines and immunoglobulin binding. Laboratory and field studies to clarify these associations are in progress.Among carriers of HTLV-I infection, those in Japan were found to have lower levels of HTLV-I antibodies but higher HTLV-I proviral load in peripheral blood cells than those in Jamaica. This pattern mirrors the contrasting risk of the two major outcomes of HTLV-I infection (adult T-cell leukemia/lymphoma and tropical spastic paraparesis) in these two populations.In a large cohort of injection drug users, HCV viral load was significantly higher with HIV-1 and/or HTLV-II co-infection, as well as for white men and those with longer HCV infection. In the same cohort, mortality due to liver disease was directly related to HCV viral load, which appeared to account for previously reported associations of hepatic mortality with male gender and HIV-1 co-infection.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP010176-04
Application #
7066240
Study Section
(VEB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429
Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504
Altekruse, Sean F; Shiels, Meredith S; Modur, Sharada P et al. (2018) Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS 32:513-521
AIDS-defining Cancer Project Working Group of IeDEA, COHERE in EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. AIDS 32:2777-2786
Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72
Anderegg, Nanina; Johnson, Leigh F; Zaniewski, Elizabeth et al. (2017) All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up. AIDS 31 Suppl 1:S31-S40
Drozd, Daniel R; Kitahata, Mari M; Althoff, Keri N et al. (2017) Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North America Compared With the General Population. J Acquir Immune Defic Syndr 75:568-576
Dubrow, Robert; Qin, Li; Lin, Haiqun et al. (2017) Association of CD4+ T-cell Count, HIV-1 RNA Viral Load, and Antiretroviral Therapy With Kaposi Sarcoma Risk Among HIV-infected Persons in the United States and Canada. J Acquir Immune Defic Syndr 75:382-390
Jiamsakul, Awachana; Kariminia, Azar; Althoff, Keri N et al. (2017) HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy-Results From the IeDEA Collaboration. J Acquir Immune Defic Syndr 76:319-329
Muzaale, A D; Althoff, K N; Sperati, C J et al. (2017) Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors. Am J Transplant 17:1823-1832

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