We propose to continue multi-disciplinary studies of the role of human papillomaviruses (HPV) in the etiology of anogenital cancers. The program incorporates epidemiologic and molecular biology approaches in the three projects, with support form four core functions including virology, pathology, biostatistics and administrative support. The nucleus of this effort is a series of case-control studies investigating the risk factor involved in squamous cell cervical cancer, anal cancer, vulvar cancer, vaginal cancer, adenocarcinoma of the cervix and penile cancers. The results from these studiers will increase the data base developed over the past thirteen years of this Program Project. Established polymerase chain reaction procedures for identification of HPV DNA together with the serologic tests developed in this program will continue to be used to establish virus infection and evidence of immune responses. A new focus on the occurrence of multiple cancers of the genital area is introduced, with the goal of establishing the primary and/or secondary state of tumors subsequent to an initial diagnosis. A group of women who have developed at least one additional primary anogenital cancer will be re- interviewed, together with appropriate controls, about exposures that may have contributed to the risk of a second primary tumor. Tissue and blood samples will be acquired for virus sequence, serologic and genetic testing. Determinations will be made of the uniqueness of the viral integration sites and the contribution of virus variants to the disease process. Studies of the roles of HLA genotypes in susceptibility to HPV- initiated cancer will be expanded. Comparative genome hybridization will continue to be used to id4entify loss or gain of chromosome regions and microarray methods used to investigate abnormal genes expression, with a particular focus of genes mapping on chromosomes 3, 5, and 20.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA042792-18
Application #
6881311
Study Section
Subcommittee G - Education (NCI)
Program Officer
Starks, Vaurice
Project Start
1987-04-10
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
18
Fiscal Year
2005
Total Cost
$1,865,736
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Leo, Paul J; Madeleine, Margaret M; Wang, Sophia et al. (2017) Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. PLoS Genet 13:e1006866
Wallace, Nicholas A; Khanal, Sujita; Robinson, Kristin L et al. (2017) High-Risk Alphapapillomavirus Oncogenes Impair the Homologous Recombination Pathway. J Virol 91:
Madeleine, Margaret M; Johnson, Lisa G; Doody, David R et al. (2016) Natural Antibodies to Human Papillomavirus 16 and Recurrence of Vulvar High-Grade Intraepithelial Neoplasia (VIN3). J Low Genit Tract Dis 20:257-60
Hardikar, Sheetal; Johnson, Lisa G; Malkki, Mari et al. (2015) A population-based case-control study of genetic variation in cytokine genes associated with risk of cervical and vulvar cancers. Gynecol Oncol 139:90-6
Wallace, Nicholas A; Robinson, Kristin; Howie, Heather L et al. (2015) ?-HPV 5 and 8 E6 disrupt homology dependent double strand break repair by attenuating BRCA1 and BRCA2 expression and foci formation. PLoS Pathog 11:e1004687
Galloway, Denise A; Laimins, Laimonis A (2015) Human papillomaviruses: shared and distinct pathways for pathogenesis. Curr Opin Virol 14:87-92
Safaeian, Mahboobeh; Johnson, Lisa G; Yu, Kai et al. (2014) Human Leukocyte Antigen Class I and II Alleles and Cervical Adenocarcinoma. Front Oncol 4:119
Madeleine, Margaret M; Carter, Joseph J; Johnson, Lisa G et al. (2014) Risk of squamous cell skin cancer after organ transplant associated with antibodies to cutaneous papillomaviruses, polyomaviruses, and TMC6/8 (EVER1/2) variants. Cancer Med 3:1440-7
Wallace, Nicholas A; Galloway, Denise A (2014) Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses. Semin Cancer Biol 26:30-42

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