Skip to main content
Grant Details

Grant Number: 5R01CA112512-05 Interpret this number
Primary Investigator: Schwartz, Stephen
Organization: Fred Hutchinson Cancer Research Center
Project Title: Immunogenetics of Cervical and Vulvar Cancer
Fiscal Year: 2009
Back to top


Abstract

DESCRIPTION (provided by applicant): Human papilloma virus (HPV) infection is the necessary cause of all cervical neoplasia and the majority of vulvar cancer. Large population-based studies show strong familial associations among anogenital cancers. However, the specific genetic factors that contribute to HPV anogenital carcinogenesis have not been comprehensively studied. Cell-mediated immune mechanisms, including HLA and type 1 and type 2 cytokines, are crucial determinants of the host response to HPV infection. In our Program Project Grant (CA 42792), we are currently funded to examine the association between HLA class I alleles and squamous cell cervical cancer risk. This application seeks funding to expand our investigation of the immunogenetics of HPV-related anogenital cancers. Specifically, using existing DNA specimens on 460 cervical adenocarcinomas, 426 squamous cell vulvar carcinomas, and 917 population controls, we will determine associations between HLA class I and class II alleles and risks of cervical adenocarcinoma and vulvar carcinoma. We will use microsatellite markers to determine extended haplotypes of HLA alleles associated with these cancers, and with squamous cell cervical cancer (n=453), to identify additional HLA-region loci potentially involved in HPV anogenital carcinogenesis. We also will determine associations between these anogenital cancers and multiple single nucleotide polymorphisms and haplotypes in 17 cytokine genes (primarily interleukins), and their receptors or receptor antagonists (40 genes in total), known or suspected of being involved in type 1 and 2 responses or anogenital carcinogenesis. Finally, we will test the hypothesis that squamous cell cervical cancer, cervical adenocarcinoma, and squamous vulvar carcinoma are associated with common genetic variation in the chemokine receptor gene CXCR4 (mutations in which are linked to inherited impaired immune response to HPV) and its ligand, SDF1. Secondary aims include exploration of gene-gene interactions (e.g., among ligand-receptor gene pairs and genes involved in common adaptive immune response pathways) and gene-environment interactions (cigarette smoking and cytokine or cytokine receptor genotypes). This study will be the most comprehensive assessment of anogenital cancer immunogenetics to date, and will provide new information on inherited predisposition to these cancers, with potential implications for the development and/or implementation of HPV vaccines.

Back to top


Publications

HLA and KIR Associations of Cervical Neoplasia.
Authors: Bao X. , Hanson A.L. , Madeleine M.M. , Wang S.S. , Schwartz S.M. , Newell F. , Pettersson-Kymmer U. , Hemminki K. , Tiews S. , Steinberg W. , et al. .
Source: The Journal of infectious diseases, 2018-11-05; 218(12), p. 2006-2015.
PMID: 30099516
Related Citations

A population-based case-control study of genetic variation in cytokine genes associated with risk of cervical and vulvar cancers.
Authors: Hardikar S. , Johnson L.G. , Malkki M. , Petersdorf E.W. , Galloway D.A. , Schwartz S.M. , Madeleine M.M. .
Source: Gynecologic oncology, 2015 Oct; 139(1), p. 90-6.
EPub date: 2015-08-01.
PMID: 26241630
Related Citations

Genetic variation in the TLR and NF-κB pathways and cervical and vulvar cancer risk: a population-based case-control study.
Authors: Bodelon C. , Madeleine M.M. , Johnson L.G. , Du Q. , Galloway D.A. , Malkki M. , Petersdorf E.W. , Schwartz S.M. .
Source: International journal of cancer, 2014-01-15; 134(2), p. 437-44.
EPub date: 2013-08-05.
PMID: 23824834
Related Citations

Human Leukocyte Antigen Class I and II Alleles and Cervical Adenocarcinoma.
Authors: Safaeian M. , Johnson L.G. , Yu K. , Wang S.S. , Gravitt P.E. , Hansen J.A. , Carrington M. , Schwartz S.M. , Gao X. , Hildesheim A. , et al. .
Source: Frontiers in oncology, 2014; 4, p. 119.
EPub date: 2014-06-19.
PMID: 24995157
Related Citations

Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study.
Authors: Hussain S.K. , Madeleine M.M. , Johnson L.G. , Du Q. , Galloway D.A. , Daling J.R. , Malkki M. , Petersdorf E.W. , Schwartz S.M. .
Source: International journal of cancer, 2013 Jul; 133(1), p. 201-13.
EPub date: 2013-02-12.
PMID: 23280621
Related Citations

Genetic variation in CD83 and risks of cervical and vulvar cancers: a population-based case-control study.
Authors: Bodelon C. , Madeleine M.M. , Johnson L.G. , Du Q. , Malkki M. , Petersdorf E.W. , Schwartz S.M. .
Source: Gynecologic oncology, 2012 Mar; 124(3), p. 525-8.
EPub date: 2011-11-28.
PMID: 22134374
Related Citations

Parity and HLA alleles in risk of rheumatoid arthritis.
Authors: Guthrie K.A. , Gammill H.S. , Madeleine M.M. , Dugowson C.E. , Nelson J.L. .
Source: Chimerism, 2011 Jan; 2(1), p. 11-5.
PMID: 21547030
Related Citations

Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.
Authors: Johnson L.G. , Schwartz S.M. , Malkki M. , Du Q. , Petersdorf E.W. , Galloway D.A. , Madeleine M.M. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Jan; 20(1), p. 199-207.
EPub date: 2010-11-11.
PMID: 21071541
Related Citations

Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study.
Authors: Maley S.N. , Schwartz S.M. , Johnson L.G. , Malkki M. , Du Q. , Daling J.R. , Li S.S. , Zhao L.P. , Petersdorf E.W. , Madeleine M.M. .
Source: International journal of immunogenetics, 2009 Dec; 36(6), p. 367-75.
EPub date: 2009-09-24.
PMID: 19788587
Related Citations

A systematic search for SNPs/haplotypes associated with disease phenotypes using a haplotype-based stepwise procedure.
Authors: Yang Y. , Li S.S. , Chien J.W. , Andriesen J. , Zhao L.P. .
Source: BMC genetics, 2008-12-22; 9, p. 90.
EPub date: 2008-12-22.
PMID: 19102730
Related Citations

Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.
Authors: Hussain S.K. , Madeleine M.M. , Johnson L.G. , Du Q. , Malkki M. , Wilkerson H.W. , Farin F.M. , Carter J.J. , Galloway D.A. , Daling J.R. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Jul; 17(7), p. 1790-9.
PMID: 18628433
Related Citations

Comprehensive analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and squamous cell cervical cancer risk.
Authors: Madeleine M.M. , Johnson L.G. , Smith A.G. , Hansen J.A. , Nisperos B.B. , Li S. , Zhao L.P. , Daling J.R. , Schwartz S.M. , Galloway D.A. .
Source: Cancer research, 2008-05-01; 68(9), p. 3532-9.
PMID: 18451182
Related Citations

Evaluation of the association with cervical cancer of polymorphisms in syndecan-1, a heparan sulfate proteoglycan involved with viral cell entry.
Authors: Yu K.J. , Bashirova A. , Madeleine M.M. , Cheng J. , Johnson L.G. , Schwartz S.M. , Carrington M. , Hildesheim A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Nov; 16(11), p. 2504-8.
PMID: 18006945
Related Citations

A haplotype-linkage analysis method for estimating recombination rates using dense SNP trio data.
Authors: Zhao L.P. , Li S.S. , Shen F. .
Source: Genetic epidemiology, 2007 Feb; 31(2), p. 154-72.
PMID: 17219374
Related Citations

Empirical vs Bayesian approach for estimating haplotypes from genotypes of unrelated individuals.
Authors: Li S.S. , Cheng J.J. , Zhao L.P. .
Source: BMC genetics, 2007-01-29; 8, p. 2.
EPub date: 2007-01-29.
PMID: 17261196
Related Citations




Back to Top