Grant Details
Grant Number: |
5R01CA086888-04 Interpret this number |
Primary Investigator: |
Sellers, Thomas |
Organization: |
H. Lee Moffitt Cancer Ctr & Res Inst |
Project Title: |
Estrogen Bioactivation and Risk of Ovarian Cancer |
Fiscal Year: |
2005 |
Abstract
DESCRIPTION (provided by applicant): Among the cancers unique to women, ovarian
cancer has the highest mortality rate. Despite the public health importance of
the disease, the epidemiology is poorly understood. We propose to
systematically test the hypothesis that common genetic polymorphisms for
enzymes that catalyze pathways of estrogen and catechol estrogen formation
represent risk factors for epithelial ovarian cancer. This hypothesis will be
tested in a large case-control study conducted at the Mayo Clinic Rochester,
Mayo Clinic Jacksonville, and Duke University in North Carolina. We anticipate
recruitment of a total of 1372 incident cases (1217 Caucasian and 155 African
American). Clinic based controls matched on age, race, and state of residence
will be identified through General Internal Medicine Clinics at Mayo and
through Random Digit Dialing in North Carolina. Ovarian cancer risk factors
will be obtained through a structured interview with all cases and controls.
Blood samples orbuccal cells will be obtained as a source of DNA to detect
known, functionally significant polymorphisms in genes for cytochrome P450 1A1
(CYP1A1), cytochrome P450 1B1 (CYP1B1), catechol 0-methyltransferase (COMT),
sulfotransferase 1A1 (SULT1A1), glutathione S-transferase (GST) Ml, GST P1, and
GST Ti as well as NAD(P)H:quinone oxidoreductase (NQO1). The analytic approach
entails comparison of frequencies of alleles and genotypes for each of the
genetically polymorphic enzymes studied with: a) expected population allele and
genotype frequencies estimated from age- and race-matched control women using
conditional logistic regression. In addition, we propose to evaluate the extent
that measured non-genetic factors (e.g., reproductive history and oral
contraceptive use) might modify or confound any observed association between
these candidate genes and ovarian cancer risk. There is evidence from the
breast cancer literature that these genetic polymorphisms are important risk
factors. It is innovative, plausible, and important to evaluate similar
associations with epithelial ovarian cancer. The results could have profound
implications for our understanding of the disease.
Publications
Survival prediction based on inherited gene variation analysis.
Authors: Cicek M.S.
, Maurer M.J.
, Goode E.L.
.
Source: Methods in molecular biology (Clifton, N.J.), 2013; 1049, p. 53-64.
PMID: 23913208
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Inherited variants in regulatory T cell genes and outcome of ovarian cancer.
Authors: Goode E.L.
, DeRycke M.
, Kalli K.R.
, Oberg A.L.
, Cunningham J.M.
, Maurer M.J.
, Fridley B.L.
, Armasu S.M.
, Serie D.J.
, Ramar P.
, et al.
.
Source: PloS one, 2013; 8(1), p. e53903.
EPub date: 2013-01-30.
PMID: 23382860
Related Citations
Ovarian cancer risk associated with inherited inflammation-related variants.
Authors: White K.L.
, Schildkraut J.M.
, Palmieri R.T.
, Iversen E.S.
, Berchuck A.
, Vierkant R.A.
, Rider D.N.
, Charbonneau B.
, Cicek M.S.
, Sutphen R.
, et al.
.
Source: Cancer research, 2012-03-01; 72(5), p. 1064-9.
EPub date: 2012-01-26.
PMID: 22282663
Related Citations
Common variation in Nemo-like kinase is associated with risk of ovarian cancer.
Authors: Stevens K.N.
, Kelemen L.E.
, Wang X.
, Fridley B.L.
, Vierkant R.A.
, Fredericksen Z.
, Armasu S.M.
, Tsai Y.Y.
, Berchuck A.
, Narod S.A.
, et al.
.
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012 Mar; 21(3), p. 523-8.
EPub date: 2012-01-17.
PMID: 22253297
Related Citations
Assessment of hepatocyte growth factor in ovarian cancer mortality.
Authors: Goode E.L.
, Chenevix-Trench G.
, Hartmann L.C.
, Fridley B.L.
, Kalli K.R.
, Vierkant R.A.
, Larson M.C.
, White K.L.
, Keeney G.L.
, Oberg T.N.
, et al.
.
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Aug; 20(8), p. 1638-48.
EPub date: 2011-07-01.
PMID: 21724856
Related Citations
Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic white women: the Ovarian Cancer Association Consortium.
Authors: Phelan C.M.
, Tsai Y.Y.
, Goode E.L.
, Vierkant R.A.
, Fridley B.L.
, Beesley J.
, Chen X.Q.
, Webb P.M.
, Chanock S.
, Cramer D.W.
, et al.
.
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Feb; 19(2), p. 600-4.
PMID: 20142253
Related Citations
Inherited determinants of ovarian cancer survival.
Authors: Goode E.L.
, Maurer M.J.
, Sellers T.A.
, Phelan C.M.
, Kalli K.R.
, Fridley B.L.
, Vierkant R.A.
, Armasu S.M.
, White K.L.
, Keeney G.L.
, et al.
.
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2010-02-01; 16(3), p. 995-1007.
EPub date: 2010-01-26.
PMID: 20103664
Related Citations
Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.
Authors: Pearce C.L.
, Near A.M.
, Van Den Berg D.J.
, Ramus S.J.
, Gentry-Maharaj A.
, Menon U.
, Gayther S.A.
, Anderson A.R.
, Edlund C.K.
, Wu A.H.
, et al.
.
Source: British journal of cancer, 2009-01-27; 100(2), p. 412-20.
EPub date: 2009-01-06.
PMID: 19127255
Related Citations
Performance of amplified DNA in an Illumina GoldenGate BeadArray assay.
Authors: Cunningham J.M.
, Sellers T.A.
, Schildkraut J.M.
, Fredericksen Z.S.
, Vierkant R.A.
, Kelemen L.E.
, Gadre M.
, Phelan C.M.
, Huang Y.
, Meyer J.G.
, 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. 1781-9.
PMID: 18628432
Related Citations
Genetic variation in the one-carbon transfer pathway and ovarian cancer risk.
Authors: Kelemen L.E.
, Sellers T.A.
, Schildkraut J.M.
, Cunningham J.M.
, Vierkant R.A.
, Pankratz V.S.
, Fredericksen Z.S.
, Gadre M.K.
, Rider D.N.
, Liebow M.
, et al.
.
Source: Cancer research, 2008-04-01; 68(7), p. 2498-506.
PMID: 18381459
Related Citations
Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer.
Authors: Chien J.R.
, Aletti G.
, Bell D.A.
, Keeney G.L.
, Shridhar V.
, Hartmann L.C.
.
Source: Journal of cellular biochemistry, 2007-12-01; 102(5), p. 1117-29.
PMID: 17879946
Related Citations
Current management strategies for ovarian cancer.
Authors: Aletti G.D.
, Gallenberg M.M.
, Cliby W.A.
, Jatoi A.
, Hartmann L.C.
.
Source: Mayo Clinic proceedings, 2007 Jun; 82(6), p. 751-70.
PMID: 17550756
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