Abstract

In this five-year project, laboratory analyses will be performed to characterize study subjects for known polymorphisms in genes regulating steroid metabolism, catecholestrogen formation, and detoxification of oxidative damage. Banked DNA samples from 441 ovarian cancer cases and 430 controls will be used to test the following hypotheses: 1) high-activity genotypes for the steroid metabolism genes CYP17 and EDH17B2 that increase concentrations of estrogen are associated with a greater risk of ovarian cancer; 2) high-activity genotypes for CYP1A1, CYP1B1, and MnSOD that increase contentrations of 4- hydroxylated catecholestrogens and oxidative stress, or low-activity genotypes for COMT and GST that decrease the detoxification of activated catecholestrogens, are positively associated with ovarian cancer risk; 3) high-activity genotypes for AhR and CYP1A2 that increase concentrations of 2-hydroxylated catecholestrogens are inversely associated with ovarian cancer risk. Dr. Anna Wu, the P.I. on the Los Angeles sub-contract during the first cycle of this grant, will assist with statistical analysis and the interpretation of results.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058598-08
Application #
6633147
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Patel, Appasaheb1 R
Project Start
1993-08-15
Project End
2006-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
8
Fiscal Year
2003
Total Cost
$478,920
Indirect Cost

  Institution

Name
University of Hawaii
Department
Type
Organized Research Units
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822

  Publications

Earp, Madalene; Tyrer, Jonathan P; Winham, Stacey J et al. (2018) Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility. PLoS One 13:e0197561
O'Mara, Tracy A; Glubb, Dylan M; Amant, Frederic et al. (2018) Identification of nine new susceptibility loci for endometrial cancer. Nat Commun 9:3166
Harris, Holly R; Babic, Ana; Webb, Penelope M et al. (2018) Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomarkers Prev 27:174-182
Lu, Yingchang; Beeghly-Fadiel, Alicia; Wu, Lang et al. (2018) A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk. Cancer Res 78:5419-5430
Peres, Lauren C; Risch, Harvey; Terry, Kathryn L et al. (2018) Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled analysis of 12 case-control studies. Int J Epidemiol 47:460-472
Ong, Jue-Sheng; Hwang, Liang-Dar; Cuellar-Partida, Gabriel et al. (2018) Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study. Int J Epidemiol 47:450-459
Praestegaard, Camilla; Jensen, Allan; Jensen, Signe M et al. (2017) Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies. Int J Cancer 140:2422-2435
Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J et al. (2017) Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci. Oncotarget 8:64670-64684
Phelan, Catherine M (see original citation for additional authors) (2017) Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet 49:680-691
Reid, Brett M; Permuth, Jennifer B; Chen, Y Ann et al. (2017) Integration of Population-Level Genotype Data with Functional Annotation Reveals Over-Representation of Long Noncoding RNAs at Ovarian Cancer Susceptibility Loci. Cancer Epidemiol Biomarkers Prev 26:116-125

Showing the most recent 10 out of 123 publications