Ovarian cancer is the leading cause of death from gynecological tumors and the fourth most frequent cause of death from cancer in women. In 2005, it is estimated that 22,220 new cases will be diagnosed and 16,210 women will die of the disease in the U.S. (American Cancer Society Facts and Figures, 2005). The high lethality of invasive epithelial ovarian cancer (ovarian cancer) is primarily due to the advanced stage at which it is typically diagnosed, when curative therapy is ineffective. Efforts at early diagnosis have been frustrated by the poor performance of screening methods. Thus, there is tremendous need for increased information about the risk factors for and underlying causes of ovarian cancer. The cause of ovarian cancer is unknown, but is thought to be multifactorial, with hormonal, genetic, and environmental factors playing a role. The most strongly established hypothesis focuses on ovulation and/or reproductive hormones and is based upon consistent epidemiological evidence and corroborative in vitro experimental results. In addition, genetic factors play a role, with increased risk in relatives of ovarian cancer patients. At present, these observations offer the most promising clues to ovarian cancer biology. An attractive hypothesis is that a significant part of the genetic risk may be due to variation in genes that influence reproductive endocrinology. We are testing the association between variation in genes involved in gonadotropin signaling and risk of ovarian cancer using samples from two completed case-controls studies. We are requesting funds here to expand the sample size of this data set by genotyping additional cases and controls from a third recently completed ovarian cancer study with the aims of (1) providing robust results of the association between variation in genes involved in gonadotropin signaling and risk of ovarian cancer, (2) exploring the relationship between variation in genes involved in gonadotropin signaling and risk of ovarian cancer by histology and environmental exposures such as oral contraceptive use, parity, and menopausal hormone therapy and (3) conducing a 'gonadotropin signaling pathway analysis' to understand the complex manner in which these gene jointly influence ovarian cancer risk. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA115195-02
Application #
7214106
Study Section
Special Emphasis Panel (ZCA1-SRRB-Q (J1))
Program Officer
Schully, Sheri D
Project Start
2006-04-01
Project End
2009-03-31
Budget Start
2007-04-12
Budget End
2009-03-31
Support Year
2
Fiscal Year
2007
Total Cost
$79,137
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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
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
Liu, Gang; Mukherjee, Bhramar; Lee, Seunggeun et al. (2018) Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence. Am J Epidemiol 187:366-377
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
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
Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H et al. (2017) History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomarkers Prev 26:1470-1473
Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan et al. (2017) Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. Br J Cancer 116:524-535

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