In the United States in 1997, it has been estimated that there were more than 26,000 new cases of cancer of the ovary, and that approximately 14,000 women died from it, making it the most lethal of the gynecological malignancies. Close to 2 percent of women are affected during their lifetimes. Ovarian cancer is difficult to treat because patients frequently present late in the disease course, which may be asymptomatic until advanced stages. The few established risk factors do not appear to account for a large fraction of disease incidence, and the possible mechanisms by which these factors affect risk of developing ovarian cancer are still not well understood. Based upon a substantial body of pathologic, endocrinology and epidemiologic evidence, we have recently suggested a new hormonal hypothesis regarding the etiology of ovarian cancer. To examine this hypothesis, we are conducting, in the state of Connecticut, a population-based case-control interview study which will examine a collection of factors related to hormonal expression during and after the reproductive years. In total, about 580 ovarian-cancer cases aged 35-79 years are being identified prospectively in the state through our Rapid Case Ascertainment system, and 1,000 randomly selected population controls are being frequency matched to the cases in three age groups. We now propose to analyze buccal-smear cell samples collected from all of the study subjects, in order to examine whether certain known, common, germline genetic polymorphism variants in the hormones and hormonal mechanisms under study are associated with altered risk of ovarian cancer. PCR methods will be used for the genetic analyses. In general, the hormonal factors being examined have received only a little attention with respect to ovarian cancer, and our ongoing project is the first to evaluate them systematically in a rigorous, large-scale study which will integrate all of the factors within a coherent etiologic framework. The new study proposed here will substantiate, through genetic considerations, the risk associations seen for the hormonal climate manifestations considered in our existing study, and may provide further insight into possible etiologic mechanisms of ovarian cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA080742-03
Application #
6350353
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Verma, Mukesh
Project Start
1999-04-01
Project End
2003-01-31
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
3
Fiscal Year
2001
Total Cost
$127,445
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
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
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
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
Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna et al. (2017) Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies. Am J Epidemiol 185:8-20
Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas et al. (2017) Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium. Br J Cancer 116:1223-1228
Cannioto, Rikki; LaMonte, Michael J; Risch, Harvey A et al. (2016) Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomarkers Prev 25:1114-24

Showing the most recent 10 out of 37 publications