The goal of this K07 Career Award training is to acquire expertise in the requisite disciplines for molecular and genetic cancer epidemiology research, with an emphasis on femal cancers. Two interlocking areas of study will be pursued. First, a series of independent studies, laboratory projects and seminars/conferences will provide an understanding of the laboratory techniques employed in genetic epidemiology studies, the underlying biology of female cancers, and the clinical relevance of genetic epidemiology research. Second, studies in epidemiology and biostatistics will ensure the development of study design, management and analysis skills. The cornerstone of this training will be a study investigating ovarian cancer risks and survival among BRCA1/2 mutation carriers. Because the case fatality rate of ovarian cancer is so high, many doctors advise these high-risk women to engage in the two behaviors that most strongly prevent ovarian cancer: using oral contraceptives (Ocs) and bearing more children. While one recent study did find Ocs to be protective for BRCA1/2 carriers, concerns about the study's design question its validity. Moreover, one report suggests that for BRCA1/2 mutation carriers, OC use substantially increases breast cancer risk. Another study suggests that having more children increases (rather than decreases) ovarian cancer risk in these women. There are also contradictory findings on the survival of BRCA1/2-associated ovarian cancer patients. Therefore, a well-designed study investigating the effect of OC use and parity on ovarian cancer risk and survival in BRCA1/2 carriers is urgently needed. We will use a case-only study to determine the protectiveness of Ocs and parity against ovarian cancer among women carrying BRCA1/2 mutations versus among women not carrying these mutations, and we will determine whether there is a survival difference between the two groups. We will obtain BRCA1/2 mutation status from banked tissue specimens of about 400 Ashkenazi Jewish women with ovarian cancer identified from tumor registries in Pennsylvania, Ohio, New York and Florida or who participated in an NIH-sponsored study. We will link these results to information on OC use and parity. The protection afforded by OC use and parity will then be compared among BRCA1/2 mutation carriers versus among non-carriers. Survival status will be obtained from the National Death Index and the differences in survival between the two groups will be compared. The information from this study will have immediate implications for clinical practice and for the design of clinical trials. Additionally, this training will provide the skills and experience needed to become an independent researcher in the molecular and genetic epidemiology of female cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA080668-02
Application #
6377037
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$129,202
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Block, Matthew S; Vierkant, Robert A; Rambau, Peter F et al. (2018) MyD88 and TLR4 Expression in Epithelial Ovarian Cancer. Mayo Clin Proc 93:307-320
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
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
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

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