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Grant Details

Grant Number: 5R01CA076016-12 Interpret this number
Primary Investigator: Schildkraut, Joellen
Organization: Duke University
Project Title: The Molecular Epidemiology of Ovarian Cancer
Fiscal Year: 2010
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Abstract

In the current funding period of our study entitled 'The Molecular Epidemiology of Ovarian Cancer' (RO1CA176016, PI: Dr. Schildkraut,), we have studied the relationship between candidate genes in the DNA damage and repair pathway and ovarian cancer risk using data from the North Carolina Ovarian Cancer Study (NCOCS). To date, we have examined the relationship between 53 genes and 652 SNPs in this pathway. The first phase of our study we have identified strong association between genes on the DNA repair pathway and ovarian cancer risk. In this competitive renewal we propose to expand the scope of our Phase 1 genotyping to further investigate genes the DNA repair and apopotosis pathways and to mount a second candidate gene association study. We hypothesize that a subset of the previouslyexamined SNPs in genes with known roles in DNA damage and repair will emerge as risk factors for ovarian cancer, and that newly-examined SNPs in genes within this and related pathways will be associated with risk of ovarian cancer. The proposed study will be designed to optimally accumulate evidence on candidates while simultaneously reducing the false positive rate among included SNPs and minimizing the rate of false negatives. Analyses will examine risk modification across subgroups defined by age, race, body mass index, oral contraceptive use, pregnancy history, histology and other exposures. The ultimate goal is to improve our ability to identify women at genetic risk of ovarian cancer and to design targeted intervention strategies to prevent this fatal disease. To this end, we propose to genotype in 2,075 invasive serous epithelial ovarian cancer cases and 2,075 age-matched controls of European descent to determine the relationship between genetic variants in DNA response and repair and related pathways. We will evaluate the association between over 2,000 SNPs with risk of ovarian cancer. We will access subjects from six independent case-control studies: North Carolina (Dr.Schildkraut), the Mayo Clinic (Dr. Goode), New England (Drs. Terry and Cramer), Pittsburgh (Dr. Ness), Los Angeles (Drs. Pearce and Wu) and Seattle (Dr. Rossing). Further confirmation will be pursued in collaboration with the Ovarian Cancer Association Consortium (OCAC) in the future.

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Publications

Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium.
Authors: Trabert B, Ness RB, Lo-Ciganic WH, Murphy MA, Goode EL, Poole EM, Brinton LA, Webb PM, Nagle CM, Jordan SJ, Australian Ovarian Cancer Study Group, Australian Cancer Study (Ovarian Cancer), Risch HA, Rossing MA, Doherty JA, Goodman MT, Lurie G, Kjær SK, Hogdall E, Jensen A, Cramer DW, Terry KL, Vitonis A, Bandera EV, Olson S, King MG, Chandran U, Anton-Culver H, Ziogas A, Menon U, Gayther SA, Ramus SJ, Gentry-Maharaj A, Wu AH, Pearce CL, Pike MC, Berchuck A, Schildkraut JM, Wentzensen N, Ovarian Cancer Association Consortium
Source: J Natl Cancer Inst, 2014 Feb;106(2), p. djt431.
PMID: 24503200
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Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls.
Authors: Terry KL, Karageorgi S, Shvetsov YB, Merritt MA, Lurie G, Thompson PJ, Carney ME, Weber RP, Akushevich L, Lo-Ciganic WH, Cushing-Haugen K, Sieh W, Moysich K, Doherty JA, Nagle CM, Berchuck A, Pearce CL, Pike M, Ness RB, Webb PM, Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Rossing MA, Schildkraut J, Risch H, Goodman MT, Ovarian Cancer Association Consortium
Source: Cancer Prev Res (Phila), 2013 Aug;6(8), p. 811-21.
EPub date: 2013 Jun 12.
PMID: 23761272
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Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.
Authors: Pearce CL, Rossing MA, Lee AW, Ness RB, Webb PM, for Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Chenevix-Trench G, Jordan SM, Stram DA, Chang-Claude J, Hein R, Nickels S, Lurie G, Thompson PJ, Carney ME, Goodman MT, Moysich K, Hogdall E, Jensen A, Goode EL, Fridley BL, Cunningham JM, Vierkant RA, Weber RP, Ziogas A, Anton-Culver H, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Brinton L, Wentzensen N, Lissowska J, Garcia-Closas M, Massuger LF, Kiemeney LA, Van Altena AM, Aben KK, Berchuck A, Doherty JA, Iversen E, McGuire V, Moorman PG, Pharoah P, Pike MC, Risch H, Sieh W, Stram DO, Terry KL, Whittemore A, Wu AH, Schildkraut JM, Kjaer SK, Ovarian Cancer Association Consortium
Source: Cancer Epidemiol Biomarkers Prev, 2013 May;22(5), p. 880-90.
EPub date: 2013 Mar 5.
PMID: 23462924
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Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies.
Authors: Faber MT, Kjær SK, Dehlendorff C, Chang-Claude J, Andersen KK, Høgdall E, Webb PM, Jordan SJ, Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Rossing MA, Doherty JA, Lurie G, Thompson PJ, Carney ME, Goodman MT, Ness RB, Modugno F, Edwards RP, Bunker CH, Goode EL, Fridley BL, Vierkant RA, Larson MC, Schildkraut J, Cramer DW, Terry KL, Vitonis AF, Bandera EV, Olson SH, King M, Chandran U, Kiemeney LA, Massuger LF, van Altena AM, Vermeulen SH, Brinton L, Wentzensen N, Lissowska J, Yang HP, Moysich KB, Odunsi K, Kasza K, Odunsi-Akanji O, Song H, Pharaoh P, Shah M, Whittemore AS, McGuire V, Sieh W, Sutphen R, Menon U, Gayther SA, Ramus SJ, Gentry-Maharaj A, Pearce CL, Wu AH, Pike MC, Risch HA, Jensen A, Ovarian Cancer Association Consortium
Source: Cancer Causes Control, 2013 May;24(5), p. 989-1004.
EPub date: 2013 Mar 2.
PMID: 23456270
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Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.
Authors: Olsen CM, Nagle CM, Whiteman DC, Ness R, Pearce CL, Pike MC, Rossing MA, Terry KL, Wu AH, Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Risch HA, Yu H, Doherty JA, Chang-Claude J, Hein R, Nickels S, Wang-Gohrke S, Goodman MT, Carney ME, Matsuno RK, Lurie G, Moysich K, Kjaer SK, Jensen A, Hogdall E, Goode EL, Fridley BL, Vierkant RA, Larson MC, Schildkraut J, Hoyo C, Moorman P, Weber RP, Cramer DW, Vitonis AF, Bandera EV, Olson SH, Rodriguez-Rodriguez L, King M, Brinton LA, Yang H, Garcia-Closas M, Lissowska J, Anton-Culver H, Ziogas A, Gayther SA, Ramus SJ, Menon U, Gentry-Maharaj A, Webb PM, Ovarian Cancer Association Consortium
Source: Endocr Relat Cancer, 2013 Apr;20(2), p. 251-62.
EPub date: 2013 Mar 22.
PMID: 23404857
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Inherited variants in regulatory T cell genes and outcome of ovarian cancer.
Authors: Goode EL, DeRycke M, Kalli KR, Oberg AL, Cunningham JM, Maurer MJ, Fridley BL, Armasu SM, Serie DJ, Ramar P, Goergen K, Vierkant RA, Rider DN, Sicotte H, Wang C, Winterhoff B, Phelan CM, Schildkraut JM, Weber RP, Iversen E, Berchuck A, Sutphen R, Birrer MJ, Hampras S, Preus L, Gayther SA, Ramus SJ, Wentzensen N, Yang HP, Garcia-Closas M, Song H, Tyrer J, Pharoah PP, Konecny G, Sellers TA, Ness RB, Sucheston LE, Odunsi K, Hartmann LC, Moysich KB, Knutson KL
Source: PLoS One, 2013;8(1), p. e53903.
EPub date: 2013 Jan 30.
PMID: 23382860
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Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium.
Authors: Kelemen LE, Bandera EV, Terry KL, Rossing MA, Brinton LA, Doherty JA, Ness RB, Kjaer SK, Chang-Claude J, Köbel M, Lurie G, Thompson PJ, Carney ME, Moysich K, Edwards R, Bunker C, Jensen A, Høgdall E, Cramer DW, Vitonis AF, Olson SH, King M, Chandran U, Lissowska J, Garcia-Closas M, Yang H, Webb PM, Schildkraut JM, Goodman MT, Risch HA, Australian Ovarian Cancer Study Group and Australian Cancer Study (Ovarian Cancer), Ovarian Cancer Association Consortium
Source: BMC Cancer, 2013 Jan 22;13, p. 28.
EPub date: 2013 Jan 22.
PMID: 23339562
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Global ovarian cancer health disparities.
Authors: Chornokur G, Amankwah EK, Schildkraut JM, Phelan CM
Source: Gynecol Oncol, 2013 Apr;129(1), p. 258-64.
EPub date: 2012 Dec 22.
PMID: 23266352
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Vitamin D receptor (VDR) polymorphisms and risk of ovarian cancer in Caucasian and African American women.
Authors: Grant DJ, Hoyo C, Akushevich L, Iversen ES, Whitaker R, Marks J, Berchuck A, Schildkraut JM
Source: Gynecol Oncol, 2013 Apr;129(1), p. 173-8.
EPub date: 2012 Dec 21.
PMID: 23262379
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ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer Association Consortium.
Authors: Poole EM, Gates MA, High BA, Chanock SJ, Cramer DW, Cunningham JM, Fridley BL, Gayther SA, Goode EL, Iversen ES, Lissowska J, Palmieri Weber RT, Pharoah PD, Phelan CM, Ramus SJ, Schildkraut JM, Sutphen R, Tsai YY, Tyrer J, Vierkant RA, Wentzensen N, Yang HP, Terry KL, Tworoger SS
Source: Cancer Causes Control, 2012 Nov;23(11), p. 1805-10.
EPub date: 2012 Sep 8.
PMID: 22961099
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Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies.
Authors: Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A, Ovarian Cancer Association Consortium
Source: Lancet Oncol, 2012 Apr;13(4), p. 385-94.
EPub date: 2012 Feb 22.
PMID: 22361336
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Ovarian cancer risk associated with inherited inflammation-related variants.
Authors: White KL, Schildkraut JM, Palmieri RT, Iversen ES Jr, Berchuck A, Vierkant RA, Rider DN, Charbonneau B, Cicek MS, Sutphen R, Birrer MJ, Pharoah PP, Song H, Tyrer J, Gayther SA, Ramus SJ, Wentzensen N, Yang HP, Garcia-Closas M, Phelan CM, Cunningham JM, Fridley BL, Sellers TA, Goode EL, Ovarian Cancer Association Consortium
Source: Cancer Res, 2012 Mar 1;72(5), p. 1064-9.
EPub date: 2012 Jan 26.
PMID: 22282663
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Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk.
Authors: Pearce CL, Doherty JA, Van Den Berg DJ, Moysich K, Hsu C, Cushing-Haugen KL, Conti DV, Ramus SJ, Gentry-Maharaj A, Menon U, Gayther SA, Pharoah PD, Song H, Kjaer SK, Hogdall E, Hogdall C, Whittemore AS, McGuire V, Sieh W, Gronwald J, Medrek K, Jakubowska A, Lubinski J, Chenevix-Trench G, AOCS/ACS Study Group, Beesley J, Webb PM, Berchuck A, Schildkraut JM, Iversen ES, Moorman PG, Edlund CK, Stram DO, Pike MC, Ness RB, Rossing MA, Wu AH
Source: Hum Mol Genet, 2011 Jun 1;20(11), p. 2263-72.
EPub date: 2011 Mar 21.
PMID: 21422097
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Recreational physical activity and ovarian cancer risk and survival.
Authors: Moorman PG, Jones LW, Akushevich L, Schildkraut JM
Source: Ann Epidemiol, 2011 Mar;21(3), p. 178-87.
PMID: 21296269
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Genetics and women's health issues--the commitment of EMS to women scientists and gender-associated disease topics.
Authors: Witt KL, Moorman PG, Kovalchuk O, Holland N, Block G, Andreassen PR
Source: Environ Mol Mutagen, 2010 Oct-Dec;51(8-9), p. 774-80.
PMID: 20740639
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Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.
Authors: Schildkraut JM, Iversen ES, Wilson MA, Clyde MA, Moorman PG, Palmieri RT, Whitaker R, Bentley RC, Marks JR, Berchuck A
Source: PLoS One, 2010 Apr 8;5(4), p. e10061.
EPub date: 2010 Apr 8.
PMID: 20386703
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Primary peritoneal and ovarian cancers: an epidemiological comparative analysis.
Authors: Grant DJ, Moorman PG, Akushevich L, Palmieri RT, Bentley RC, Schildkraut JM
Source: Cancer Causes Control, 2010 Jul;21(7), p. 991-8.
EPub date: 2010 Mar 23.
PMID: 20309725
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