Skip Navigation
Grant Details

Grant Number: 5R01CA058598-14 Interpret this number
Primary Investigator: Goodman, Marc
Organization: University Of Hawaii At Manoa
Project Title: Collaborative Genetic Study of Ovarian Cancer Risk
Fiscal Year: 2012
Back to top


Abstract

DESCRIPTION (provided by applicant): This is a resubmission of a competitive renewal application of the Collaborative Study of Ovarian Cancer (R01- CA58598), a population-based case-control study in its second funding cycle. In this application, we follow-up on several leads from our data to examine a novel role for the vitamin D endocrine / signaling pathway in the etiology of ovarian cancer associated with proteolytic degradation of the ovulatory follicle, as well as post- ovulatory tissue remodeling that accompany healing and repair of the traumatized ovarian tissue. In addition to the genes involved with vitamin D metabolism, we have included key signaling pathways targeted by vitamin D and its receptor complex that influence the dynamic equilibrium between the extracellular matrix and ovarian epithelial cells during the wounding and repair associated with ovulation. The ovarian surface epithelium is subject to repeated wounding and healing during ovulation. It is thought that this repeated proliferative stimulation may be a key pathway to the malignant transformation of ovarian epithelial cells. The study methodology is based on a three-stage design within the Ovarian Cancer Association Consortium in which we will examine genetic variation in the vitamin D endocrine / signaling pathway that might influence the risk of ovarian cancer. Aim 1 will include a two-stage analysis of 2,930 cases and frequency-matched controls, identified in Hawaii and six other geographic areas, to identify common variants among ~3000 tagSNPs in genes that may be related to the malignant transformation of the ovary. In Aim 2 (Stage 3), we will conduct a validation study of a reduced set of ~62 (~2%) of the most promising SNPs from Aim 1 among 5,236 OvCa cases and frequency-matched controls in an independent set of six case-control studies. As part of our analysis, we will examine gene-environment and gene-gene interactions. This study fulfills key missions of the NCI's Epidemiology and Genetics Research Program by potentially providing new insights into the biology of ovarian malignancy and into the complex interactions of host genetics with environment and lifestyle in the carcinogenic process. The identification of ovarian cancer susceptibility genes that are related to ovarian surface epithelium tissue remodeling might shed light on novel vitamin D-associated enzymatic pathways in this malignancy. PUBLIC HEALTH RELEVANCE: Although ovarian cancer only accounts for 3% of new malignancies among women in the U.S., it is the fifth most common cause of cancer mortality and is the cause of 6% of all cancer deaths. There is an urgent need to establish a panel of genetic variants associated with ovarian cancer susceptibility that can be used in combination with known epidemiological risk factors to identify higher-risk women. The identification of ovarian cancer susceptibility genes that are related to OSE wounding and post-ovulatory tissue remodeling might shed light on important vitamin D-associated pathways in the carcinogenic process.

Back to top


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
Related Citations

Back to top


ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: a comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas.
Authors: Johnatty SE, Beesley J, Gao B, Chen X, Lu Y, Law MH, Henderson MJ, Russell AJ, Hedditch EL, Emmanuel C, Fereday S, Webb PM, Australian Ovarian Cancer Study Group, Goode EL, Vierkant RA, Fridley BL, Cunningham JM, Fasching PA, Beckmann MW, Ekici AB, Hogdall E, Kjaer SK, Jensen A, Hogdall C, Brown R, Paul J, Lambrechts S, Despierre E, Vergote I, Lester J, Karlan BY, Heitz F, du Bois A, Harter P, Schwaab I, Bean Y, Pejovic T, Levine DA, Goodman MT, Camey ME, Thompson PJ, Lurie G, Shildkraut J, Berchuck A, Terry KL, Cramer DW, Norris MD, Haber M, MacGregor S, deFazio A, Chenevix-Trench G
Source: Gynecol Oncol, 2013 Oct;131(1), p. 8-14.
EPub date: 2013 Aug 1.
PMID: 23917080
Related Citations

Back to top


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
Related Citations

Back to top


Type I and II endometrial cancers: have they different risk factors?
Authors: Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, van den Brandt PA, van de Vijver K, Thompson PJ, Australian National Endometrial Cancer Study Group, Strom BL, Spurdle AB, Soslow RA, Shu XO, Schairer C, Sacerdote C, Rohan TE, Robien K, Risch HA, Ricceri F, Rebbeck TR, Rastogi R, Prescott J, Polidoro S, Park Y, Olson SH, Moysich KB, Miller AB, McCullough ML, Matsuno RK, Magliocco AM, Lurie G, Lu L, Lissowska J, Liang X, Lacey JV Jr, Kolonel LN, Henderson BE, Hankinson SE, Håkansson N, Goodman MT, Gaudet MM, Garcia-Closas M, Friedenreich CM, Freudenheim JL, Doherty J, De Vivo I, Courneya KS, Cook LS, Chen C, Cerhan JR, Cai H, Brinton LA, Bernstein L, Anderson KE, Anton-Culver H, Schouten LJ, Horn-Ross PL
Source: J Clin Oncol, 2013 Jul 10;31(20), p. 2607-18.
EPub date: 2013 Jun 3.
PMID: 23733771
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium.
Authors: Setiawan VW, Pike MC, Karageorgi S, Deming SL, Anderson K, Bernstein L, Brinton LA, Cai H, Cerhan JR, Cozen W, Chen C, Doherty J, Freudenheim JL, Goodman MT, Hankinson SE, Lacey JV Jr, Liang X, Lissowska J, Lu L, Lurie G, Mack T, Matsuno RK, McCann S, Moysich KB, Olson SH, Rastogi R, Rebbeck TR, Risch H, Robien K, Schairer C, Shu XO, Spurdle AB, Strom BL, Thompson PJ, Ursin G, Webb PM, Weiss NS, Wentzensen N, Xiang YB, Yang HP, Yu H, Horn-Ross PL, De Vivo I, Australian National Endometrial Cancer Study Group
Source: Am J Epidemiol, 2012 Aug 15;176(4), p. 269-78.
EPub date: 2012 Jul 23.
PMID: 22831825
Related Citations

Back to top


Genome-wide association study for ovarian cancer susceptibility using pooled DNA.
Authors: Lu Y, Chen X, Beesley J, Johnatty SE, Defazio A, Australian Ovarian Cancer Study (AOCS) Study Group, Lambrechts S, Lambrechts D, Despierre E, Vergotes I, Chang-Claude J, Hein R, Nickels S, Wang-Gohrke S, Dörk T, Dürst M, Antonenkova N, Bogdanova N, Goodman MT, Lurie G, Wilkens LR, Carney ME, Butzow R, Nevanlinna H, Heikkinen T, Leminen A, Kiemeney LA, Massuger LF, van Altena AM, Aben KK, Kjaer SK, Høgdall E, Jensen A, Brooks-Wilson A, Le N, Cook L, Earp M, Kelemen L, Easton D, Pharoah P, Song H, Tyrer J, Ramus S, Menon U, Gentry-Maharaj A, Gayther SA, Bandera EV, Olson SH, Orlow I, Rodriguez-Rodriguez L, Macgregor S, Chenevix-Trench G
Source: Twin Res Hum Genet, 2012 Oct;15(5), p. 615-23.
EPub date: 2012 Jul 13.
PMID: 22794196
Related Citations

Back to top


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
Related Citations

Back to top


Cataract and ovarian carcinoma: is the vitamin D hypothesis alive?
Authors: Lurie G, Matsuno RK, Wilkens LR, Thompson PJ, Ollberding NJ, Carney ME, Goodman MT
Source: Cancer Epidemiol Biomarkers Prev, 2011 Dec;20(12), p. 2507-11.
EPub date: 2011 Oct 5.
PMID: 21976293
Related Citations

Back to top


Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.
Authors: Beesley J, Pickett HA, Johnatty SE, Dunning AM, Chen X, Li J, Michailidou K, Lu Y, Rider DN, Palmieri RT, Stutz MD, Lambrechts D, Despierre E, Lambrechts S, Vergote I, Chang-Claude J, Nickels S, Vrieling A, Flesch-Janys D, Wang-Gohrke S, Eilber U, Bogdanova N, Antonenkova N, Runnebaum IB, Dörk T, Goodman MT, Lurie G, Wilkens LR, Matsuno RK, Kiemeney LA, Aben KK, Marees T, Massuger LF, Fridley BL, Vierkant RA, Bandera EV, Olson SH, Orlow I, Rodriguez-Rodriguez L, Cook LS, Le ND, Brooks-Wilson A, Kelemen LE, Campbell I, Gayther SA, Ramus SJ, Gentry-Maharaj A, Menon U, Ahmed S, Baynes C, Pharoah PD, kConFab Investigators, Australian Ovarian Cancer Study Group, ABCTB Investigators, Muir K, Lophatananon A, Chaiwerawattana A, Wiangnon S, Macgregor S, Easton DF, Reddel RR, Goode EL, Chenevix-Trench G, Ovarian Cancer Association Consortium
Source: PLoS One, 2011;6(9), p. e24987.
EPub date: 2011 Sep 15.
PMID: 21949822
Related Citations

Back to top


Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk: pooled analysis within the Ovarian Cancer Association Consortium.
Authors: Lurie G, Wilkens LR, Thompson PJ, Shvetsov YB, Matsuno RK, Carney ME, Palmieri RT, Wu AH, Pike MC, Pearce CL, Menon U, Gentry-Maharaj A, Gayther SA, Ramus SJ, Whittemore AS, McGuire V, Sieh W, Pharoah PD, Song H, Gronwald J, Jakubowska A, Cybulski C, Lubinski J, Schildkraut JM, Berchuck A, Krüger Kjær S, Høgdall E, Fasching PA, Beckmann MW, Ekici AB, Hein A, Chenevix-Trench G, Webb PM, Beesley J, Australian Ovarian Cancer Study Group, Australian Cancer Study Group, Goodman MT, Ovarian Cancer Association Consortium
Source: PLoS One, 2011;6(6), p. e20703.
EPub date: 2011 Jun 6.
PMID: 21673961
Related Citations

Back to top


Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic white women: the Ovarian Cancer Association Consortium.
Authors: Phelan CM, Tsai YY, Goode EL, Vierkant RA, Fridley BL, Beesley J, Chen XQ, Webb PM, Chanock S, Cramer DW, Moysich K, Edwards RP, Chang-Claude J, Garcia-Closas M, Yang H, Wang-Gohrke S, Hein R, Green AC, Lissowska J, Carney ME, Lurie G, Wilkens LR, Ness RB, Pearce CL, Wu AH, Van Den Berg DJ, Stram DO, Terry KL, Whiteman DC, Whittemore AS, DiCioccio RA, McGuire V, Doherty JA, Rossing MA, Anton-Culver H, Ziogas A, Hogdall C, Hogdall E, Krüger Kjaer S, Blaakaer J, Quaye L, Ramus SJ, Jacobs I, Song H, Pharoah PD, Iversen ES, Marks JR, Pike MC, Gayther SA, Cunningham JM, Goodman MT, Schildkraut JM, Chenevix-Trench G, Berchuck A, Sellers TA, Ovarian Cancer Association Consortium, Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group
Source: Cancer Epidemiol Biomarkers Prev, 2010 Feb;19(2), p. 600-4.
PMID: 20142253
Related Citations

Back to top


Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer.
Authors: Schildkraut JM, Goode EL, Clyde MA, Iversen ES, Moorman PG, Berchuck A, Marks JR, Lissowska J, Brinton L, Peplonska B, Cunningham JM, Vierkant RA, Rider DN, Chenevix-Trench G, Webb PM, Beesley J, Chen X, Phelan C, Sutphen R, Sellers TA, Pearce L, Wu AH, Van Den Berg D, Conti D, Elund CK, Anderson R, Goodman MT, Lurie G, Carney ME, Thompson PJ, Gayther SA, Ramus SJ, Jacobs I, Krüger Kjaer S, Hogdall E, Blaakaer J, Hogdall C, Easton DF, Song H, Pharoah PD, Whittemore AS, McGuire V, Quaye L, Anton-Culver H, Ziogas A, Terry KL, Cramer DW, Hankinson SE, Tworoger SS, Calingaert B, Chanock S, Sherman M, Garcia-Closas M, Australian Ovarian Cancer Study Group
Source: Cancer Res, 2009 Mar 15;69(6), p. 2349-57.
EPub date: 2009 Mar 10.
PMID: 19276375
Related Citations

Back to top


Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.
Authors: Setiawan VW, Doherty JA, Shu XO, Akbari MR, Chen C, De Vivo I, Demichele A, Garcia-Closas M, Goodman MT, Haiman CA, Hankinson SE, Henderson BE, Horn-Ross PL, Lacey JV Jr, Le Marchand L, Levine DA, Liang X, Lissowska J, Lurie G, McGrath M, Narod SA, Rebbeck TR, Ursin G, Weiss NS, Xiang YB, Yang HP, Zheng W, Olson SH
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jan;18(1), p. 242-7.
PMID: 19124504
Related Citations

Back to top


Genetic polymorphisms in the Paraoxonase 1 gene and risk of ovarian epithelial carcinoma.
Authors: Lurie G, Wilkens LR, Thompson PJ, McDuffie KE, Carney ME, Terada KY, Goodman MT
Source: Cancer Epidemiol Biomarkers Prev, 2008 Aug;17(8), p. 2070-7.
PMID: 18708400
Related Citations

Back to top


Consortium analysis of 7 candidate SNPs for ovarian cancer.
Authors: Ramus SJ, Vierkant RA, Johnatty SE, Pike MC, Van Den Berg DJ, Wu AH, Pearce CL, Menon U, Gentry-Maharaj A, Gayther SA, Dicioccio RA, McGuire V, Whittemore AS, Song H, Easton DF, Pharoah PD, Garcia-Closas M, Chanock S, Lissowska J, Brinton L, Terry KL, Cramer DW, Tworoger SS, Hankinson SE, Berchuck A, Moorman PG, Schildkraut JM, Cunningham JM, Liebow M, Kjaer SK, Hogdall E, Hogdall C, Blaakaer J, Ness RB, Moysich KB, Edwards RP, Carney ME, Lurie G, Goodman MT, Wang-Gohrke S, Kropp S, Chang-Claude J, Australian Ovarian Cancer Study Group, Australian Cancer Study (Ovarian Cancer), Webb PM, Chen X, Beesley J, Chenevix-Trench G, Goode EL, Ovarian Cancer Association Consortium
Source: Int J Cancer, 2008 Jul 15;123(2), p. 380-8.
PMID: 18431743
Related Citations

Back to top


An oncolytic adenovirus vector combining enhanced cell-to-cell spreading, mediated by the ADP cytolytic protein, with selective replication in cancer cells with deregulated wnt signaling.
Authors: Toth K, Djeha H, Ying B, Tollefson AE, Kuppuswamy M, Doronin K, Krajcsi P, Lipinski K, Wrighton CJ, Wold WS
Source: Cancer Res, 2004 May 15;64(10), p. 3638-44.
PMID: 15150123
Related Citations

Back to top