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Grant Details

Grant Number: 5R01CA105212-04 Interpret this number
Primary Investigator: Chen, Chu
Organization: Fred Hutchinson Cancer Research Center
Project Title: Molecular Epidemiology of Endometrial Cancer
Fiscal Year: 2007
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Abstract

DESCRIPTION (provided by applicant): It is well established that estrogen exposure increases the risk of endometrial cancer. However, the presence or absence of currently known risk factors for this disease, such as the use of unopposed estrogens or obesity, offers little sensitivity or specificity in predicting which women will go on to develop it. We propose to test the hypotheses that the risk of developing endometrial cancer is related to variation in genes that encode for enzymes: 1) involved in the biosynthesis or catabolism of estrogens, or in the response to steroid hormones, and 2) that repair DNA damage generated during estrogen exposure. A population-based case-control study of 803 endometrial cancer cases and 753 controls ages 50-74 years will be conducted in three counties of Western Washington State. This study will build upon our previous case-control study of endometrial cancer (cases=383, controls=450). We will recruit an additional 420 incident cases, diagnosed between 7/03-12/05, who are identified through a population-based cancer registry that is part of the Surveillance, Epidemiology and End Results program, and will use a subset of controls (n=303), identified through random-digit dialing from an ongoing ovarian cancer study. These controls will have intact uteri, and will be similar to the cases in terms of geographic area and age. Cases and controls will be interviewed in person regarding lifestyle and medical history, and a venous blood sample will be obtained. Genomic DNA will be tested for variants in genes involved in 1) the synthesis, catabolism, and response to estrogens; and 2) base excision repair of oxidative DNA damage and nucleotide excision repair of DNA damage caused by bulky adducts. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes and results will be interpreted with multiple comparisons taken into account. The proposed study has sufficient statistical power to identify interactions between some of the high-risk genotypes, and to investigate whether the risk associated with some of the genotypes varies by other risk factors, such as exposure to exogenous hormones and obesity. Efforts will also be devoted to generating risk indices through statistical modeling that integrate potential effects of genetic variants in the estrogen metabolism pathway and/or DNA repair pathways.

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Publications

Exome-wide association study of endometrial cancer in a multiethnic population.
Authors: Chen MM, Crous-Bou M, Setiawan VW, Prescott J, Olson SH, Wentzensen N, Black A, Brinton L, Chen C, Chen C, Cook LS, Doherty J, Friedenreich CM, Hankinson SE, Hartge P, Henderson BE, Hunter DJ, Le Marchand L, Liang X, Lissowska J, Lu L, Orlow I, Petruzella S, Polidoro S, Pooler L, Rebbeck TR, Risch H, Sacerdote C, Schumacher F, Sheng X, Shu XO, Weiss NS, Xia L, Van Den Berg D, Yang HP, Yu H, Chanock S, Haiman C, Kraft P, De Vivo I
Source: PLoS One, 2014;9(5), p. e97045.
EPub date: 2014 May 8.
PMID: 24810602
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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
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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
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Long-term use of continuous-combined estrogen-progestin hormone therapy and risk of endometrial cancer.
Authors: Phipps AI, Doherty JA, Voigt LF, Hill DA, Beresford SA, Rossing MA, Chen C, Weiss NS
Source: Cancer Causes Control, 2011 Dec;22(12), p. 1639-46.
EPub date: 2011 Sep 11.
PMID: 21909949
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Polymorphisms in nucleotide excision repair genes and endometrial cancer risk.
Authors: Doherty JA, Weiss NS, Fish S, Fan W, Loomis MM, Sakoda LC, Rossing MA, Zhao LP, Chen C
Source: Cancer Epidemiol Biomarkers Prev, 2011 Sep;20(9), p. 1873-82.
EPub date: 2011 Jul 12.
PMID: 21750170
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Pregnancy history and risk of endometrial cancer.
Authors: Pocobelli G, Doherty JA, Voigt LF, Beresford SA, Hill DA, Chen C, Rossing MA, Holmes RS, Noor ZS, Weiss NS
Source: Epidemiology, 2011 Sep;22(5), p. 638-45.
PMID: 21691206
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The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.
Authors: Lurie G, Gaudet MM, Spurdle AB, Carney ME, Wilkens LR, Yang HP, Weiss NS, Webb PM, Thompson PJ, Terada K, Setiawan VW, Rebbeck TR, Prescott J, Orlow I, O'Mara T, Olson SH, Narod SA, Matsuno RK, Lissowska J, Liang X, Levine DA, Le Marchand L, Kolonel LN, Henderson BE, Garcia-Closas M, Doherty JA, De Vivo I, Chen C, Brinton LA, Akbari MR, Australian National Endometrial Cancer Study Group, Epidemiology of Endometrial Cancer Consortium (E2C2), Goodman MT
Source: PLoS One, 2011 Feb 8;6(2), p. e16756.
EPub date: 2011 Feb 8.
PMID: 21347432
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Use of nonsteroidal antiinflammatory drugs and risk of endometrial cancer.
Authors: Bodelon C, Doherty JA, Chen C, Rossing MA, Weiss NS
Source: Am J Epidemiol, 2009 Dec 15;170(12), p. 1512-7.
EPub date: 2009 Nov 6.
PMID: 19897512
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Maximizing resources to study an uncommon cancer: E2C2--Epidemiology of Endometrial Cancer Consortium.
Authors: Olson SH, Chen C, De Vivo I, Doherty JA, Hartmuller V, Horn-Ross PL, Lacey JV Jr, Lynch SM, Sansbury L, Setiawan VW, Schouten LJ, Shu XO
Source: Cancer Causes Control, 2009 May;20(4), p. 491-6.
EPub date: 2009 Jan 9.
PMID: 19132539
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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
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Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer.
Authors: Doherty JA, Cushing-Haugen KL, Saltzman BS, Voigt LF, Hill DA, Beresford SA, Chen C, Weiss NS
Source: Am J Obstet Gynecol, 2007 Aug;197(2), p. 139.e1-7.
PMID: 17689625
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Endometrial cancer risk in estrogen users after switching to estrogen-progestin therapy.
Authors: Chubak J, Doherty JA, Cushing-Haugen KL, Voigt LF, Saltzman BS, Hill DA, Beresford SA, Weiss NS
Source: Cancer Causes Control, 2007 Nov;18(9), p. 1001-7.
EPub date: 2007 Jul 25.
PMID: 17653829
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Nucleotide excision repair genotype and the incidence of endometrial cancer: effect of other risk factors on the association.
Authors: Weiss JM, Weiss NS, Ulrich CM, Doherty JA, Chen C
Source: Gynecol Oncol, 2006 Dec;103(3), p. 891-6.
EPub date: 2006 Jun 23.
PMID: 16806437
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Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer.
Authors: Weiss JM, Weiss NS, Ulrich CM, Doherty JA, Voigt LF, Chen C
Source: Cancer Epidemiol Biomarkers Prev, 2005 Nov;14(11 Pt 1), p. 2524-30.
PMID: 16284373
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