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Grant Details

Grant Number: 7R01CA100598-05 Interpret this number
Primary Investigator: Ambrosone, Christine
Organization: Roswell Park Cancer Institute Corp
Project Title: Race & Risk Factors for Early/Aggressive Breast Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): Breast cancer in African-American women occurs at an earlier age than in Caucasian women and is more likely to have aggressive features associated with poorer prognosis, regardless of age at diagnosis. The mechanisms underlying these differences are as yet unknown. Although factors related to socioeconomic status (SES) are likely to play a role in racial differences in stage at diagnosis and disease-free survival, SES factors are unlikely to fully explain the earlier age at diagnosis or the more aggressive nature of breast cancer in African-American women. Most recognized risk factors for breast cancer involve reproductive or hormonal characteristics. Importantly, there are notable differences between African-Americans and Caucasians in distribution of polymorphisms in genes that govern steroid biosynthesis and metabolism, in endogenous hormone profiles, and in menstrual and childbearing histories. These risk factor differences could impact breast cancer in African-American and Caucasian women, although the potential role of SES factors cannot be discounted. To our knowledge, there have been no studies specifically designed and with adequate power to address these questions. Building upon a funded case-control study of bio-behavioral risk factors for breast cancer in African-American women, we propose to investigate determinants of early age at onset and high grade, ER negative disease among African-Americans and Caucasians and to evaluate the proportion of disparities in aggressive disease that can be accounted for by differential distribution of genetic and hormonally-related risk factors in both racial groups. We intend to enroll 1200 Caucasian cases and 1200 controls and to enroll an additional 800 African-American women. We will over-enroll women under age 50 so that we will have equal proportions of younger and older women in both racial groups. Combined with data from the ongoing study, the proposed study will include 1200 African-American women with breast cancer and 1200 controls and an equal number of Caucasians. We hypothesize that factors associated with higher exposures to circulating estrogens, as well as the timing of those exposures, including early age at menarche, early and multiple pregnancies, energy balance and body size, as well as polymorphisms that result in higher active hormone levels will be associated with early age at diagnosis and high-grade, ER negative breast cancer, and that these factors will be more prevalent among African-American than Caucasian women. We will also examine the role of socio-economic factors, including screening behaviors and access to care, in the higher prevalence of high-grade, ER- tumors among African-American women. Results from this study will provide much-needed answers as to why African-American women are more likely than Caucasians to be diagnosed with more aggressive disease at an earlier age.

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Publications

Non-initiation and early discontinuation of adjuvant trastuzumab in women with localized HER2-positive breast cancer.
Authors: Neugut AI, Hillyer GC, Kushi LH, Lamerato L, Leoce N, Ambrosone CB, Bovbjerg DH, Mandelblatt JS, Hershman DL
Source: Breast Cancer, 2014 Jun 6;null, p. null.
EPub date: 2014 Jun 6.
PMID: 24902664
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Associations between estrogen receptor-negative breast cancer and timing of reproductive events differ between African American and European American women.
Authors: Ambrosone CB, Zirpoli GR, Bovbjerg DH, Shankar J, Hong CC, McCann SE, Ruszczyk M, Khoury T, Yao S, Ciupak GL, Jandorf L, Pawlish KS, Bandera EV
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jun;23(6), p. 1115-20.
EPub date: 2014 Apr 9.
PMID: 24718280
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Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women's Circle of Health Study.
Authors: Ambrosone CB, Zirpoli G, Ruszczyk M, Shankar J, Hong CC, McIlwain D, Roberts M, Yao S, McCann SE, Ciupak G, Hwang H, Khoury T, Jandorf L, Bovbjerg DH, Pawlish K, Bandera EV
Source: Cancer Causes Control, 2014 Feb;25(2), p. 259-65.
EPub date: 2013 Nov 19.
PMID: 24249438
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Body fatness and breast cancer risk in women of African ancestry.
Authors: Bandera EV, Chandran U, Zirpoli G, Gong Z, McCann SE, Hong CC, Ciupak G, Pawlish K, Ambrosone CB
Source: BMC Cancer, 2013 Oct 14;13, p. 475.
EPub date: 2013 Oct 14.
PMID: 24118876
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Body size in early life and breast cancer risk in African American and European American women.
Authors: Bandera EV, Chandran U, Zirpoli G, Ciupak G, Bovbjerg DH, Jandorf L, Pawlish K, Freudenheim JL, Ambrosone CB
Source: Cancer Causes Control, 2013 Dec;24(12), p. 2231-43.
EPub date: 2013 Oct 10.
PMID: 24113797
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Racial disparities in red meat and poultry intake and breast cancer risk.
Authors: Chandran U, Zirpoli G, Ciupak G, McCann SE, Gong Z, Pawlish K, Lin Y, Demissie K, Ambrosone CB, Bandera EV
Source: Cancer Causes Control, 2013 Dec;24(12), p. 2217-29.
EPub date: 2013 Oct 5.
PMID: 24091794
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Genetic variants in microRNAs and breast cancer risk in African American and European American women.
Authors: Yao S, Graham K, Shen J, Campbell LE, Singh P, Zirpoli G, Roberts M, Ciupak G, Davis W, Hwang H, Khoury T, Bovbjerg DH, Jandorf L, Pawlish KS, Bandera EV, Liu S, Ambrosone CB, Zhao H
Source: Breast Cancer Res Treat, 2013 Oct;141(3), p. 447-59.
EPub date: 2013 Sep 24.
PMID: 24062209
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Does alcohol increase breast cancer risk in African-American women? Findings from a case-control study.
Authors: Chandran U, Zirpoli G, Ciupak G, McCann SE, Gong Z, Pawlish K, Lin Y, Demissie K, Ambrosone CB, Bandera EV
Source: Br J Cancer, 2013 Oct 1;109(7), p. 1945-53.
EPub date: 2013 Sep 5.
PMID: 24008665
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Associations of dietary folate, Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women.
Authors: Gong Z, Ambrosone CB, McCann SE, Zirpoli G, Chandran U, Hong CC, Bovbjerg DH, Jandorf L, Ciupak G, Pawlish K, Lu Q, Hwang H, Khoury T, Wiam B, Bandera EV
Source: Int J Cancer, 2014 Mar 15;134(6), p. 1422-35.
EPub date: 2013 Sep 30.
PMID: 23996837
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Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry.
Authors: Quan L, Gong Z, Yao S, Bandera EV, Zirpoli G, Hwang H, Roberts M, Ciupak G, Davis W, Sucheston L, Pawlish K, Bovbjerg DH, Jandorf L, Cabasag C, Coignet JG, Ambrosone CB, Hong CC
Source: Int J Cancer, 2014 Mar 15;134(6), p. 1408-21.
EPub date: 2013 Oct 8.
PMID: 23996684
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Innate immunity pathways and breast cancer Risk in African American and European-American women in the Women's Circle of Health Study (WCHS).
Authors: Gong Z, Quan L, Yao S, Zirpoli G, Bandera EV, Roberts M, Coignet JG, Cabasag C, Sucheston L, Hwang H, Ciupak G, Davis W, Pawlish K, Jandorf L, Bovbjerg DH, Ambrosone CB, Hong CC
Source: PLoS One, 2013;8(8), p. e72619.
EPub date: 2013 Aug 21.
PMID: 23991131
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Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Authors: Liu CT, Monda KL, Taylor KC, Lange L, Demerath EW, Palmas W, Wojczynski MK, Ellis JC, Vitolins MZ, Liu S, Papanicolaou GJ, Irvin MR, Xue L, Griffin PJ, Nalls MA, Adeyemo A, Liu J, Li G, Ruiz-Narvaez EA, Chen WM, Chen F, Henderson BE, Millikan RC, Ambrosone CB, Strom SS, Guo X, Andrews JS, Sun YV, Mosley TH, Yanek LR, Shriner D, Haritunians T, Rotter JI, Speliotes EK, Smith M, Rosenberg L, Mychaleckyj J, Nayak U, Spruill I, Garvey WT, Pettaway C, Nyante S, Bandera EV, Britton AF, Zonderman AB, Rasmussen-Torvik LJ, Chen YD, Ding J, Lohman K, Kritchevsky SB, Zhao W, Peyser PA, Kardia SL, Kabagambe E, Broeckel U, Chen G, Zhou J, Wassertheil-Smoller S, Neuhouser ML, Rampersaud E, Psaty B, Kooperberg C, Manson JE, Kuller LH, Ochs-Balcom HM, Johnson KC, Sucheston L, Ordovas JM, Palmer JR, Haiman CA, McKnight B, Howard BV, Becker DM, Bielak LF, Liu Y, Allison MA, Grant SF, Burke GL, Patel SR, Schreiner PJ, Borecki IB, Evans MK, Taylor H, Sale MM, Howard V, Carlson CS, Rotimi CN, Cushman M, Harris TB, Reiner AP, Cupples LA, North KE, Fox CS
Source: PLoS Genet, 2013;9(8), p. e1003681.
EPub date: 2013 Aug 15.
PMID: 23966867
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Rethinking sources of representative controls for the conduct of case-control studies in minority populations.
Authors: Bandera EV, Chandran U, Zirpoli G, McCann SE, Ciupak G, Ambrosone CB
Source: BMC Med Res Methodol, 2013 May 31;13, p. 71.
EPub date: 2013 May 31.
PMID: 23721229
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Genome-wide association study of age at menarche in African-American women.
Authors: Demerath EW, Liu CT, Franceschini N, Chen G, Palmer JR, Smith EN, Chen CT, Ambrosone CB, Arnold AM, Bandera EV, Berenson GS, Bernstein L, Britton A, Cappola AR, Carlson CS, Chanock SJ, Chen W, Chen Z, Deming SL, Elks CE, Evans MK, Gajdos Z, Henderson BE, Hu JJ, Ingles S, John EM, Kerr KF, Kolonel LN, Le Marchand L, Lu X, Millikan RC, Musani SK, Nock NL, North K, Nyante S, Press MF, Rodriquez-Gil JL, Ruiz-Narvaez EA, Schork NJ, Srinivasan SR, Woods NF, Zheng W, Ziegler RG, Zonderman A, Heiss G, Gwen Windham B, Wellons M, Murray SS, Nalls M, Pastinen T, Rajkovic A, Hirschhorn J, Adrienne Cupples L, Kooperberg C, Murabito JM, Haiman CA
Source: Hum Mol Genet, 2013 Aug 15;22(16), p. 3329-46.
EPub date: 2013 Apr 17.
PMID: 23599027
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda KL, Chen GK, Taylor KC, Palmer C, Edwards TL, Lange LA, Ng MC, Adeyemo AA, Allison MA, Bielak LF, Chen G, Graff M, Irvin MR, Rhie SK, Li G, Liu Y, Liu Y, Lu Y, Nalls MA, Sun YV, Wojczynski MK, Yanek LR, Aldrich MC, Ademola A, Amos CI, Bandera EV, Bock CH, Britton A, Broeckel U, Cai Q, Caporaso NE, Carlson CS, Carpten J, Casey G, Chen WM, Chen F, Chen YD, Chiang CW, Coetzee GA, Demerath E, Deming-Halverson SL, Driver RW, Dubbert P, Feitosa MF, Feng Y, Freedman BI, Gillanders EM, Gottesman O, Guo X, Haritunians T, Harris T, Harris CC, Hennis AJ, Hernandez DG, McNeill LH, Howard TD, Howard BV, Howard VJ, Johnson KC, Kang SJ, Keating BJ, Kolb S, Kuller LH, Kutlar A, Langefeld CD, Lettre G, Lohman K, Lotay V, Lyon H, Manson JE, Maixner W, Meng YA, Monroe KR, Morhason-Bello I, Murphy AB, Mychaleckyj JC, Nadukuru R, Nathanson KL, Nayak U, N'diaye A, Nemesure B, Wu SY, Leske MC, Neslund-Dudas C, Neuhouser M, Nyante S, Ochs-Balcom H, Ogunniyi A, Ogundiran TO, Ojengbede O, Olopade OI, Palmer JR, Ruiz-Narvaez EA, Palmer ND, Press MF, Rampersaud E, Rasmussen-Torvik LJ, Rodriguez-Gil JL, Salako B, Schadt EE, Schwartz AG, Shriner DA, Siscovick D, Smith SB, Wassertheil-Smoller S, Speliotes EK, Spitz MR, Sucheston L, Taylor H, Tayo BO, Tucker MA, Van Den Berg DJ, Edwards DR, Wang Z, Wiencke JK, Winkler TW, Witte JS, Wrensch M, Wu X, Yang JJ, Levin AM, Young TR, Zakai NA, Cushman M, Zanetti KA, Zhao JH, Zhao W, Zheng Y, Zhou J, Ziegler RG, Zmuda JM, Fernandes JK, Gilkeson GS, Kamen DL, Hunt KJ, Spruill IJ, Ambrosone CB, Ambs S, Arnett DK, Atwood L, Becker DM, Berndt SI, Bernstein L, Blot WJ, Borecki IB, Bottinger EP, Bowden DW, Burke G, Chanock SJ, Cooper RS, Ding J, Duggan D, Evans MK, Fox C, Garvey WT, Bradfield JP, Hakonarson H, Grant SF, Hsing A, Chu L, Hu JJ, Huo D, Ingles SA, John EM, Jordan JM, Kabagambe EK, Kardia SL, Kittles RA, Goodman PJ, Klein EA, Kolonel LN, Le Marchand L, Liu S, McKnight B, Millikan RC, Mosley TH, Padhukasahasram B, Williams LK, Patel SR, Peters U, Pettaway CA, Peyser PA, Psaty BM, Redline S, Rotimi CN, Rybicki BA, Sale MM, Schreiner PJ, Signorello LB, Singleton AB, Stanford JL, Strom SS, Thun MJ, Vitolins M, Zheng W, Moore JH, Williams SM, Ketkar S, Zhu X, Zonderman AB, NABEC Consortium, UKBEC Consortium, BioBank Japan Project, AGEN Consortium, Kooperberg C, Papanicolaou GJ, Henderson BE, Reiner AP, Hirschhorn JN, Loos RJ, North KE, Haiman CA
Source: Nat Genet, 2013 Jun;45(6), p. 690-6.
EPub date: 2013 Apr 14.
PMID: 23583978
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Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
Authors: Garcia-Closas M, Couch FJ, Lindstrom S, Michailidou K, Schmidt MK, Brook MN, Orr N, Rhie SK, Riboli E, Feigelson HS, Le Marchand L, Buring JE, Eccles D, Miron P, Fasching PA, Brauch H, Chang-Claude J, Carpenter J, Godwin AK, Nevanlinna H, Giles GG, Cox A, Hopper JL, Bolla MK, Wang Q, Dennis J, Dicks E, Howat WJ, Schoof N, Bojesen SE, Lambrechts D, Broeks A, Andrulis IL, Guénel P, Burwinkel B, Sawyer EJ, Hollestelle A, Fletcher O, Winqvist R, Brenner H, Mannermaa A, Hamann U, Meindl A, Lindblom A, Zheng W, Devillee P, Goldberg MS, Lubinski J, Kristensen V, Swerdlow A, Anton-Culver H, Dörk T, Muir K, Matsuo K, Wu AH, Radice P, Teo SH, Shu XO, Blot W, Kang D, Hartman M, Sangrajrang S, Shen CY, Southey MC, Park DJ, Hammet F, Stone J, Veer LJ, Rutgers EJ, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Peto J, Schrauder MG, Ekici AB, Beckmann MW, Dos Santos Silva I, Johnson N, Warren H, Tomlinson I, Kerin MJ, Miller N, Marme F, Schneeweiss A, Sohn C, Truong T, Laurent-Puig P, Kerbrat P, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Perez JI, Menéndez P, Müller H, Arndt V, Stegmaier C, Lichtner P, Lochmann M, Justenhoven C, Ko YD, Gene ENvironmental Interaction and breast CAncer (GENICA) Network, Muranen TA, Aittomäki K, Blomqvist C, Greco D, Heikkinen T, Ito H, Iwata H, Yatabe Y, Antonenkova NN, Margolin S, Kataja V, Kosma VM, Hartikainen JM, Balleine R, kConFab Investigators, Tseng CC, Berg DV, Stram DO, Neven P, Dieudonné AS, Leunen K, Rudolph A, Nickels S, Flesch-Janys D, Peterlongo P, Peissel B, Bernard L, Olson JE, Wang X, Stevens K, Severi G, Baglietto L, McLean C, Coetzee GA, Feng Y, Henderson BE, Schumacher F, Bogdanova NV, Labrčche F, Dumont M, Yip CH, Taib NA, Cheng CY, Shrubsole M, Long J, Pylkäs K, Jukkola-Vuorinen A, Kauppila S, Knight JA, Glendon G, Mulligan AM, Tollenaar RA, Seynaeve CM, Kriege M, Hooning MJ, van den Ouweland AM, van Deurzen CH, Lu W, Gao YT, Cai H, Balasubramanian SP, Cross SS, Reed MW, Signorello L, Cai Q, Shah M, Miao H, Chan CW, Chia KS, Jakubowska A, Jaworska K, Durda K, Hsiung CN, Wu PE, Yu JC, Ashworth A, Jones M, Tessier DC, González-Neira A, Pita G, Alonso MR, Vincent D, Bacot F, Ambrosone CB, Bandera EV, John EM, Chen GK, Hu JJ, Rodriguez-Gil JL, Bernstein L, Press MF, Ziegler RG, Millikan RM, Deming-Halverson SL, Nyante S, Ingles SA, Waisfisz Q, Tsimiklis H, Makalic E, Schmidt D, Bui M, Gibson L, Müller-Myhsok B, Schmutzler RK, Hein R, Dahmen N, Beckmann L, Aaltonen K, Czene K, Irwanto A, Liu J, Turnbull C, Familial Breast Cancer Study (FBCS), Rahman N, Meijers-Heijboer H, Uitterlinden AG, Rivadeneira F, Australian Breast Cancer Tissue Bank (ABCTB) Investigators, Olswold C, Slager S, Pilarski R, Ademuyiwa F, Konstantopoulou I, Martin NG, Montgomery GW, Slamon DJ, Rauh C, Lux MP, Jud SM, Bruning T, Weaver J, Sharma P, Pathak H, Tapper W, Gerty S, Durcan L, Trichopoulos D, Tumino R, Peeters PH, Kaaks R, Campa D, Canzian F, Weiderpass E, Johansson M, Khaw KT, Travis R, Clavel-Chapelon F, Kolonel LN, Chen C, Beck A, Hankinson SE, Berg CD, Hoover RN, Lissowska J, Figueroa JD, Chasman DI, Gaudet MM, Diver WR, Willett WC, Hunter DJ, Simard J, Benitez J, Dunning AM, Sherman ME, Chenevix-Trench G, Chanock SJ, Hall P, Pharoah PD, Vachon C, Easton DF, Haiman CA, Kraft P
Source: Nat Genet, 2013 Apr;45(4), p. 392-8, 398e1-2.
PMID: 23535733
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A genome-wide scan for breast cancer risk haplotypes among African American women.
Authors: Song C, Chen GK, Millikan RC, Ambrosone CB, John EM, Bernstein L, Zheng W, Hu JJ, Ziegler RG, Nyante S, Bandera EV, Ingles SA, Press MF, Deming SL, Rodriguez-Gil JL, Chanock SJ, Wan P, Sheng X, Pooler LC, Van Den Berg DJ, Le Marchand L, Kolonel LN, Henderson BE, Haiman CA, Stram DO
Source: PLoS One, 2013;8(2), p. e57298.
EPub date: 2013 Feb 28.
PMID: 23468962
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Racial disparities in posttraumatic stress after diagnosis of localized breast cancer: the BQUAL study.
Authors: Vin-Raviv N, Hillyer GC, Hershman DL, Galea S, Leoce N, Bovbjerg DH, Kushi LH, Kroenke C, Lamerato L, Ambrosone CB, Valdimorsdottir H, Jandorf L, Mandelblatt JS, Tsai WY, Neugut AI
Source: J Natl Cancer Inst, 2013 Apr 17;105(8), p. 563-72.
EPub date: 2013 Feb 21.
PMID: 23434900
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Interpersonal influences and attitudes about adjuvant therapy treatment decisions among non-metastatic breast cancer patients: an examination of differences by age and race/ethnicity in the BQUAL study.
Authors: Shelton RC, Clarke Hillyer G, Hershman DL, Leoce N, Bovbjerg DH, Mandelblatt JS, Kushi LH, Lamerato L, Nathanson SD, Ambrosone CB, Neugut AI
Source: Breast Cancer Res Treat, 2013 Feb;137(3), p. 817-28.
EPub date: 2012 Dec 22.
PMID: 23263696
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A survey of breast cancer physicians regarding patient involvement in breast cancer treatment decisions.
Authors: Hillyer GC, Hershman DL, Kushi LH, Lamerato L, Ambrosone CB, Bovbjerg DH, Mandelblatt JS, Rana S, Neugut AI
Source: Breast, 2013 Aug;22(4), p. 548-54.
EPub date: 2012 Oct 27.
PMID: 23107518
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Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women.
Authors: Ruiz-Narváez EA, Rosenberg L, Yao S, Rotimi CN, Cupples AL, Bandera EV, Ambrosone CB, Adams-Campbell LL, Palmer JR
Source: Carcinogenesis, 2013 Feb;34(2), p. 287-91.
EPub date: 2012 Oct 26.
PMID: 23104177
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Noninitiation of adjuvant chemotherapy in women with localized breast cancer: the breast cancer quality of care study.
Authors: Neugut AI, Hillyer GC, Kushi LH, Lamerato L, Leoce N, Nathanson SD, Ambrosone CB, Bovbjerg DH, Mandelblatt JS, Magai C, Tsai WY, Jacobson JS, Hershman DL
Source: J Clin Oncol, 2012 Nov 1;30(31), p. 3800-9.
EPub date: 2012 Sep 24.
PMID: 23008305
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