{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:24:36Z","timestamp":1789741476633,"version":"4.0.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2008,7,8]],"date-time":"2008-07-08T00:00:00Z","timestamp":1215475200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2008,7,8]],"date-time":"2008-07-08T00:00:00Z","timestamp":1215475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Obesity has consistently been associated with postmenopausal breast cancer risk. Proteins that are secreted by adipose tissue or are involved in regulating body mass may play a role in breast tumor development.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We conducted a nested case-control study among postmenopausal women from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to determine whether genes associated with obesity increase risk for breast cancer. Tagging single nucleotide polymorphisms (SNPs) were selected to capture common variation across seven candidate genes that encode adipose-related proteins: <jats:italic>ADRB2<\/jats:italic>, <jats:italic>ADRB3<\/jats:italic>, <jats:italic>GHRL<\/jats:italic>, <jats:italic>HSD11B1<\/jats:italic>, <jats:italic>IRS1<\/jats:italic>, <jats:italic>IRS2<\/jats:italic>, and <jats:italic>SHC1<\/jats:italic>. Thirty-nine SNPs were genotyped in 648 cases and 659 controls. Logistic regression models were used to examine the association between each tagging SNP and risk for breast cancer while adjusting for matching factors and potential confounders. We also examined whether these SNPs were associated with measures of adult adiposity.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Two out of five tagging SNPs in <jats:italic>HSD11B1<\/jats:italic> were associated with breast cancer (rs11807619, <jats:italic>P<\/jats:italic> = 0.006; rs932335, <jats:italic>P<\/jats:italic> = 0.0001). rs11807619 and rs932335 were highly correlated (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> = 0.74) and, when modeled as a haplotype, only haplotypes containing the rs932335 C allele were associated with breast cancer. The rs932335 C allele was associated with a nearly twofold increased risk for breast cancer (odds ratio = 1.83, 95% confidence interval = 1.01\u20133.33 for C\/C versus G\/G). Three of the 11 SNPs for <jats:italic>IRS2<\/jats:italic> were associated with breast cancer (rs4773082, <jats:italic>P<\/jats:italic> = 0.007; rs2289046, <jats:italic>P<\/jats:italic> = 0.016; rs754204, <jats:italic>P<\/jats:italic> = 0.03). When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63\u20130.92 for TGC versus CAT). <jats:italic>IRS2<\/jats:italic> rs2289046, rs754204, and rs12584136 were also associated with adult weight gain but only among cases. None of the other SNPs in any gene investigated were associated with breast cancer or adiposity.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Our findings suggest that these tagging SNPs in <jats:italic>HSD11B1<\/jats:italic> and <jats:italic>IRS2<\/jats:italic> mark regions of the genome that may harbor risk alleles for breast cancer, and these associations are probably independent of adiposity.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr2114","type":"journal-article","created":{"date-parts":[[2008,7,23]],"date-time":"2008-07-23T18:14:00Z","timestamp":1216836840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II"],"prefix":"10.1186","volume":"10","author":[{"given":"Heather Spencer","family":"Feigelson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren R","family":"Teras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Ryan","family":"Diver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weining","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpa V","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia E","family":"Calle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Thun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Bouzyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,7,8]]},"reference":[{"key":"2078_CR1","volume-title":"Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective","author":"World Cancer Research Fund","year":"2007","unstructured":"World Cancer Research Fund: Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. 2007, Washington, DC: AICR"},{"key":"2078_CR2","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nrc1408","volume":"4","author":"E Calle","year":"2004","unstructured":"Calle E, Kaaks R: Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Reviews Cancer. 2004, 4: 579-591. 10.1038\/nrc1408.","journal-title":"Nature Reviews Cancer"},{"key":"2078_CR3","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/cncr.21965","volume":"107","author":"HS Feigelson","year":"2006","unstructured":"Feigelson HS, Patel AV, Teras LR, Gansler T, Thun MJ, Calle EE: Adult weight gain and histopathologic characteristics of breast cancer among postmenopausal women. Cancer. 2006, 107: 12-21. 10.1002\/cncr.21965.","journal-title":"Cancer"},{"key":"2078_CR4","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1093\/jnci\/87.17.1297","volume":"87","author":"SE Hankinson","year":"1995","unstructured":"Hankinson SE, Willett WC, Manson JE, Hunter DJ, Colditz GA, Stampfer MJ, Longcope C, Speizer FE: Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer Inst. 1995, 87: 1297-1302. 10.1093\/jnci\/87.17.1297.","journal-title":"J Natl Cancer Inst"},{"key":"2078_CR5","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1093\/jnci\/88.11.756","volume":"88","author":"N Potischman","year":"1996","unstructured":"Potischman N, Swanson C, Siiteri P, Hoover R: Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst. 1996, 88: 756-758. 10.1093\/jnci\/88.11.756.","journal-title":"J Natl Cancer Inst"},{"key":"2078_CR6","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/bcr304","volume":"3","author":"XE Huang","year":"2001","unstructured":"Huang XE, Hamajima N, Saito T, Matsuo K, Mizutani M, Iwata H, Iwase T, Miura S, Mizuno T, Tokudome S, Tajima K: Possible association of beta2- and beta3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer. Breast Cancer Res. 2001, 3: 264-269. 10.1186\/bcr304.","journal-title":"Breast Cancer Res"},{"key":"2078_CR7","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1038\/sj.ijo.0803554","volume":"31","author":"R McKean-Cowdin","year":"2007","unstructured":"McKean-Cowdin R, Li X, Bernstein L, McTiernan A, Ballard-Barbash R, Gauderman WJ, Gilliland F: The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases. Int J Obes (Lond). 2007, 31: 1110-1118. 10.1038\/sj.ijo.0803554.","journal-title":"Int J Obes (Lond)"},{"key":"2078_CR8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s10549-006-9403-9","volume":"104","author":"ML Slattery","year":"2007","unstructured":"Slattery ML, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, Byers T: Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat. 2007, 104: 197-209. 10.1007\/s10549-006-9403-9.","journal-title":"Breast Cancer Res Treat"},{"key":"2078_CR9","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1093\/carcin\/bgl036","volume":"27","author":"K Wagner","year":"2006","unstructured":"Wagner K, Hemminki K, Grzybowska E, Klaes R, Burwinkel B, Bugert P, Schmutzler RK, Wappenschmidt B, Butkiewicz D, Pamula J, Pekala W, F\u00f6rsti A: Polymorphisms in genes involved in GH1 release and their association with breast cancer risk. Carcinogenesis. 2006, 27: 1867-1875. 10.1093\/carcin\/bgl036.","journal-title":"Carcinogenesis"},{"key":"2078_CR10","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1093\/carcin\/bgh263","volume":"25","author":"K Wagner","year":"2004","unstructured":"Wagner K, Hemminki K, Grzybowska E, Klaes R, Butkiewicz D, Pamula J, Pekala W, Zientek H, Mielzynska D, Siwinska E, F\u00f6rsti A: The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer. Carcinogenesis. 2004, 25: 2473-2478. 10.1093\/carcin\/bgh263.","journal-title":"Carcinogenesis"},{"key":"2078_CR11","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1158\/1055-9965.1206.13.7","volume":"13","author":"ML Slattery","year":"2004","unstructured":"Slattery ML, Samowitz W, Curtin K, Ma KN, Hoffman M, Caan B, Neuhausen S: Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2004, 13: 1206-1214.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2078_CR12","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1158\/1055-9965.EPI-04-0895","volume":"14","author":"DR Skibola","year":"2005","unstructured":"Skibola DR, Smith MT, Bracci PM, Hubbard AE, Agana L, Chi S, Holly EA: Polymorphisms in ghrelin and neuropeptide Y genes are associated with non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1251-1256. 10.1158\/1055-9965.EPI-04-0895.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2078_CR13","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0960-0760(00)00039-X","volume":"72","author":"F Arcuri","year":"2000","unstructured":"Arcuri F, Sestini S, Ricci C, Runci Y, Carducci A, Paulesu L, Cintorino M: Progestin regulation of 11beta-hydroxysteroid dehydrogenase expression in T-47D human breast cancer cells. J Steroid Biochem Mol Biol. 2000, 72: 239-247. 10.1016\/S0960-0760(00)00039-X.","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2078_CR14","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1021\/bc070135v","volume":"18","author":"G Cesarone","year":"2007","unstructured":"Cesarone G, Edupuganti OP, Chen CP, Wickstrom E: Insulin receptor substrate 1 knockdown in human MCF7 ER+ breast cancer cells by nuclease-resistant IRS1 siRNA conjugated to a disulfide-bridged D-peptide analogue of insulin-like growth factor 1. Bioconjug Chem. 2007, 18: 1831-1840. 10.1021\/bc070135v.","journal-title":"Bioconjug Chem"},{"key":"2078_CR15","doi-asserted-by":"publisher","first-page":"9338","DOI":"10.1128\/MCB.01032-06","volume":"26","author":"Z Ma","year":"2006","unstructured":"Ma Z, Gibson SL, Byrne MA, Zhang J, White MF, Shaw LM: Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis. Mol Cell Biol. 2006, 26: 9338-9351. 10.1128\/MCB.01032-06.","journal-title":"Mol Cell Biol"},{"key":"2078_CR16","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1002\/cncr.101970","volume":"94","author":"EE Calle","year":"2002","unstructured":"Calle EE, Rodriguez C, Jacobs EJ, Almon ML, Chao A, McCullough ML, Feigelson HS, Thun MJ: The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics. Cancer. 2002, 94: 2490-2501. 10.1002\/cncr.101970.","journal-title":"Cancer"},{"key":"2078_CR17","unstructured":"International HapMap Project. [http:\/\/www.hapmap.org]"},{"key":"2078_CR18","unstructured":"dbSNP. [http:\/\/www.ncbi.nlm.nih.gov\/SNP\/]"},{"key":"2078_CR19","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","volume":"21","author":"J Barrett","year":"2005","unstructured":"Barrett J, Fry B, Maller J, Daly M: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21: 263-265. 10.1093\/bioinformatics\/bth457.","journal-title":"Bioinformatics"},{"key":"2078_CR20","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1038\/ng1669","volume":"37","author":"PI de Bakker","year":"2005","unstructured":"de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D: Efficiency and power in genetic association studies. Nat Genet. 2005, 37: 1217-1223. 10.1038\/ng1669.","journal-title":"Nat Genet"},{"key":"2078_CR21","unstructured":"Autoprimer.com. [http:\/\/www.autoprimer.com]"},{"key":"2078_CR22","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1159\/000071807","volume":"55","author":"D Stram","year":"2003","unstructured":"Stram D, Haiman C, Hirschhorn J, Altshuler D, Kolonel L, Henderson B, Pike M: Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study. Hum Hered. 2003, 55: 27-36. 10.1159\/000071807.","journal-title":"Hum Hered"},{"key":"2078_CR23","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1158\/1055-9965.EPI-03-0301","volume":"13","author":"H Feigelson","year":"2004","unstructured":"Feigelson H, Jonas C, Teras L, Thun M, Calle E: Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2004, 13: 220-224. 10.1158\/1055-9965.EPI-03-0301.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2078_CR24","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1001\/jama.1997.03550170037029","volume":"278","author":"Z Huang","year":"1997","unstructured":"Huang Z, Hankinson S, Colditz G, Stampfer M, Hunter D, Manson J, Hennekens C, Rosner B, Speizer F, Willett W: Dual effects of weight and weight gain on breast cancer risk. JAMA. 1997, 278: 1407-1411. 10.1001\/jama.278.17.1407.","journal-title":"JAMA"},{"key":"2078_CR25","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1210\/jc.2005-2222","volume":"91","author":"A Gambineri","year":"2006","unstructured":"Gambineri A, Vicennati V, Genghini S, Tomassoni F, Pagotto U, Pasquali R, Walker BR: Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006, 91: 2295-2302. 10.1210\/jc.2005-2222.","journal-title":"J Clin Endocrinol Metab"},{"key":"2078_CR26","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/ng2075","volume":"39","author":"DJ Hunter","year":"2007","unstructured":"Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF, Hoover RN, Thomas G, Chanock SJ: A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007, 39: 870-874. 10.1038\/ng2075.","journal-title":"Nat Genet"},{"key":"2078_CR27","unstructured":"CGEMS: Cancer Genetic Markers of Susceptibility. [http:\/\/cgems.cancer.gov\/data]"},{"key":"2078_CR28","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1210\/jc.2004-1752","volume":"90","author":"CS Fox","year":"2005","unstructured":"Fox CS, Heard-Costa NL, Vasan RS, Murabito JM, D'Agostino RB, Atwood LD: Genomewide linkage analysis of weight change in the Framingham Heart Study. J Clin Endocrinol Metab. 2005, 90: 3197-3201. 10.1210\/jc.2004-1752.","journal-title":"J Clin Endocrinol Metab"},{"key":"2078_CR29","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1210\/jc.2006-1349","volume":"92","author":"P Smit","year":"2007","unstructured":"Smit P, Dekker MJ, de Jong FJ, Beld van den AW, Koper JW, Pols HA, Brinkmann AO, de Jong FH, Breteler MM, Lamberts SW: Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia. J Clin Endocrinol Metab. 2007, 92: 359-362. 10.1210\/jc.2006-1349.","journal-title":"J Clin Endocrinol Metab"},{"key":"2078_CR30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s00439-003-0935-3","volume":"113","author":"C Lautier","year":"2003","unstructured":"Lautier C, ElMkadem S, Renard E, Brun J, Gris J, Bringer J, Grigorescu F: Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation. Hum Genet. 2003, 113: 34-43.","journal-title":"Hum Genet"},{"key":"2078_CR31","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1158\/1055-9965.EPI-05-0149","volume":"14","author":"C Sweeney","year":"2005","unstructured":"Sweeney C, Murtaugh MA, Baumgartner KB, Byers T, Giuliano AR, Herrick JS, Wolff R, Caan BJ, Slattery ML: Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1802-1809. 10.1158\/1055-9965.EPI-05-0149.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2078_CR32","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1038\/oby.2007.269","volume":"15","author":"CL Saunders","year":"2007","unstructured":"Saunders CL, Chiodini BD, Sham P, Lewis CM, Abkevich V, Adeyemo AA, de Andrade M, Arya R, Berenson GS, Blangero J, Boehnke M, Borecki IB, Chagnon YC, Chen W, Comuzzie AG, Deng HW, Duggirala R, Feitosa MF, Froguel P, Hanson RL, Hebebrand J, Huezo-Dias P, Kissebah AH, Li W, Luke A, Martin LJ, Nash M, Ohman M, Palmer LJ, Peltonen L, et al: Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity (Silver Spring). 2007, 15: 2263-2275. 10.1038\/oby.2007.269.","journal-title":"Obesity (Silver Spring)"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr2114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/bcr2114\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr2114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:47:27Z","timestamp":1728384447000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/bcr2114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,8]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2008,8]]}},"alternative-id":["2078"],"URL":"https:\/\/doi.org\/10.1186\/bcr2114","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,8]]},"assertion":[{"value":"6 April 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2008","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2008","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2008","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R57"}}