{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:16:14Z","timestamp":1791029774244,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2007,4,11]],"date-time":"2007-04-11T00:00:00Z","timestamp":1176249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2007,4,11]],"date-time":"2007-04-11T00:00:00Z","timestamp":1176249600000},"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>Certain rare, familial mutations in the <jats:italic>ATM<\/jats:italic>, <jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>CHEK2<\/jats:italic> or <jats:italic>TP53<\/jats:italic> genes increase susceptibility to breast cancer but it has not, until now, been clear whether common polymorphic variants in the same genes also increase risk.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We have attempted a comprehensive, single nucleotide polymorphism (SNP)- and haplotype-tagging association study on each of these five genes in up to 4,474 breast cancer cases from the British, East Anglian SEARCH study and 4,560 controls from the EPIC-Norfolk study, using a two-stage study design. Nine tag SNPs were genotyped in <jats:italic>ATM<\/jats:italic>, together with five in <jats:italic>BRCA1<\/jats:italic>, sixteen in <jats:italic>BRCA2<\/jats:italic>, ten in <jats:italic>CHEK2<\/jats:italic> and five in <jats:italic>TP53<\/jats:italic>, with the aim of tagging all other known, common variants. SNPs generating the common amino acid substitutions were specifically forced into the tagging set for each gene.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>No significant breast cancer associations were detected with any individual or combination of tag SNPs.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>It is unlikely that there are any other common variants in these genes conferring measurably increased risks of breast cancer in our study population.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr1669","type":"journal-article","created":{"date-parts":[[2007,4,30]],"date-time":"2007-04-30T15:52:13Z","timestamp":1177948333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk"],"prefix":"10.1186","volume":"9","author":[{"given":"Caroline","family":"Baynes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine S","family":"Healey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A","family":"Pooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Scollen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N","family":"Luben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul DP","family":"Pharoah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F","family":"Easton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce AJ","family":"Ponder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M","family":"Dunning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the SEARCH breast cancer study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,4,11]]},"reference":[{"key":"1634_CR1","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1086\/421251","volume":"74","author":"CHEK2 Breast Cancer Case-Control Consortium","year":"2004","unstructured":"CHEK2 Breast Cancer Case-Control Consortium: CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004, 74: 1175-1182. 10.1086\/421251.","journal-title":"Am J Hum Genet"},{"key":"1634_CR2","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1054\/bjoc.2000.1407","volume":"83","author":"Anglian Breast Cancer Study Group","year":"2000","unstructured":"Anglian Breast Cancer Study Group: Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000, 83: 1301-1308. 10.1054\/bjoc.2000.1407.","journal-title":"Br J Cancer"},{"key":"1634_CR3","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1093\/jnci\/91.11.943","volume":"91","author":"J Peto","year":"1999","unstructured":"Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR: Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst. 1999, 91: 943-949. 10.1093\/jnci\/91.11.943.","journal-title":"J Natl Cancer Inst"},{"key":"1634_CR4","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/sj.bjc.6600008","volume":"86","author":"AC Antoniou","year":"2002","unstructured":"Antoniou AC, Pharoah PD, McMullan G, Day NE, Stratton MR, Peto J, Ponder BJ, Easton DF: A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes. Br J Cancer. 2002, 86: 76-83. 10.1038\/sj.bjc.6600008.","journal-title":"Br J Cancer"},{"key":"1634_CR5","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/ng853","volume":"31","author":"PD Pharoah","year":"2002","unstructured":"Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA: Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002, 31: 33-36. 10.1038\/ng853.","journal-title":"Nat Genet"},{"key":"1634_CR6","doi-asserted-by":"publisher","first-page":"3904","DOI":"10.1167\/iovs.04-0628","volume":"45","author":"Y Tamimi","year":"2004","unstructured":"Tamimi Y, Lines M, Coca-Prados M, Walter MA: Identification of target genes regulated by FOXC1 using nickel agarose-based chromatin enrichment. Invest Ophthalmol Vis Sci. 2004, 45: 3904-3913. 10.1167\/iovs.04-0628.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1634_CR7","doi-asserted-by":"publisher","first-page":"R171","DOI":"10.1186\/bcr973","volume":"7","author":"DG Cox","year":"2005","unstructured":"Cox DG, Kraft P, Hankinson SE, Hunter DJ: Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer. Breast Cancer Res. 2005, 7: R171-R175. 10.1186\/bcr973.","journal-title":"Breast Cancer Res"},{"key":"1634_CR8","doi-asserted-by":"publisher","first-page":"7516","DOI":"10.1158\/0008-5472.CAN-05-0132","volume":"65","author":"ML Freedman","year":"2005","unstructured":"Freedman ML, Penney KL, Stram DO, Riley S, McKean-Cowdin R, Le Marchand L, Altshuler D, Haiman CA: A haplotype-based case-control study of BRCA1 and sporadic breast cancer risk. Cancer Res. 2005, 65: 7516-7522. 10.1158\/0008-5472.CAN-05-0132.","journal-title":"Cancer Res"},{"key":"1634_CR9","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1093\/hmg\/ddh270","volume":"13","author":"ML Freedman","year":"2004","unstructured":"Freedman ML, Penney KL, Stram DO, Le Marchand L, Hirschhorn JN, Kolonel LN, Altshuler D, Henderson BE, Haiman CA: Common variation in BRCA2 and breast cancer risk: a haplotype-based analysis in the Multiethnic Cohort. Hum Mol Genet. 2004, 13: 2431-2441. 10.1093\/hmg\/ddh270.","journal-title":"Hum Mol Genet"},{"key":"1634_CR10","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1158\/1055-9965.EPI-04-0848","volume":"14","author":"DG Cox","year":"2005","unstructured":"Cox DG, Hankinson SE, Hunter DJ: No association between BRCA2 N372H and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1353-1354. 10.1158\/1055-9965.EPI-04-0848.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1634_CR11","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/81691","volume":"26","author":"CS Healey","year":"2000","unstructured":"Healey CS, Dunning AM, Teare MD, Chase D, Parker L, Burn J, Chang-Claude J, Mannermaa A, Kataja V, Huntsman DG, et al: A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability. Nat Genet. 2000, 26: 362-364. 10.1038\/81691.","journal-title":"Nat Genet"},{"key":"1634_CR12","first-page":"413","volume":"11","author":"AB Spurdle","year":"2002","unstructured":"Spurdle AB, Hopper JL, Chen X, Dite GS, Cui J, McCredie MR, Giles GG, Ellis-Steinborner S, Venter DJ, Newman B, et al: The BRCA2 372 HH genotype is associated with risk of breast cancer in Australian women under age 60 years. Cancer Epidemiol Biomarkers Prev. 2002, 11: 413-416.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1634_CR13","doi-asserted-by":"publisher","first-page":"e168","DOI":"10.1371\/journal.pmed.0030168","volume":"3","author":"K Einarsdottir","year":"2006","unstructured":"Einarsdottir K, Humphreys K, Bonnard C, Palmgren J, Iles MM, Sjolander A, Li Y, Chia KS, Liu ET, Hall P, et al: Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk. PLoS Med. 2006, 3: e168-10.1371\/journal.pmed.0030168.","journal-title":"PLoS Med"},{"key":"1634_CR14","first-page":"1513","volume":"11","author":"EL Goode","year":"2002","unstructured":"Goode EL, Ulrich CM, Potter JD: Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1513-1530.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1634_CR15","unstructured":"NIEHS Environmental Genome Project. [http:\/\/egp.gs.washington.edu\/]"},{"key":"1634_CR16","unstructured":"HAPMAP Project. [http:\/\/www.HAPMAP.org]"},{"key":"1634_CR17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1159\/000071807","volume":"55","author":"DO Stram","year":"2003","unstructured":"Stram DO, Haiman CA, Hirschhorn JN, Altshuler D, Kolonel LN, Henderson BE, Pike MC: 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":"1634_CR18","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1093\/jnci\/djj374","volume":"98","author":"Breast Cancer Association Consortium","year":"2006","unstructured":"Breast Cancer Association Consortium: Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst. 2006, 98: 1382-1396.","journal-title":"J Natl Cancer Inst"},{"key":"1634_CR19","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1093\/hmg\/6.2.285","volume":"6","author":"AM Dunning","year":"1997","unstructured":"Dunning AM, Chiano M, Smith NR, Dearden J, Gore M, Oakes S, Wilson C, Stratton M, Peto J, Easton D, et al: Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum Mol Genet. 1997, 6: 285-289. 10.1093\/hmg\/6.2.285.","journal-title":"Hum Mol Genet"},{"key":"1634_CR20","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1086\/321296","volume":"69","author":"YR Thorstenson","year":"2001","unstructured":"Thorstenson YR, Shen P, Tusher VG, Wayne TL, Davis RW, Chu G, Oefner PJ: Global analysis of ATM polymorphism reveals significant functional constraint. Am J Hum Genet. 2001, 69: 396-412. 10.1086\/321296.","journal-title":"Am J Hum Genet"},{"key":"1634_CR21","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1136\/jmg.2003.017293","volume":"41","author":"MD Teare","year":"2004","unstructured":"Teare MD, Cox A, Shorto J, Anderson C, Bishop DT, Cannings C: Heterozygote excess is repeatedly observed in females at the BRCA2 locus N372H. J Med Genet. 2004, 41: 523-528. 10.1136\/jmg.2003.017293.","journal-title":"J Med Genet"},{"key":"1634_CR22","unstructured":"BIC Database. [http:\/\/research.nhgri.nih.gov\/bic\/]"},{"key":"1634_CR23","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/ng1837","volume":"38","author":"A Renwick","year":"2006","unstructured":"Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, et al: ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet. 2006, 38: 873-875. 10.1038\/ng1837.","journal-title":"Nat Genet"},{"key":"1634_CR24","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1002\/humu.20323","volume":"27","author":"DL Stredrick","year":"2006","unstructured":"Stredrick DL, Garcia-Closas M, Pineda MA, Bhatti P, Alexander BH, Doody MM, Lissowska J, Peplonska B, Brinton LA, Chanock SJ, et al: The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer. Hum Mutat. 2006, 27: 538-544. 10.1002\/humu.20323.","journal-title":"Hum Mutat"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr1669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/bcr1669\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr1669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:52:26Z","timestamp":1728384746000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/bcr1669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,11]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2007,12]]}},"alternative-id":["1634"],"URL":"https:\/\/doi.org\/10.1186\/bcr1669","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,11]]},"assertion":[{"value":"29 January 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2007","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2007","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2007","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R27"}}