{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:45:39Z","timestamp":1776087939600,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: Homozygous or compound heterozygous mutations in the ATM gene are the principal cause of ataxia telangiectasia (A-T). Several studies have suggested that heterozygous carriers of ATM mutations are at increased risk of breast cancer and perhaps of other cancers, but the precise risk is uncertain. Methods: Cancer incidence and mortality information for 1160 relatives of 169 UK A-T patients (including 247 obligate carriers) was obtained through the National Health Service Central Registry. Relative risks (RRs) of cancer in carriers, allowing for genotype uncertainty, were estimated with a maximum-likelihood approach that used the EM algorithm. Maximum-likelihood estimates of cancer risks associated with three groups of mutations were calculated using the pedigree analysis program MENDEL. All statistical tests were two-sided. Results: The overall relative risk of breast cancer in carriers was 2.23 (95% confidence interval [CI] = 1.16 to 4.28) compared with the general population but was 4.94 (95% CI = 1.90 to 12.9) in those younger than age 50 years. The relative risk for all cancers other than breast cancer was 2.05 (95% CI = 1.09 to 3.84) in female carriers and 1.23 (95% CI = 0.76 to 2.00) in male carriers. Breast cancer was the only site for which a clear risk increase was seen, although there was some evidence of excess risks of colorectal cancer (RR = 2.54, 95% CI = 1.06 to 6.09) and stomach cancer (RR = 3.39, 95% CI = 0.86 to 13.4). Carriers of mutations predicted to encode a full-length ATM protein had cancer risks similar to those of people carrying truncating mutations. Conclusion: These results confirm a moderate risk of breast cancer in A-T heterozygotes and give some evidence of an excess risk of other cancers but provide no support for large mutation-specific differences in risk.<\/jats:p>","DOI":"10.1093\/jnci\/dji141","type":"journal-article","created":{"date-parts":[[2005,5,31]],"date-time":"2005-05-31T23:05:35Z","timestamp":1117580735000},"page":"813-822","source":"Crossref","is-referenced-by-count":436,"title":["Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers"],"prefix":"10.1093","volume":"97","author":[{"given":"Deborah","family":"Thompson","sequence":"first","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Silvia","family":"Duedal","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Jennifer","family":"Kirner","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Lesley","family":"McGuffog","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"James","family":"Last","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Anne","family":"Reiman","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Philip","family":"Byrd","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Malcolm","family":"Taylor","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]},{"given":"Douglas F.","family":"Easton","sequence":"additional","affiliation":[{"name":"Affiliations of authors: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK (DT, SD, JK, LM, DFE); Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK (JL, AR, PB, MT)"}]}],"member":"286","published-online":{"date-parts":[[2005,6,1]]},"reference":[{"key":"2021060418545974400_BIB1","unstructured":"Morrell D, Cromartie E, Swift M. 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Absence of mutations in the ATM gene in forty-seven cases of sporadic breast cancer. \n            Br J Cancer\n\u00a01999\n            ;\n            80\n            :\n            1979\n            \u201381.","DOI":"10.1038\/sj.bjc.6690630"},{"key":"2021060418545974400_BIB14","doi-asserted-by":"crossref","unstructured":"Buchholz TA, Weil MM, Ashorn CL, Strom EA, Sigurdson A, Bondy M, et al. A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls. \n            Cancer\n\u00a02004\n            ;\n            100\n            :\n            1345\n            \u201351.","DOI":"10.1002\/cncr.20133"},{"key":"2021060418545974400_BIB15","doi-asserted-by":"crossref","unstructured":"Izatt L, Greenman J, Hodgson S, Ellis D, Watts S, Scott G, et al. Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer. \n            Genes Chromosomes Cancer\n\u00a01999\n            ;\n            26\n            :\n            286\n            \u201394.","DOI":"10.1002\/(SICI)1098-2264(199912)26:4<286::AID-GCC2>3.0.CO;2-X"},{"key":"2021060418545974400_BIB16","doi-asserted-by":"crossref","unstructured":"Shafman TD, Levitz S, Nixon AJ, Gibans LA, Nichols KE, Bell DW, et al. Prevalence of germline truncating mutations in ATM in women with a second breast cancer after radiation therapy for a contralateral tumor. \n            Genes Chromosomes Cancer\n\u00a02000\n            ;\n            27\n            :\n            124\n            \u20139.","DOI":"10.1002\/(SICI)1098-2264(200002)27:2<124::AID-GCC2>3.0.CO;2-M"},{"key":"2021060418545974400_BIB17","unstructured":"Thorstenson YR, Roxas A, Kroiss R, Jenkins MA, Yu KM, Bachrich T, et al. Contributions of ATM mutations to familial breast and ovarian cancer. \n            Cancer Res\n\u00a02003\n            ;\n            63\n            :\n            3325\n            \u201333."},{"key":"2021060418545974400_BIB18","unstructured":"Chen J, Birkholtz GG, Lindblom P, Rubio C, Lindblom A. The role of ataxia-telangiectasia heterozygotes in familial breast cancer. \n            Cancer Res\n\u00a01998\n            ;\n            58\n            :\n            1376\n            \u20139."},{"key":"2021060418545974400_BIB19","doi-asserted-by":"crossref","unstructured":"Chenevix-Trench G, Spurdle AB, Gatei M, Kelly H, Marsh A, Chen X, et al. Dominant negative ATM mutations in breast cancer families. \n            J Natl Cancer Inst\n\u00a02002\n            ;\n            94\n            :\n            205\n            \u201315.","DOI":"10.1093\/jnci\/94.3.205"},{"key":"2021060418545974400_BIB20","unstructured":"Dork T, Bendix R, Bremer M, Rades D, Klopper K, Nicke M, et al. Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients. \n            Cancer Res\n\u00a02001\n            ;\n            61\n            :\n            7608\n            \u201315."},{"key":"2021060418545974400_BIB21","doi-asserted-by":"crossref","unstructured":"Gatti RA, Tward A, Concannon P. Cancer risk in ATM heterozygotes: a model of phenotypic and mechanistic differences between missense and truncating mutations. \n            Mol Genet Metab\n\u00a01999\n            ;\n            68\n            :\n            419\n            \u201323.","DOI":"10.1006\/mgme.1999.2942"},{"key":"2021060418545974400_BIB22","doi-asserted-by":"crossref","unstructured":"Stankovic T, Kidd AM, Sutcliffe A, McGuire GM, Robinson P, Weber P, et al. ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. \n            Am J Hum Genet\n\u00a01998\n            ;\n            62\n            :\n            334\n            \u201345.","DOI":"10.1086\/301706"},{"key":"2021060418545974400_BIB23","doi-asserted-by":"crossref","unstructured":"Bernstein JL, Bernstein L, Thompson WD, Lynch CF, Malone KE, Teitelbaum SL, et al. ATM variants 7271T&gt;G and IVS10\u20136T&gt;G among women with unilateral and bilateral breast cancer. \n            Br J Cancer\n\u00a02003\n            ;\n            89\n            :\n            1513\n            \u20136.","DOI":"10.1038\/sj.bjc.6601289"},{"key":"2021060418545974400_BIB24","doi-asserted-by":"crossref","unstructured":"Spurdle AB, Hopper JL, Chen X, McCredie MR, Giles GG, Newman B, et al. No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer. \n            Breast Cancer Res\n\u00a02002\n            ;\n            4\n            :\n            R15\n            .","DOI":"10.1186\/bcr534"},{"key":"2021060418545974400_BIB25","doi-asserted-by":"crossref","unstructured":"Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. \n            Cell\n\u00a01999\n            ;\n            99\n            :\n            577\n            \u201387.","DOI":"10.1016\/S0092-8674(00)81547-0"},{"key":"2021060418545974400_BIB26","unstructured":"Muir C, Waterhouse J, Mack T, Powell J, et al. Cancer incidence in five continents. Vol V. 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