{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:03:12Z","timestamp":1791028992772,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,3,8]],"date-time":"2005-03-08T00:00:00Z","timestamp":1110240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2005,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ATM kinase has an essential role in maintaining genomic integrity. Loss of both <jats:italic>ATM<\/jats:italic> alleles results in ataxia\u2010telangiectasia (A\u2010T), a rare autosomal recessive neuroimmunologic disorder associated with cancer susceptibility. Individuals heterozygous for germline <jats:italic>ATM<\/jats:italic> mutations have been reported to have an increased risk for malignancy, in particular, female breast cancer. In the current study, a full mutation analysis of the <jats:italic>ATM<\/jats:italic> gene was carried out in patients from 121 breast or breast\u2010ovarian cancer families. We discovered that the combination of 5557G\u2192A in cis position with IVS38\u20108 T\u2192C was associated with bilateral breast cancer (OR = 10.2; 95% CI = 3.1\u201333.8; <jats:italic>p<\/jats:italic> = 0.001). As the 5557G\u2192A change has been reported to affect an exonic splicing enhancer, we hypothesized that the observed composite allele could have some effect on the correct splicing of exon 39. However, no aberrant transcripts were detected, but <jats:italic>ATM<\/jats:italic> expression levels of lymphoblast cell lines from heterozygous carriers of this combination allele were lower than from noncarriers (<jats:italic>p<\/jats:italic> = 0.09). Lowered gene expression levels may have direct influence on the activities in DNA damage recognition and response pathways, as well as other genome integrity maintenance functions. Based on the results, we propose a cancer risk\u2010modifying effect for the <jats:italic>ATM<\/jats:italic> 5557G\u2192A, IVS38\u20108T\u2192C composite allele. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20996","type":"journal-article","created":{"date-parts":[[2005,3,8]],"date-time":"2005-03-08T18:47:35Z","timestamp":1110307655000},"page":"69-72","source":"Crossref","is-referenced-by-count":36,"title":["Association of common <i>ATM<\/i> polymorphism with bilateral breast cancer"],"prefix":"10.1002","volume":"116","author":[{"given":"Katri","family":"Heikkinen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Rapakko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna\u2010Maria","family":"Karppinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannele","family":"Erkko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pentti","family":"Nieminen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Winqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,8]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1011"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.07.042"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.177"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198705213162101"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112263252602"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/09553009414552011"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOMG.0000048772.92326.a1"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200009)16:3<232::AID-HUMU6>3.0.CO;2-L"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.3.192"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/301880"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1681"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10059"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/302418"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.2.7312"},{"key":"e_1_2_5_16_2","first-page":"7608","article-title":"Spectrum of ATM gene mutations in a hospital\u2010based series of unselected breast cancer patients","volume":"61","author":"D\u00f6rk T","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_17_2","first-page":"3325","article-title":"Contributions of ATM mutations to familial breast and ovarian cancer","volume":"63","author":"Thorstenson YR","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20001215)88:6<928::AID-IJC14>3.0.CO;2-P"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-1269"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010801)92:3<479::AID-CNCR1346>3.0.CO;2-G"},{"key":"e_1_2_5_21_2","first-page":"8717","article-title":"ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity","volume":"63","author":"Ang\u00e8le S","year":"2003","journal-title":"Cancer 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