{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:25:00Z","timestamp":1773289500638,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T00:00:00Z","timestamp":1110499200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T00:00:00Z","timestamp":1110499200000},"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>Background<\/jats:title>\n                        <jats:p>Overexpression of the <jats:italic>HER2<\/jats:italic> proto-oncogene in human cancer cells has been associated with a poor prognosis, and survival improves with therapy targeting the <jats:italic>HER2<\/jats:italic> gene. Animal studies and protein modeling suggest that the Ile655Val polymorphism located in the transmembrane domain of the HER2 protein might influence breast cancer development by altering the efficiency of homodimerization.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>To investigate this genetic polymorphism, incident cases of invasive breast cancer (<jats:italic>N<\/jats:italic> = 1,094) and population controls of a similar age (<jats:italic>N<\/jats:italic> = 976) were interviewed during 2001 to 2003 regarding their risk factors for breast cancer. By using DNA collected from buccal samples mailed by the participants, the <jats:italic>HER2<\/jats:italic> Ile655Val polymorphism was evaluated with the Applied Biosystems allelic discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression adjusted for numerous breast cancer risk factors. Analysis was restricted to women with self-reported European descent.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Prevalence of the Val\/Val genotype was 5.6% in cases and 7.1% in controls. In comparison with the Ile\/Ile genotype, the Ile\/Val genotype was not significantly associated with breast cancer risk (OR 0.97, 95% CI 0.79 to 1.18), whereas the Val\/Val genotype was associated with a reduced risk (OR 0.63, 95% CI 0.42 to 0.92). This inverse association seemed strongest in older women (OR 0.51, 95% CI 0.29 to 0.89 for women aged more than 55 years), women without a family history of breast cancer (OR 0.54, 95% CI 0.35 to 0.84), postmenopausal women with greater body mass index (OR 0.43, 95% CI 0.20 to 0.91 for a body mass index of 25.3 kg\/m<jats:sup>2<\/jats:sup> or more), and cases diagnosed with non-localized breast cancer (OR 0.49, 95% CI 0.26 to 0.90).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Although results from our population-based case-control study show an inverse association between the <jats:italic>HER2<\/jats:italic> Ile655Val polymorphism and risk of invasive breast cancer, most other studies of this single-nucleotide polymorphism suggest an overall null association. Any further study of this polymorphism should involve sample populations with complete risk factor information and sufficient power to evaluate gene-environment interactions between the <jats:italic>HER2<\/jats:italic> polymorphism and factors such as age and family history of breast cancer.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr1004","type":"journal-article","created":{"date-parts":[[2005,3,12]],"date-time":"2005-03-12T07:15:51Z","timestamp":1110611751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer"],"prefix":"10.1186","volume":"7","author":[{"given":"Stephanie E","family":"Nelson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael N","family":"Gould","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M","family":"Hampton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Trentham-Dietz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,3,11]]},"reference":[{"issue":"Suppl 1","key":"1002_CR1","doi-asserted-by":"publisher","first-page":"S23","DOI":"10.1093\/annonc\/12.suppl_1.S23","volume":"12","author":"T Cooke","year":"2001","unstructured":"Cooke T, Reeves J, Lanigan A, Stanton P: HER2 as a prognostic and predictive marker for breast cancer. 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