{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T04:13:39Z","timestamp":1728965619043},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2014,12,11]],"date-time":"2014-12-11T00:00:00Z","timestamp":1418256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,12,11]],"date-time":"2014-12-11T00:00:00Z","timestamp":1418256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"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>Mammographic density (MD) is a strong biomarker of breast cancer risk. MD increases after women start estrogen plus progestin therapy (EPT) and decreases after women quit EPT. A large interindividual variation in EPT-associated MD change has been observed, but few studies have investigated genetic predictors of the EPT-associated MD change. Here, we evaluate the association between polymorphisms in hormone metabolism pathway genes and MD changes when women quit EPT.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We collected mammograms before and after women quit EPT and genotyped 405 tagging single nucleotide polymorphisms (SNPs) in 30 hormone metabolism pathway genes in 284 non-Hispanic white participants of the California Teachers Study (CTS). Participants were ages 49 to 71\u00a0years at time of mammography taken after quitting EPT. We assessed percent MD using a computer-assisted method. MD change was calculated by subtracting MD of an \u2018off-EPT\u2019 mammogram from MD of an \u2018on-EPT\u2019 (that is baseline) mammogram. Linear regression analysis was used to investigate the SNP-MD change association, adjusting for the baseline \u2018on-EPT\u2019 MD, age and BMI at time of baseline mammogram, and time interval and BMI change between the two mammograms. An overall pathway and gene-level summary was obtained using the adaptive rank truncated product (ARTP) test. We calculated \u2018<jats:italic>P<\/jats:italic> values adjusted for correlated tests (<jats:italic>P<\/jats:italic><jats:sub>ACT<\/jats:sub>)\u2019 to account for multiple testing within a gene.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>The strongest associations were observed for rs7489119 in <jats:italic>SLCO1B1<\/jats:italic>, and rs5933863 in <jats:italic>ARSC<\/jats:italic>. SLCO1B1 and ARSC are involved in excretion and activation of estrogen metabolites of EPT, respectively. MD change after quitting was 4.2% smaller per minor allele of rs7489119 (<jats:italic>P<\/jats:italic>\u2009=\u20090.0008; <jats:italic>P<\/jats:italic><jats:sub>ACT<\/jats:sub>\u2009=\u20090.018) and 1.9% larger per minor allele of rs5933863 (<jats:italic>P<\/jats:italic>\u2009=\u20090.013; <jats:italic>P<\/jats:italic><jats:sub>ACT<\/jats:sub>\u2009=\u20090.025). These individual SNP associations did not reach statistical significance when we further used Bonferroni correction to consider the number of tested genes. The pathway level summary ARTP <jats:italic>P<\/jats:italic> value was not statistically significant.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Data from this longitudinal study of EPT quitters suggest that genetic variation in two hormone metabolism pathway genes, <jats:italic>SLCO1B1<\/jats:italic> and <jats:italic>ARSC<\/jats:italic>, may be associated with change in MD after women stop using EPT. Larger longitudinal studies are needed to confirm our findings.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/s13058-014-0477-8","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T19:21:35Z","timestamp":1418239295000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hormone metabolism pathway genes and mammographic density change after quitting estrogen and progestin combined hormone therapy in the California Teachers Study"],"prefix":"10.1186","volume":"16","author":[{"given":"Eunjung","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianning","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chen","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Pablo","family":"Lewinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrick R","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Van Den Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna H","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giske","family":"Ursin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,12,11]]},"reference":[{"key":"477_CR1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1158\/1055-9965.EPI-06-0034","volume":"15","author":"VA McCormack","year":"2006","unstructured":"McCormack VA, dos Santos SI: Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. 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