{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:23Z","timestamp":1787828303299,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA235553"],"award-info":[{"award-number":["R01 CA235553"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Many risk factors have been identified for breast cancer. The potential causality for some of them remains uncertain, and few studies have comprehensively investigated these associations by molecular subtypes. We performed a two\u2010sample Mendelian randomization (MR) study to evaluate potential causal associations of 23 known and suspected risk factors and biomarkers with breast cancer risk overall and by molecular subtypes using data from the Breast Cancer Association Consortium. The inverse\u2010variance weighted method was used to estimate odds ratios (OR) and 95% confidence interval (CI) for association of each trait with breast cancer risk. Significant associations with breast cancer risk were found for 15 traits, including age at menarche, age at menopause, body mass index, waist\u2010to\u2010hip ratio, height, physical activity, cigarette smoking, sleep duration, and morning\u2010preference chronotype, and six blood biomarkers (estrogens, insulin\u2010like growth factor\u20101, sex hormone\u2010binding globulin [SHBG], telomere length, HDL\u2010cholesterol and fasting insulin). Noticeably, an increased circulating SHBG was associated with a reduced risk of estrogen receptor (ER)\u2010positive cancer (OR\u00a0=\u00a00.83, 95% CI: 0.73\u20100.94), but an elevated risk of ER\u2010negative (OR\u00a0=\u00a01.12, 95% CI: 0.93\u20101.36) and triple negative cancer (OR\u00a0=\u00a01.19, 95% CI: 0.92\u20101.54) (<jats:italic>P<\/jats:italic><jats:sub>heterogeneity<\/jats:sub>\u00a0=\u00a00.01). Fasting insulin was most strongly associated with an increased risk of HER2\u2010negative cancer (OR\u00a0=\u00a01.94, 95% CI: 1.18\u20103.20), but a reduced risk of HER2\u2010enriched cancer (OR\u00a0=\u00a00.46, 95% CI: 0.26\u20100.81) (<jats:italic>P<\/jats:italic><jats:sub>heterogeneity<\/jats:sub>\u00a0=\u00a00.006). Results from sensitivity analyses using MR\u2010Egger and MR\u2010PRESSO were generally consistent. Our study provides strong evidence supporting potential causal associations of several risk factors for breast cancer and suggests potential heterogeneous associations of SHBG and fasting insulin levels with subtypes of breast cancer.<\/jats:p>","DOI":"10.1002\/ijc.34026","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T10:51:11Z","timestamp":1649674271000},"page":"372-380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes"],"prefix":"10.1002","volume":"151","author":[{"given":"Fa","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Epidemiology and Health Statistics, School of Public Health Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqing","family":"Wen","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirong","family":"Long","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Shu","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohua","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-8314","authenticated-orcid":false,"given":"Xiao\u2010Ou","family":"Shu","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-070X","authenticated-orcid":false,"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt\u2010Ingram Cancer Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"International Agency for Research on Cancer.Cancer Tomorrow.http:\/\/gco.iarc.fr\/tomorrow\/home. Accessed September 22 2021."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70425-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0582"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv156"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw103"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70095-4"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3412"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv219"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002105"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3841"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy201"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14389-8"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2020.06.001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.01.066"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz242"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291719002678"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6303"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-13-53"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy271"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy327"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19806"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07743-4"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0309-3"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0307-5"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0333-3"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08259-7"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2385"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04951-w"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003062"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.02.006"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00757"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002805"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0609-2"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24284"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz107"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l2327"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-20-1218"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.5945"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djr030"},{"issue":"20","key":"e_1_2_11_46_1","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.1158\/0008-5472.CAN-18-0502","article-title":"Pooled analysis of nine cohorts reveals breast cancer risk factors by tumor molecular subtype","volume":"78","author":"Gaudet MM","year":"2018","journal-title":"Cancer Res"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.4158"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-016-0799-9"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31258"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-015-0291-7"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn415"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.34026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.34026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.34026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T23:11:04Z","timestamp":1692832264000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.34026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/ijc.34026"],"URL":"https:\/\/doi.org\/10.1002\/ijc.34026","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,26]]},"assertion":[{"value":"2021-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}