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The objective of this systematic review was to assess epidemiologic evidence on etiologic factors for prostate cancer by tumor <jats:italic>TMPRSS2:ERG<\/jats:italic> fusion status in human populations. Of 3071 publications identified, 19 cohort or case\u2013control studies from six distinct study populations were included in this systematic review. Etiologic factors included germline genetic variants, circulating hormones, and dietary and lifestyle factors. Taller height, higher total and free testosterone levels, and fewer trinucleotide repeats in <jats:italic>AR<\/jats:italic> were possibly associated with higher risk of <jats:italic>TMPRSS2:ERG<\/jats:italic>\u2010positive prostate cancer. Excess body weight, greater vigorous physical activity, higher lycopene intake, and the use of calcium channel blockers were associated with lower risk of <jats:italic>TMPRSS2:ERG<\/jats:italic>\u2010positive prostate cancer. Diabetes and family history of prostate cancer were associated with both <jats:italic>TMPRSS2:ERG<\/jats:italic>\u2010positive and <jats:italic>TMPRSS2:ERG<\/jats:italic>\u2010negative prostate cancer. Prostate cancer germline variants had suggestive differential associations with <jats:italic>TMPRSS2:ERG<\/jats:italic>\u2010positive or <jats:italic>TMPRSS2:ERG<\/jats:italic>\u2010negative prostate cancer. However, results were based on few distinct study populations and generally had low precision, underscoring the need for replication. In conclusion, prostate cancer with <jats:italic>TMPRSS2:ERG<\/jats:italic> fusion is an etiologically distinct subtype that may be, in part, preventable by addressing modifiable and hormonally acting etiologic factors that align with the established mechanistic role of <jats:italic>TMPRSS2:ERG<\/jats:italic> in androgen, insulin, antioxidant, and growth factor pathways.<\/jats:p>","DOI":"10.1002\/ijc.35279","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T06:04:52Z","timestamp":1733983492000},"page":"1898-1908","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Etiology of prostate cancer with the <i>TMPRSS2:ERG<\/i> fusion: A systematic review of risk factors"],"prefix":"10.1002","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-2955","authenticated-orcid":false,"given":"Colleen B.","family":"McGrath","sequence":"first","affiliation":[{"name":"Department of Epidemiology Harvard T. 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