{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:10:39Z","timestamp":1762542639480,"version":"3.37.3"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T00:00:00Z","timestamp":1489968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01 CA108964","P30 CA006973","P30 CA054174","T32 CA009314","U10 CA37429","UM1 CA182883"],"award-info":[{"award-number":["P01 CA108964","P30 CA006973","P30 CA054174","T32 CA009314","U10 CA37429","UM1 CA182883"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower\u2010 and higher\u2010grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls.<\/jats:p><jats:p>Methods A total of 16 candidate SNPs in <jats:italic>IL1\u03b2<\/jats:italic>, <jats:italic>IL2<\/jats:italic>, <jats:italic>IL4<\/jats:italic>, <jats:italic>IL6<\/jats:italic>, <jats:italic>IL8<\/jats:italic>, <jats:italic>IL10<\/jats:italic>, <jats:italic>IL12(p40)<\/jats:italic>, <jats:italic>IFNG<\/jats:italic>, <jats:italic>MSR1<\/jats:italic>, <jats:italic>RNASEL<\/jats:italic>, <jats:italic>TLR4<\/jats:italic>, and <jats:italic>TNFA<\/jats:italic> and 7 tagSNPs in <jats:italic>IL10<\/jats:italic> were genotyped in 625 white prostate cancer cases, and 532 white controls negative for cancer on an end\u2010of\u2010study biopsy nested in the PCPT finasteride arm. We used logistic regression to estimate log\u2010additive odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Minor alleles of rs2243250 (T) in <jats:italic>IL4<\/jats:italic> (OR\u2009=\u20091.46, 95% CI 1.03\u20102.08, P\u2010trend\u2009=\u20090.03), rs1800896 (G) in <jats:italic>IL10<\/jats:italic> (OR\u2009=\u20090.77, 95% CI 0.61\u20100.96, P\u2010trend\u2009=\u20090.02), rs2430561 (A) in <jats:italic>IFNG<\/jats:italic> (OR\u2009=\u20091.33, 95% CI 1.02\u20101.74; P\u2010trend\u2009=\u20090.04), rs3747531 (C) in <jats:italic>MSR1<\/jats:italic> (OR\u2009=\u20090.55, 95% CI 0.32\u20100.95; P\u2010trend\u2009=\u20090.03), and possibly rs4073 (A) in <jats:italic>IL8<\/jats:italic> (OR\u2009=\u20090.81, 95% CI 0.64\u20101.01, P\u2010trend\u2009=\u20090.06) were associated with higher\u2010 (Gleason 7\u201010; <jats:italic>N<\/jats:italic>\u2009=\u2009222), but not lower\u2010 (Gleason 2\u20106; <jats:italic>N<\/jats:italic>\u2009=\u2009380) grade prostate cancer. In men with low PSA (&lt;2\u2009ng\/mL), these higher\u2010grade disease associations were attenuated and\/or no longer significant, whereas associations with higher\u2010grade disease were apparent for minor alleles of rs1800795 (C: OR\u2009=\u20090.70, 95% CI 0.51\u20100.94, P\u2010trend\u2009=\u20090.02) and rs1800797 (A: OR\u2009=\u20090.72, 95% CI 0.53\u20100.98, P\u2010trend\u2009=\u20090.04) in <jats:italic>IL6<\/jats:italic>. While some <jats:italic>IL10<\/jats:italic> tagSNPs were associated with lower\u2010 and higher\u2010grade prostate cancer, distributions of <jats:italic>IL10<\/jats:italic> haplotypes did not differ, except possibly between higher\u2010grade cases and controls among those with low PSA (<jats:italic>P<\/jats:italic>\u2009=\u20090.07). We did not observe an association between the studied SNPs and intraprostatic inflammation in the controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>In the PCPT finasteride arm, variation in genes involved in the immune response, including possibly <jats:italic>IL8<\/jats:italic> and <jats:italic>IL10<\/jats:italic> as in the placebo arm, may be associated with prostate cancer, especially higher\u2010grade disease, but not with intraprostatic inflammation. We cannot rule out PSA\u2010associated detection bias or chance due to multiple testing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23346","type":"journal-article","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T05:32:39Z","timestamp":1489987959000},"page":"908-919","source":"Crossref","is-referenced-by-count":19,"title":["Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride arm in the Prostate Cancer Prevention Trial"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-4347","authenticated-orcid":false,"given":"Danyelle A.","family":"Winchester","sequence":"first","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathee","family":"Till","sequence":"additional","affiliation":[{"name":"SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phyllis J.","family":"Goodman","sequence":"additional","affiliation":[{"name":"SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine M.","family":"Tangen","sequence":"additional","affiliation":[{"name":"SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina M.","family":"Santella","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Mailman School of Public Health Columbia University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa L.","family":"Johnson\u2010Pais","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Health Science Center at San Antonio San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin J.","family":"Leach","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Health Science Center at San Antonio San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-6627","authenticated-orcid":false,"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care and Department of Surgery NorthShore University Health System Evanston Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Lilly","family":"Zheng","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care and Department of Surgery NorthShore University Health System Evanston Illinois"},{"name":"Center for Cancer Genomics Wake Forest University School of Medicine Winston\u2010Salem North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Health Science Center at San Antonio San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Scott","family":"Lucia","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Colorado Denver School of Medicine Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Lippman","sequence":"additional","affiliation":[{"name":"Moores Cancer Center University of California San Diego La Jolla California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard L.","family":"Parnes","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention Department of Health and Human Services National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William B.","family":"Isaacs","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute and Department of Urology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo M.","family":"De Marzo","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute and Department of Urology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"},{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles G.","family":"Drake","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute and Department of Urology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"},{"name":"Department of Immunology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Department of Oncology Columbia University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Platz","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland"},{"name":"James Buchanan Brady Urological Institute and Department of Urology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(90)90487-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030660"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-13-1126"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0987"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23021"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23147"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-09-0256"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.55.12.1023"},{"key":"e_1_2_8_10_1","first-page":"3369","article-title":"Influence of cytokine gene polymorphisms on the development of prostate 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