{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:27:57Z","timestamp":1789165677741,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["b2008\u2010029\/LL\u2010LC"],"award-info":[{"award-number":["b2008\u2010029\/LL\u2010LC"]}],"id":[{"id":"10.13039\/501100006364","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":[[2021,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Single\u2010nucleotide polymorphisms (SNPs) in over 180 loci have been associated with breast cancer (BC) through genome\u2010wide association studies involving mostly unselected population\u2010based case\u2010control series. Some of them modify BC risk of women carrying a <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> (<jats:italic>BRCA1\/2<\/jats:italic>) mutation and may also explain BC risk variability in BC\u2010prone families with no <jats:italic>BRCA1\/2<\/jats:italic> mutation. Here, we assessed the contribution of SNPs of the iCOGS array in GENESIS consisting of BC cases with no <jats:italic>BRCA1<\/jats:italic>\/2 mutation and a sister with BC, and population controls. Genotyping data were available for 1281 index cases, 731 sisters with BC, 457 unaffected sisters and 1272 controls. In addition to the standard SNP\u2010level analysis using index cases and controls, we performed pedigree\u2010based association tests to capture transmission information in the sibships. We also performed gene\u2010 and pathway\u2010level analyses to maximize the power to detect associations with lower\u2010frequency SNPs or those with modest effect sizes. While SNP\u2010level analyses identified 18 loci, gene\u2010level analyses identified 112 genes. Furthermore, 31 Kyoto Encyclopedia of Genes and Genomes and 7 Atlas of Cancer Signaling Network pathways were highlighted (false discovery rate of 5%). Using results from the \u201cindex case\u2010control\u201d analysis, we built pathway\u2010derived polygenic risk scores (PRS) and assessed their performance in the population\u2010based CECILE study and in a data set composed of GENESIS\u2010affected sisters and CECILE controls. Although these PRS had poor predictive value in the general population, they performed better than a PRS built using our SNP\u2010level findings, and we found that the joint effect of family history and PRS needs to be considered in risk prediction models.<\/jats:p>","DOI":"10.1002\/ijc.33457","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T09:10:35Z","timestamp":1608887435000},"page":"1895-1909","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gene\u2010 and pathway\u2010level analyses of <scp>iCOGS<\/scp> variants highlight novel signaling pathways underlying familial breast cancer susceptibility"],"prefix":"10.1002","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-6992","authenticated-orcid":false,"given":"Christine","family":"Lonjou","sequence":"first","affiliation":[{"name":"Inserm, U900, Institut Curie  Paris France"},{"name":"Mines ParisTech  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