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A case\u2013control study was designed (1,668 controls, 405 cases) in women aged 47\u201373\u2009years attending routine screening in Manchester UK, and enrolled in a wider study to assess methods for risk assessment. Risk from classical questionnaire risk factors was assessed using the Tyrer\u2013Cuzick model; mean percentage visual mammographic density was scored by two independent readers. DNA extracted from saliva was genotyped at selected SNPs using the OncoArray. A predefined polygenic risk score based on 143 SNPs was calculated (SNP143). The odds ratio (OR, and 95% confidence interval, CI) per interquartile range (IQ\u2010OR) of SNP143 was estimated unadjusted and adjusted for Tyrer\u2013Cuzick and breast density. Secondary analysis assessed risk by oestrogen receptor (ER) status. The primary polygenic risk score was well calibrated (O\/E OR 1.10, 95% CI 0.86\u20131.34) and accuracy was retained after adjustment for Tyrer\u2013Cuzick risk and mammographic density (IQ\u2010OR unadjusted 2.12, 95% CI% 1.75\u20132.42; adjusted 2.06, 95% CI 1.75\u20132.42). SNP143 was a risk factor for ER+ and ER\u2212 breast cancer (adjusted IQ\u2010OR, ER+ 2.11, 95% CI 1.78\u20132.51; ER\u2212 1.81, 95% CI 1.16\u20132.84). In conclusion, polygenic risk scores based on a large number of SNPs improve risk stratification in combination with classical risk factors and mammographic density, and SNP143 was similarly predictive for ER\u2010positive and ER\u2010negative disease.<\/jats:p>","DOI":"10.1002\/ijc.32541","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T16:35:06Z","timestamp":1561739706000},"page":"2122-2129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["A case\u2013control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density"],"prefix":"10.1002","volume":"146","author":[{"given":"Adam R.","family":"Brentnall","sequence":"first","affiliation":[{"name":"Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, Barts and The London Queen Mary University of London  London 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Manchester  Manchester United Kingdom"},{"name":"Manchester Academic Health Science Centre University of Manchester  Manchester United Kingdom"},{"name":"Manchester Breast Centre, Manchester Cancer Research Centre University of Manchester  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Sampson","sequence":"additional","affiliation":[{"name":"Prevention Breast Cancer Centre and Nightingale Breast Screening Centre University Hospital of South Manchester  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Howell","sequence":"additional","affiliation":[{"name":"Prevention Breast Cancer Centre and Nightingale Breast Screening Centre University Hospital of South Manchester  Manchester United Kingdom"},{"name":"The Christie NHS Foundation Trust  Manchester United Kingdom"},{"name":"Manchester Breast Centre, Manchester Cancer Research Centre University of Manchester  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