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    A case-control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density

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    Authors
    Brentnall, A
    van Veen, E
    Harkness, E
    Rafiq, S
    Byers, H
    Astley, S
    Sampson, S
    Howell, Anthony
    Newman, W
    Cuzick, J
    Evans, D Gareth R
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    Affiliation
    Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, Barts and The London, Queen Mary University of London, London
    Issue Date
    2019
    
    Metadata
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    Abstract
    Panels of single nucleotide polymorphisms (SNPs) stratify risk for breast cancer in women from the general population, but studies are needed assess their use in a fully comprehensive model including classical risk factors, mammographic density and more than 100 SNPs associated with breast cancer. A case-control study was designed (1,668 controls, 405 cases) in women aged 47-73 years 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-Cuzick 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-OR) of SNP143 was estimated unadjusted and adjusted for Tyrer-Cuzick 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 0.86-1.34) and accuracy was retained after adjustment for Tyrer-Cuzick risk and mammographic density (IQ-OR unadjusted 2.12, 95% CI% 1.75-2.42; adjusted 2.06, 95% CI 1.75-2.42). SNP143 was a risk factor for ER+ and ER- breast cancer (adjusted IQ-OR, ER+ 2.11, 95% CI 1.78-2.51; ER- 1.81, 95% CI 1.16-2.84). 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-positive and ER-negative disease.
    Citation
    Brentnall AR, van Veen EM, Harkness EF, Rafiq S, Byers H, Astley SM, et al. A case-control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density. Int J Cancer. 2019.
    Journal
    International Journal of Cancer
    URI
    http://hdl.handle.net/10541/622052
    DOI
    10.1002/ijc.32541
    PubMed ID
    31251818
    Additional Links
    https://dx.doi.org/10.1002/ijc.32541
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1002/ijc.32541
    Scopus Count
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