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Mavaddat, N.; Pharoah, P. D. P.; Michailidou, K.; Tyrer, J; Brook, M.N.; Bolla, M K; Wang, Q.; Dennis, J.; Dunning, A.M.; Shah, M.; Luben, R; Brown, J; Bojesen, S. E.; Nordestgaard, B. G.; Nielsen, S.F.; Flyger, H.; Czene, K.; Darabi, H; Eriksson, M; Peto, J; dos-Santos-Silva, I; Dudbridge, F; N. Johnson; Schmidt, M K; Broeks, A; Verhoef, S.; Rutgers, E. J.; Swerdlow, A.; Ashworth, A; Orr, N ... view all 212 authors View less authors (2015)
Publisher: Oxford University Press
Languages: English
Types: Article
Subjects:
Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at\ud different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical\ud evidence for genetic risk stratification is lacking.\ud Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk\ud stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible\ud pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and\ud by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK\ud incidence and mortality rates.\ud Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1%\ud of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds\ud ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95%\ud CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and\ud highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with\ud a first-degree family history of breast cancer.\ud Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The\ud observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may\ud be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this\ud report.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

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