Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families


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Authors
Muranen, TA 
Khan, S 
Fagerholm, R 
Pelttari, L 
Abstract

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on ~4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.

Description
Keywords
breast cancer, common variants, hereditary, PRS, risk
Journal Title
Breast Cancer Research and Treatment
Conference Name
Journal ISSN
0167-6806
1573-7217
Volume Title
158
Publisher
Kluwer Academic Publishers
Sponsorship
European Commission (223175)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (A10710)
Cancer Research UK (A16563)
Cancer Research UK (A12014)
Cancer Research UK (A10118)
This work was supported by the Helsinki University Hospital Research Fund, the Finnish Cancer Society, the Nordic Cancer Union, the Academy of Finland [266528] and the Sigrid Juselius Foundation. The work of TAM has been supported by Finnish Cultural Foundation and Orion-Farmos Research Foundation. Genotyping of the iCOGS array, and the Breast Cancer Association Consortium, was supported by Cancer Research UK (C1287/A10118, C1287/A12014, C1287/A10710) and by the European Community’s Seventh Framework Programme under grant agreement n 223175 (HEALTH-F2-2009-223175) (COGS). NM was supported by Cancer Research UK (C1287/ C1287/A16563) and the PERSPECTIVE project, funded from the Government of Canada through Genome Canada and the Canadian Institutes of Health Research. AL was supported by Cancer Research UK.