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. 2023 Jan:179:76-86.
doi: 10.1016/j.ejca.2022.11.007. Epub 2022 Nov 13.

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease

Yue Jiao  1 , Thérèse Truong  2 , Séverine Eon-Marchais  1 , Noura Mebirouk  1 , Sandrine M Caputo  3 , Marie-Gabrielle Dondon  1 , Mojgan Karimi  2 , Dorothée Le Gal  1 , Juana Beauvallet  1 , Édith Le Floch  4 , Claire Dandine-Roulland  4 , Delphine Bacq-Daian  4 , Robert Olaso  4 , Juliette Albuisson  5 , Séverine Audebert-Bellanger  6 , Pascaline Berthet  7 , Valérie Bonadona  8 , Bruno Buecher  3 , Olivier Caron  9 , Mathias Cavaillé  10 , Jean Chiesa  11 , Chrystelle Colas  12 , Marie-Agnès Collonge-Rame  13 , Isabelle Coupier  14 , Capucine Delnatte  15 , Antoine De Pauw  3 , Hélène Dreyfus  16 , Sandra Fert-Ferrer  17 , Marion Gauthier-Villars  3 , Paul Gesta  18 , Sophie Giraud  19 , Laurence Gladieff  20 , Lisa Golmard  3 , Christine Lasset  8 , Sophie Lejeune-Dumoulin  21 , Mélanie Léoné  19 , Jean-Marc Limacher  22 , Alain Lortholary  23 , Élisabeth Luporsi  24 , Véronique Mari  25 , Christine M Maugard  26 , Isabelle Mortemousque  27 , Emmanuelle Mouret-Fourme  3 , Sophie Nambot  28 , Catherine Noguès  29 , Cornel Popovici  30 , Fabienne Prieur  31 , Pascal Pujol  14 , Nicolas Sevenet  32 , Hagay Sobol  30 , Christine Toulas  20 , Nancy Uhrhammer  33 , Dominique Vaur  7 , Laurence Venat  34 , Anne Boland-Augé  4 , Pascal Guénel  2 , Jean-François Deleuze  4 , Dominique Stoppa-Lyonnet  35 , Nadine Andrieu  1 , Fabienne Lesueur  36
Affiliations

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease

Yue Jiao et al. Eur J Cancer. 2023 Jan.

Abstract

Background: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors.

Objective: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study.

Results: All three PRS were associated with breast cancer in all studies, with odds ratios per standard deviation varying from 1.7 to 2.0 in CECILE and GENESIS, and hazard ratios varying from 1.1 to 1.4 in GEMO. The predictive performance of PRS313 in CECILE was similar to that reported in BCAC but lower than that in GENESIS (area under the receiver operating characteristic curve (AUC) = 0.67 and 0.75, respectively). PRS were less performant in BRCA2 and BRCA1 PV carriers (AUC = 0.58 and 0.54 respectively).

Conclusion: Our results are in line with previous validation studies in the general population and in BRCA1/2 PV carriers. Additionally, we showed that PRS may be of clinical utility for women with a strong family history of breast cancer and no BRCA1/2 PV, and for those carrying a predicted PV in a moderate-risk gene like ATM, CHEK2 or PALB2.

Keywords: BRCA1; BRCA2; Breast cancer; Genetic susceptibility; Polygenic risk score; Risk prediction; SNP.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DS-L and LG coordinated the genotyping of SNPs included in the PRS of the MammoRisk® test commercialized by Predilife until December 2021. This genotyping was performed in the Department of Genetics of the Institut Curie. All other authors declare no conflicts of interest.

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