Opstal-van Winden, A.W.J., de Haan, H.G. orcid.org/0000-0003-1126-4776, Hauptmann, M. et al. (27 more authors) (2019) Genetic susceptibility to radiation-induced breast cancer after Hodgkin Lymphoma. Blood, 133 (10). pp. 1130-1139. ISSN 0006-4971
Abstract
Female Hodgkin lymphoma (HL) patients treated with chest radiotherapy (RT) have a very high risk of breast cancer. The contribution of genetic factors to this risk is unclear. We therefore examined 211,155 germline single nucleotide polymorphisms (SNPs) for gene-radiation interaction on breast cancer risk in a case-only analysis including 327 breast cancer patients after chest RT for HL and 4,671 first primary breast cancer patients. Nine SNPs showed statistically significant interaction with RT on breast cancer risk (false discovery rate <20%), of which one SNP in the PVT1 oncogene attained the Bonferroni threshold for statistical significance. A polygenic risk score (PRS) composed of these SNPs (RT-interaction-PRS) and a previously published breast cancer PRS (BC-PRS) derived in the general population were evaluated in a case-control analysis comprising the 327 chest-irradiated HL patients with breast cancer and 491 chest-irradiated HL patients without breast cancer. Patients in the highest tertile of the RT-interaction-PRS had a 1.6-fold higher breast cancer risk than those in the lowest tertile. Remarkably, we observed a 4-fold increased RT-induced breast cancer risk in the highest compared with the lowest decile of the BC-PRS. On a continuous scale, breast cancer risk increased 1.4-fold per standard deviation of the BC-PRS, similar to the effect size found in the general population. This study demonstrates that genetic factors influence breast cancer risk after chest RT for HL. Given the high absolute breast cancer risk in radiation-exposed women, these results can have important implications for the management of current HL survivors and future patients.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 American Society of Hematology. This is an author produced version of a paper subsequently published in Blood. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Hodgkin lymphoma; radiotherapy; breast cancer; genetic susceptibility; polygenic risk score; single nucleotide polymorphisms |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Oncology (Sheffield) |
Funding Information: | Funder Grant number CANCER RESEARCH UK C9267/A25152 BREAST CANCER NOW TB2017SHEF |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Jan 2019 14:38 |
Last Modified: | 24 Nov 2021 14:33 |
Status: | Published |
Publisher: | American Society of Hematology |
Refereed: | Yes |
Identification Number: | 10.1182/blood-2018-07-862607 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140367 |