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Genetic susceptibility to radiation-induced breast cancer after Hodgkin lymphoma.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Opstal-van Winden, Annemieke WJ 
de Haan, Hugoline G  ORCID logo  https://orcid.org/0000-0003-1126-4776
Hauptmann, Michael 
Schmidt, Marjanka K  ORCID logo  https://orcid.org/0000-0002-2228-429X
Broeks, Annegien 

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 4671 first primary breast cancer patients. Nine SNPs showed statistically significant interaction with RT on breast cancer risk (false discovery rate, <20%), of which 1 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 fourfold 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.

Description

Keywords

Adult, Aged, Aged, 80 and over, Breast Neoplasms, Cancer Survivors, Case-Control Studies, Female, Genetic Predisposition to Disease, Genotype, Hodgkin Disease, Humans, Middle Aged, Neoplasms, Radiation-Induced, Neoplasms, Second Primary, Odds Ratio, Polymorphism, Single Nucleotide, Quality Control, Radiotherapy Dosage, Regression Analysis, Risk, Young Adult

Journal Title

Blood

Conference Name

Journal ISSN

0006-4971
1528-0020

Volume Title

133

Publisher

American Society of Hematology

Rights

Publisher's own licence
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)