Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results

Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results

Cancers

10.3390/cancers14112714

http://dx.doi.org/10.3390/cancers14112714

Seeu Si Ong, Peh Joo Ho, Alexis Jiaying Khng, Elaine Hsuen Lim, Fuh Yong Wong, Benita Kiat-Tee Tan, Swee Ho Lim, Ern Yu Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Rebecca Dent, Tira Jing Ying Tan, Joanne Ngeow, Preetha Madhukumar, Julie Liana Bte Hamzah, Yirong Sim, Geok Hoon Lim, Jinnie Siyan Pang, Veronica Siton Alcantara, Patrick Mun Yew Chan, Juliana Jia Chuan Chen, Sherwin Kuah, Jaime Chin Mui Seah, Shaik Ahmad Buhari, Siau Wei Tang, Celene Wei Qi Ng, Jingmei Li, Mikael Hartman

Cancer Research, oncology, Febrile neutropenia, Neutropenic fever, breast cancer, polygenic risk score, PRS

31 May 2022

Ong, S. S., Ho, P. J., Khng, A. J., Lim, E. H., Wong, F. Y., Tan, B. K.-T., Lim, S. H., Tan, E. Y., Tan, S.-M., Tan, V. K. M., Dent, R., Tan, T. J. Y., Ngeow, J., Madhukumar, P., Hamzah, J. L. B., Sim, Y., Lim, G. H., Pang, J. S., Alcantara, V. S., … Hartman, M. (2022). Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results. Cancers, 14(11), 2714. https://doi.org/10.3390/cancers14112714

Background: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. Methods: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. Results: PRS distributions were not significantly different in any of the comparisons. Higher PRSoverall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79–1.06]; FNc: 0.87 [0.73–1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRSER-pos) and ER-negative weighted PRS (PRSER-neg). Conclusion: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the National Research Foundation Singapore - NRF Fellowship
Grant Reference no. : NRF-NRFF2017-02

This research / project is supported by the National University of Singapore - NUS Start-up grant
Grant Reference no. : NA

This research / project is supported by the Saw Swee Hock School of Public Health - Research Seed Funding - Breast Cancer Prevention Programme
Grant Reference no. : SSHSPH-Res-Prog-BCPP

This research / project is supported by the Yong Loo Lin School of Medicine - Breast Cancer Screening and Prevention Programme
Grant Reference no. : NUHSRO/2020/121/BCSPP/LOA

This research / project is supported by the National Medical Research Council - NCIS Centre Grant
Grant Reference no. : NMRC/CG/NCIS/2010

This research / project is supported by the National Medical Research Council - Centre Grant Programme
Grant Reference no. : NMRC/CG/012/2013

This research / project is supported by the National Medical Research Council - Centre Grant Programme
Grant Reference no. : CGAug16M005

This research / project is supported by the National Medical Research Council - NMRC Clinician Scientist Award (SI Category)
Grant Reference no. : NMRC/CSA-SI/0015/2017

https://oar.a-star.edu.sg/communities-collections/articles/18924

2072-6694

Genome Institute of Singapore