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ABSTRACT: 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.
SUBMITTER: Ong SS
PROVIDER: S-EPMC9179461 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Ong Seeu Si SS Ho Peh Joo PJ Khng Alexis Jiaying AJ Lim Elaine Hsuen EH Wong Fuh Yong FY Tan Benita Kiat-Tee BK Lim Swee Ho SH Tan Ern Yu EY Tan Su-Ming SM Tan Veronique Kiak Mien VKM Dent Rebecca R Tan Tira Jing Ying TJY Ngeow Joanne J Madhukumar Preetha P Hamzah Julie Liana Bte JLB Sim Yirong Y Lim Geok Hoon GH Pang Jinnie Siyan JS Alcantara Veronica Siton VS Chan Patrick Mun Yew PMY Chen Juliana Jia Chuan JJC Kuah Sherwin S Seah Jaime Chin Mui JCM Buhari Shaik Ahmad SA Tang Siau Wei SW Ng Celene Wei Qi CWQ Li Jingmei J Hartman Mikael M
Cancers 20220531 11
<h4>Background</h4>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.<h4>Methods</h4>This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutr ...[more]