TY - JOUR
T1 - Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia
T2 - Null Results
AU - Ong, Seeu Si
AU - Ho, Peh Joo
AU - Khng, Alexis Jiaying
AU - Lim, Elaine Hsuen
AU - Wong, Fuh Yong
AU - Tan, Benita Kiat Tee
AU - Lim, Swee Ho
AU - Tan, Ern Yu
AU - Tan, Su Ming
AU - Tan, Veronique Kiak Mien
AU - Dent, Rebecca
AU - Tan, Tira Jing Ying
AU - Ngeow, Joanne
AU - Madhukumar, Preetha
AU - Hamzah, Julie Liana Bte
AU - Sim, Yirong
AU - Lim, Geok Hoon
AU - Pang, Jinnie Siyan
AU - Alcantara, Veronica Siton
AU - Chan, Patrick Mun Yew
AU - Chen, Juliana Jia Chuan
AU - Kuah, Sherwin
AU - Seah, Jaime Chin Mui
AU - Buhari, Shaik Ahmad
AU - Tang, Siau Wei
AU - Ng, Celene Wei Qi
AU - Li, Jingmei
AU - Hartman, Mikael
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - breast cancer
KW - febrile neutropenia
KW - neutropenic fever
KW - polygenic risk score
KW - PRS
UR - http://www.scopus.com/inward/record.url?scp=85131675549&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131675549&partnerID=8YFLogxK
U2 - 10.3390/cancers14112714
DO - 10.3390/cancers14112714
M3 - Article
AN - SCOPUS:85131675549
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 11
M1 - 2714
ER -
