title: Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients.
abstract: Breast cancer is the most common cancer in women worldwide. Doxorubicin-based chemotherapy is used to treat breast cancer patients; however, neutropenia is a common hematologic side effect and can be life-threatening. The ABCB1 and SLC22A16 genes encode proteins that are essential for doxorubicin transport. In this study, we explored the effect of 2 common polymorphisms in ABCB1 (rs10276036 C/T) and SLC22A16 (rs12210538 A/G) on the development of grade 3/4 febrile neutropenia in Iranian breast cancer patients. Our results showed no significant association between these polymorphisms and grade 3/4 febrile neutropenia; however, allele C of ABCB1 (rs10276036 C/T) (p = 0.315, OR = 1.500, 95% CI = 0.679-3.312) and allele A of SLC22A16 (rs12210538 A/G) (p = 0.110, OR = 2.984, 95% CI = 0.743-11.988) tended to have a greater association with grade 3/4 febrile neutropenia, whereas allele T of ABCB1 (rs10276036) (p = 0.130, OR = 0.515, 95% CI = 0.217-1.223) and allele G of SLC22A16 (rs12210538) (p = 0.548, OR = 0.786, 95% CI = 0.358-1.726) tended to protect against this condition. In addition to breast cancer, a statistically significant association was also observed between the development of grade 3/4 febrile neutropenia and other clinical manifestations such as stage IIIC cancer (p = 0.037) and other diseases (p = 0.026). Our results indicate that evaluation of the risk of grade 3/4 neutropenia development and consideration of molecular and clinical findings may be of value when screening for high-risk breast cancer patients.
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Faraji
authors.affiliation: Department of Radiation Oncology, 7-Tir Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Dehghan Manshadi
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mobaraki
authors.affiliation: Department of Radiation Oncology, 7-Tir Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahkameh
authors.initials: M
authors.lastname: Zare
authors.affiliation: Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D064147:Febrile Neutropenia / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D007492:Iran; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D027701:Organic Cation Transport Proteins; C467737:SLC22A16 protein, human; D004317:Doxorubicin