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ABCC2 polymorphisms and survival in the Princess Margaret cohort study and the NCIC clinical trials group BR.24 trial of platinum-treated advanced stage non-small cell lung cancer patients.
Cuffe, Sinead; Azad, Abul Kalam; Qiu, Xiaoping; Qiu, Xin; Brhane, Yonathan; Kuang, Qin; Marsh, Sharon; Savas, Sevtap; Chen, Zhuo; Cheng, Dangxiao; Leighl, Natasha B; Goss, Glenwood; Laurie, Scott A; Seymour, Lesley; Bradbury, Penelope A; Shepherd, Frances A; Tsao, Ming Sound; Chen, Bingshu E; Xu, Wei; Liu, Geoffrey.
Afiliación
  • Cuffe S; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada; HOPE Directorate, St James's Hospital, Dublin 8, Ireland. Electronic address: scuffe@stjames.ie.
  • Azad AK; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Qiu X; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Qiu X; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Brhane Y; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Kuang Q; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Marsh S; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
  • Savas S; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada; Discipline of Genetics, Memorial University of Newfoundland, St. John's, NL, Canada.
  • Chen Z; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Cheng D; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Leighl NB; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Goss G; Division of Medical Oncology, Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada.
  • Laurie SA; Division of Medical Oncology, Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada.
  • Seymour L; NCIC Clinical Trials Group, Queens University, Kingston, ON, Canada.
  • Bradbury PA; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada; NCIC Clinical Trials Group, Queens University, Kingston, ON, Canada.
  • Shepherd FA; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
  • Tsao MS; Department of Pathology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Chen BE; NCIC Clinical Trials Group, Queens University, Kingston, ON, Canada.
  • Xu W; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Liu G; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
Cancer Epidemiol ; 41: 50-6, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26816351
BACKGROUND: The drug transporter ABCC2 is upregulated in non-small cell lung cancer (NSCLC) and implicated in platinum resistance. We evaluated the association between germline polymorphisms in the ABCC2 gene and survival outcomes of platinum-treated advanced NSCLC patients. MATERIAL AND METHODS: Ten candidate and tagging germline polymorphisms in the ABCC2 gene were genotyped in a discovery cohort of 170 platinum-treated stage IV NSCLC patients from the Princess Margaret Cancer Centre. Associations with overall survival were assessed using multivariate Cox proportional hazard models adjusted for prognostic variables. To validate our results, we analyzed the association of the two top polymorphisms in the ABCC2 gene on survival outcomes of 219 stage IIIB-IV NSCLC patients enrolled on the NCIC Clinical Trials Group BR.24 clinical trial. RESULTS: Only one polymorphism was validated across both cohorts for an association with overall survival: the A allele of the ABCC2 polymorphism, rs8187710 (4544G>A), was associated with adverse overall survival (adjusted hazard ratio [aHR] 2.22; 95% CI: 1.2-4.0; p=0.009) among our stage IV NSCLC patients. A significant association with overall survival (aHR 1.73; 95% CI: 1.0-2.9; p=0.036) was observed for the same ABCC2 polymorphism in the BR.24 validation cohort. No other ABCC2 polymorphisms were associated with outcome. CONCLUSION: The ABCC2 polymorphism, rs8187710 (4544G>A), is associated with overall survival in platinum-treated advanced NSCLC patients. Additional studies are needed to evaluate the predictive versus prognostic nature of this relationship, and to explore the functional effect of this polymorphism on the pharmacokinetics of platinum drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Proteínas Asociadas a Resistencia a Múltiples Medicamentos / Neoplasias Pulmonares Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Epidemiol Asunto de la revista: EPIDEMIOLOGIA / NEOPLASIAS Año: 2016 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Proteínas Asociadas a Resistencia a Múltiples Medicamentos / Neoplasias Pulmonares Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Epidemiol Asunto de la revista: EPIDEMIOLOGIA / NEOPLASIAS Año: 2016 Tipo del documento: Article