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ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas
- Source :
- Gynecologic oncology, vol 131, iss 1, Johnatty, SE; Beesley, J; Gao, B; Chen, X; Lu, Y; Law, MH; et al.(2013). ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and the Cancer Genome Atlas. Gynecologic Oncology, 131(1), 8-14. doi: 10.1016/j.ygyno.2013.07.107. UCLA: Retrieved from: http://www.escholarship.org/uc/item/2p69d85p, Gynecologic Oncology; Vol 131
- Publication Year :
- 2013
- Publisher :
- Elsevier, 2013.
-
Abstract
- Objective\ud ABCB1 encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).\ud Methods\ud The best candidates from fine-mapping analysis of 21 ABCB1 SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.\ud Result\ud Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, ABCB1 expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.\ud Conclusion\ud Our study represents the largest analysis of ABCB1 SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.
- Subjects :
- Oncology
endocrine system diseases
Drug Resistance
Kaplan-Meier Estimate
Carcinoma, Ovarian Epithelial
Bioinformatics
Carboplatin
chemistry.chemical_compound
0302 clinical medicine
Neoplasms
Ovarian Epithelial
Antineoplastic Combined Chemotherapy Protocols
Obstetrics and Gynaecology
Genotype
2.1 Biological and endogenous factors
Neoplasms, Glandular and Epithelial
Aetiology
Cancer
P-glycoprotein
Outcome
Ovarian Neoplasms
0303 health sciences
biology
Glandular and Epithelial
Obstetrics and Gynecology
ABCB1
Single Nucleotide
Drug Resistance, Multiple
female genital diseases and pregnancy complications
3. Good health
Subfamily B
Paclitaxel
030220 oncology & carcinogenesis
Disease Progression
Female
Multiple
Australian Ovarian Cancer Study Group
Member 1
medicine.medical_specialty
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter
Oncology and Carcinogenesis
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Article
Disease-Free Survival
Paediatrics and Reproductive Medicine
03 medical and health sciences
Rare Diseases
Ovarian cancer
Internal medicine
medicine
Genetics
Humans
Chemotherapy
Oncology & Carcinogenesis
ATP Binding Cassette Transporter, Subfamily B, Member 1
Polymorphism
Gene
Proportional Hazards Models
030304 developmental biology
business.industry
Carcinoma
Human Genome
medicine.disease
chemistry
Drug Resistance, Neoplasm
Pharmacogenetics
biology.protein
Neoplasm
business
Polymorphisms
Subjects
Details
- Language :
- English
- ISSN :
- 00908258
- Database :
- OpenAIRE
- Journal :
- Gynecologic oncology, vol 131, iss 1, Johnatty, SE; Beesley, J; Gao, B; Chen, X; Lu, Y; Law, MH; et al.(2013). ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and the Cancer Genome Atlas. Gynecologic Oncology, 131(1), 8-14. doi: 10.1016/j.ygyno.2013.07.107. UCLA: Retrieved from: http://www.escholarship.org/uc/item/2p69d85p, Gynecologic Oncology; Vol 131
- Accession number :
- edsair.doi.dedup.....600c37541d08e950beb5a5ad0f92ff7d