title: ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy.
abstract: OBJECTIVE
  The human ABCB1 gene encodes P-glycoprotein, which transports a broad range of anticancer drugs, including paclitaxel. Although the functional consequences of ABCB1 polymorphisms have been the subject of numerous studies, few have assessed the association with clinical outcome.
  
  
  METHODS
  We assessed the association between the 2677G>T/A, 3435C>T, and 1236C>T ABCB1 polymorphisms and progression-free and overall survival in 309 patients from the Australian Ovarian Cancer Study treated with paclitaxel/carboplatin and subsequently tested significant observations in an independent validation set.
  
  
  RESULTS
  Women who carried the minor T/A alleles at the 2677G>T/A polymorphism were significantly less likely to relapse following treatment compared with homozygote GG carriers (P(Log-rank)=0.001) in the Australian Ovarian Cancer Study cohort. Subgroup analyses showed that this effect was limited to cases with residual disease <or=1 cm (P(Log-rank)=0.0004), not for those with residual disease >1 cm (P(Log-rank)=0.3). This effect was not confirmed in an independent validation set of carboplatin/paclitaxel-treated patients (n=278) using a higher residual disease cut point (<or=2 cm). However, analysis of the unrestricted data set expanded to include docetaxel-treated patients (n=914) did support an effect of the 2677T/A allele in patients with no macroscopic residual disease (hazard ratio, 0.70; 95% confidence interval, 0.46-1.04; P(one-sided)=0.039).
  
  
  CONCLUSIONS
  Our findings indicate that there is an effect of the 2677G>T/A polymorphism on progression-free survival in ovarian cancer patients who are treated with a taxane/carboplatin, which is dependent on the extent of residual disease, with a better prognosis for patients with the 2677T/A allele and minimal residual disease.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Johnatty
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beesley
authors.forename: Jim
authors.initials: J
authors.lastname: Paul
authors.forename: Sian
authors.initials: S
authors.lastname: Fereday
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.forename: Karen
authors.initials: K
authors.lastname: Byth
authors.forename: Sharon
authors.initials: S
authors.lastname: Marsh
authors.forename: Howard
authors.initials: H
authors.lastname: McLeod
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harnett
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.forename: Anna
authors.initials: A
authors.lastname: DeFazio
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench