Effects of genetic polymorphisms in the ABCB1 gene on clinical outcomes in patients with gastric cancer treated by second-line chemotherapy.
OBJECTIVE
Tumor cells that overexpress P-glycoprotein (Pgp) may be resistant to several anticancer agents due to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents. Pgp is encoded by the ATP binding cassette gene B1 (ABCB1). To our knowledge, only one previous report has evaluated the effect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer. The purpose of this analysis was to evaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advanced gastric cancer (AGC) treated with second-line chemotherapy.


METHODS
We retrospectively analyzed the impact of ABCB1 gene polymorphisms (ABCB1 3435C>T) on clinical outcomes in 100 patients with AGC who received second-line chemotherapy.


RESULTS
Median overall survival (OS) since the initiation of second-line chemotherapy was 6.0 months (95% confidence interval [CI], 4.8 to 8.0 months), and median progression-free survival (PFS) was 2.7 months (95% CI, 2.1 to 3.4 months). In a multivariate analysis of PFS, a 3435 CC polymorphism (n=45) was significantly associated with longer PFS compared with the CT/TT type polymorphism (n=55), with borderline significance (PFS of 3.2 months vs. 2.2 months, respectively; HR 1.50; 95% CI, 0.98-2.30; P = 0.061). ABCB1 3435 C>T polymorphisms were not associated with OS. No interaction was seen between ABCB1 polymorphisms and treatment regimens.


CONCLUSIONS
Genetic polymorphisms of ABCB1 3435C>T might have a possible impact on clinical outcomes of second-line chemotherapy in AGC. Further prospective evaluation using a larger sample size is required.
Shitara
Kohei
K
Department of Clinical Oncology, Aichi Cancer Center Hospital, Japan. Kouheis0824@yahoo.co.jp
Matsuo
Keitaro
K
Ito
Seiji
S
Sawaki
Akira
A
Kawai
Hiroki
H
Yokota
Tomoya
T
Takahari
Daisuke
D
Shibata
Takashi
T
Ura
Takashi
T
Ito
Hidemi
H
Hosono
Satoyo
S
Kawase
Takakazu
T
Watanabe
Miki
M
Tajima
Kazuo
K
Yatabe
Yasushi
Y
Tanaka
Hideo
H
Muro
Kei
K
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin