Association of the ABCB1 3435C&gt;T polymorphism and treatment outcomes in advanced gastric cancer patients treated with paclitaxel-based chemotherapy

Chung, Hyun Cheol

doi:10.3892/or_00000633

Cited by 15 publications

(23 citation statements)

References 25 publications

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“…Variants at the 3435 position have been associated with shorter overall survival and worse progression free survival in paclitaxel-treated cancer patients [8, 9]. Variants at the 3435 and 2677 position have been implicated in higher risk of paclitaxel-induced neutropenia [17] and docetaxel treatment outcomes [27].…”

Section: Discussionmentioning

confidence: 99%

“…A number of putative pharmacogenetic markers for paclitaxel outcomes, in breast cancer and in other solid tumors, have been evaluated [8-17]. Most of these studies focused on known mutations in biologically relevant candidate genes, such as CYP2C8, CYP3A4, and ABCB1, which code for the enzymes involved in paclitaxel metabolism and the transporters that influence paclitaxel disposition.…”

Section: Introductionmentioning

confidence: 99%

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CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel

Hertz

Motsinger‐Reif

Drobish³

et al. 2012

Breast Cancer Res Treat

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Paclitaxel is one of the most frequently used chemotherapeutic agents for the treatment of breast cancer patients. Using a candidate gene approach, we hypothesized that polymorphisms in genes relevant to the metabolism and transport of paclitaxel are associated with treatment efficacy and toxicity. Patient and tumor characteristics and treatment outcomes were collected prospectively for breast cancer patients treated with paclitaxel-containing regimens in the neoadjuvant setting. Treatment response was measured before and after each phase of treatment by clinical tumor measurement and categorized according to RECIST criteria, while toxicity data were collected from physician notes. The primary endpoint was achievement of clinical complete response (cCR) and secondary endpoints included clinical response rate (complete response + partial response) and grade 3+ peripheral neuropathy. The genotypes and haplotypes assessed were CYP1B1*3, CYP2C8*3, CYP3A4*1B/CYP3A5*3C, and ABCB1*2. A total of 111 patients were included in this study. Overall, cCR was 30.1 % to the paclitaxel component. CYP2C8*3 carriers (23/111, 20.7 %) had higher rates of cCR (55 % vs. 23 %; OR = 3.92 [95 % CI: 1.46–10.48], corrected p = 0.046). In the secondary toxicity analysis, we observed a trend toward greater risk of severe neuropathy (22 % vs. 8 %; OR = 3.13 [95 % CI: 0.89–11.01], uncorrected p = 0.075) in subjects carrying the CYP2C8*3 variant. Other polymorphisms interrogated were not significantly associated with response or toxicity. Patients carrying CYP2C8*3 are more likely to achieve clinical complete response from neoadjuvant paclitaxel treatment, but may also be at increased risk of experiencing severe peripheral neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel

Hertz

Motsinger‐Reif

Drobish³

et al. 2012

Breast Cancer Res Treat

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“…Two studies reported an association with survival in 43 Chinese gastric cancer patients [113] and in 109 Korean patients with metastatic breast cancer [114]. Conversely, for various types of cancer, no association with survival or the occurrence of adverse effects was observed [115][116][117].…”

Section: Taxanesmentioning

confidence: 92%

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

et al. 2015

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ATP-binding cassette transporter B1 (ABCB1; P-glycoprotein; multidrug resistance protein 1) is an adenosine triphosphate (ATP)-dependent efflux transporter located in the plasma membrane of many different cell types. Numerous structurally unrelated compounds, including drugs and environmental toxins, have been identified as substrates. ABCB1 limits the absorption of xenobiotics from the gut lumen, protects sensitive tissues (e.g. the brain, fetus and testes) from xenobiotics and is involved in biliary and renal secretion of its substrates. In recent years, a large number of polymorphisms of the ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1] gene have been described. The variants 1236C>T (rs1128503, p.G412G), 2677G>T/A (rs2032582, p.A893S/T) and 3435C>T (rs1045642, p.I1145I) occur at high allele frequencies and create a common haplotype; therefore, they have been most widely studied. This review provides an overview of clinical studies published between 2002 and March 2015. In summary, the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. Although polymorphisms and haplotypes of ABCB1 have been associated with alterations in drug disposition and drug response, including adverse events with various ABCB1 substrates in different ethnic populations, the results have been majorly conflicting, with limited clinical relevance. Future research activities are warranted, considering a deep-sequencing approach, as well as well-designed clinical studies with appropriate sample sizes to elucidate the impact of rare ABCB1 variants and their potential consequences for effect sizes.

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“…ABCB1 polymorphisms were also tested as predictive biomarkers for chemotherapy efficacy for irinotecan and oxaliplatin in 5-FU-based treatment colorectal cancer patients with negative results [19]. rs1045642 was found to be associated with clinical outcomes after chemotherapy of paclitaxel combined with 5-FU in 43 advanced gastric cancer patients [20]. In 5-FU or capecitabine-treated patients, increased toxicity has been related to increased efficacy, such as in the case of DPYD and TYMS deficiency [21,22].…”

Section: -I Ii-iv P-value 0-i Ii-iv P-value 0-i Ii-iv P-valuementioning

confidence: 98%

ABCB1 Gene Polymorphisms are Associated with Adverse Reactions in Fluoropyrimidine-Treated Colorectal Cancer Patients

et al. 2010

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Association of the ABCB1 3435C>T polymorphism and treatment outcomes in advanced gastric cancer patients treated with paclitaxel-based chemotherapy

Cited by 15 publications

References 25 publications

CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel

CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

ABCB1 Gene Polymorphisms are Associated with Adverse Reactions in Fluoropyrimidine-Treated Colorectal Cancer Patients

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