Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients

Yin, Ji‐Ye; Huang, Qiong; Zhao, Ying; Zhou, Hong; Liu, Zhao‐Qian

doi:10.1371/journal.pone.0038150

Cited by 46 publications

(37 citation statements)

References 66 publications

(61 reference statements)

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“…Our previous studies showed that genetic polymorphisms were useful clinical markers for chemotherapy response and toxicity prediction in lung cancer patients [9, 27–29]. To investigate the relationship between MMR pathway genetic polymorphisms and platinum-induced toxicity, we evaluated 6 MMR genes ( MLH1 , MSH2 , MSH3 , MSH4 , MSH5 , and MSH6 ) in Chinese NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

et al. 2017

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BackgroundChemotherapy toxicity is a serious problem from which non-small cell lung cancer (NSCLC) patients suffer. The mismatch repair (MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients. In this study, we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.MethodsA total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study. Toxicity was evaluated in each patient after two cycles of chemotherapy. A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.ResultsMutS homolog 2 (MSH2) rs6544991 [odds ratio (OR) 2.98, 95% confidence interval (CI) 1.20–7.40, P = 0.019] was associated with gastrointestinal toxicity in the dominant model; MSH3 rs6151627 (OR 2.38, 95% CI 1.23–4.60, P = 0.010), rs6151670 (OR 2.05, 95% CI 1.07–3.93, P = 0.031), and rs7709909 (OR 2.38, 95% CI 1.23–4.64, P = 0.010) were associated with hematologic toxicity in the dominant model. Additionally, MSH5 rs805304 was significantly associated with overall toxicity (OR 2.21, 95% CI 1.19–4.09, P = 0.012), and MSH5 rs707939 was significantly associated with both overall toxicity (OR 0.42, 95% CI 0.23–0.76, P = 0.004) and gastrointestinal toxicity (OR 0.44, 95% CI 0.20–0.96, P = 0.038) in the dominant model.ConclusionGenetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40880-016-0175-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

et al. 2017

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“…There were two meta-analyses which reported the inconsistent results for evaluating the associations between GSTP1 and GSTM1 polymorphisms and response to platinum-based chemotherapy in lung cancer 17, 40 . These two meta-analyses have not enrolled update studies and just analyzed a few studies, and thus may have biased conclusions.…”

Section: Introductionmentioning

confidence: 99%

Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients

Shao

Shi

et al. 2017

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The influences of glutathione s-transferase P1, M1, and T1 variants on the efficacy of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients were inconsistent in previous studies. Our meta-analysis enrolled 31 publications including 5712 patients and provided more convincing and reliable conclusions. Results showed that GSTP1 IIe105Val IIe/Val and Val/Val Asian patients were more likely to have better response rates compared to IIe/IIe patients (odds ratio (OR) = 1.592, 95% confidence intervals (CIs), 1.087–2.332, P = 0.017). The Asian patients bearing the favorable GSTM1 null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorable GSTM1 present genotype (OR = 1.493 (1.192–1.870), P < 0.001). Caucasian lung cancer patients bearing GSTT1 null genotype might be more closely associated with shorter survival time and higher risks of death than the GSTT1 present patients (hazard ratio (HR) = 1.423, CI = 1.084–1.869, P = 0.011). Our meta-analysis suggested that the GSTP1 IIe105Val, GSTM1 and GSTT1 null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use of GSTP1 IIe105Val, GSTM1 and GSTT1 null polymorphisms as predictive factors of efficacy of personalized platinum-based chemotherapy to NSCLC patients requires further verification with multi-center, multi-ethnic and large-sample-size pharmacogenetic studies.

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“…5 There is accumulating evidence to support the hypothesis that genetic polymorphisms alter drug response and survival. [6][7][8][9][10][11] Cytochrome P450 (CYP) is a superfamily of phase I oxidation enzymes, the first 3 families of which metabolize xenobiotics such as environmental carcinogens and various drugs (Table 1) including antineoplastic drugs (Table 2). [12][13][14][15][16] They are also involved in drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P-450 Polymorphisms and Clinical Outcome in Patients with Non-Small Cell Lung Cancer

İşcan

Ada

2017

tjps

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ÖZAkciğer kanseri dünyada artan bir sağlık sorunudur. Akciğer kanseri hastalarının çoğu küçük hücreli dışı akciğer kanseridir (KHDAK). Bu hastalar genelde ilk basamakta standart platin bazlı kemoterapi ile tedavi olmaktadır. Bu hastalarda kemoterapiye yanıt ise düşük düzeyde olmakta ve tedaviye yanıtta bireyler arasında büyük farklılıklar görülmektedir. Genetik polimorfizmlerin ilaca karşı alınan yanıt ile sağkalım üzerinde etkili olduğu hipotezini destekleyen kanıtlar giderek artmaktadır. Sitokrom P450 (CYP) enzimleri antineoplastik ilaçları metabolize etmekte ve ilaç direncine neden olabilmektedir. Polimorfik CYP'lerin enzim aktiviteleri değişkenlik göstermekte ve dolayısıyla akciğer kanseri hastalarının kemoterapiye yanıtlarında ve sağkalım süreleri üzerinde etkileri olabilmektedirler. Bu derlemede, özellikle platin bazlı kemoterapi alan KHDAK hastalarının prognozunda klinisyenlere yararlı olabilecek, CYP1A1, CYP1B1, CYP2D6, CYP2E1 ve CYP3A4 gen polimorfizmlerinin bu tedaviyi alan KHDAK hastalarının kemoterapiye yanıt ve sağkalım süreleri üzerindeki etkileri ile ilgili olarak son yıllarda elde edilen bulgular ortaya konmaktadır. Anahtar kelimeler: CYP, polimorfizm, kemoterapiye yanıt, sağkalım, akciğer kanseri Lung cancer is an increasing worldwide public health problem. Most patients with lung cancer have non-small cell lung cancer (NSCLC). These patients are mainly treated with standard platinum-based chemotherapy. Poor response and great inter-individual variety in treatment response occurs among these patients. There is accumulating evidence to support the hypothesis that genetic polymorphisms alter the drug response and survival. Cytochrome P450 (CYP) enzymes metabolize antineoplastic drugs and are involved in drug resistance. Polymorphic CYPs have altered enzyme activities and thus they may influence the response to chemotherapy and survival in patients with lung cancer. In the current review, recent findings with respect to the role of mainly CYP1A1, CYP1B1, CYP2D6, CYP2E1 and CYP3A4 gene polymorphisms in response to chemotherapy and survival in patients with NSCLC have been provided, which could be useful for clinicians in the prognosis of these patients who are mainly treated with platinum-based chemotherapy.

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Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients

Cited by 46 publications

References 66 publications

Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients

Cytochrome P-450 Polymorphisms and Clinical Outcome in Patients with Non-Small Cell Lung Cancer

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