Skip to main content
Erschienen in: Wiener klinische Wochenschrift 11-12/2017

01.06.2017 | original article

Influence of TS and ABCB1 gene polymorphisms on survival outcomes of 5‑FU-based chemotherapy in a Chinese population of advanced gastric cancer patients

verfasst von: Jun Chen, Xueming Ying, Ling Zhang, Xiaojun Xiang, Jianping Xiong

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 11-12/2017

Einloggen, um Zugang zu erhalten

Summary

To investigate the impacts of gene variations on survival outcomes of advanced gastric cancer (AGC) patients treated with 5‑fluorouracil (5-FU)-based chemotherapy, we analyzed the associations of 2 indels of the TS gene rs34743033 (double or triple tandem repeats of a 28 bp sequence in 5′-UTR, denoted as 2R or 3R allele) and rs16430 (a 6 bp variation at 1494 bp in 3′-UTR, denoted as ins6 or del6 allele) and 2 single nucleotide polymorphisms (SNPs) of ABCB1gene rs2032582 in exon 21 and rs1045642 in exon 26, with clinical outcomes after 5‑FU treatment. Generally, indels rs34743033 and rs16430 were genotyped by PCR and polyacrylamide gel electrophoresis assay and SNPs rs2032582 and rs1045642 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 110 Chinese AGC patients post-chemotherapy. Cox regression analysis was used to analyze the risk factors affecting patient survival. As a result, rs34743033, rs1045642 and rs2032582 were shown to be significantly associated with overall survival (P < 0.05), and associations between the four polymorphisms with disease-free survival were also observed (P < 0.05). Moreover, we found that genotypes rs34743033 3R/2R, rs16430 ins6/del6, rs1045642 CC or CT, and rs2032582 GG were beneficial predictors of clinical treatment outcome in AGC patients, suggesting some clinical implications in chemotherapy of a Chinese population.
Literatur
1.
Zurück zum Zitat Roder DM. The epidemiology of gastric cancer. Gastric Cancer. 2005;5:5–11.CrossRef Roder DM. The epidemiology of gastric cancer. Gastric Cancer. 2005;5:5–11.CrossRef
2.
Zurück zum Zitat Roukos DH. Extended (D2) lymph node dissection for gastric cancer: Do patients benefit? Ann Surg Oncol. 2000;7:7253–5. Roukos DH. Extended (D2) lymph node dissection for gastric cancer: Do patients benefit? Ann Surg Oncol. 2000;7:7253–5.
3.
Zurück zum Zitat Dickson JL, Cunningham D. Systemic treatment of gastric cancer. Eur J Gastroenterol Hepatol. 2004;16:255–63.CrossRefPubMed Dickson JL, Cunningham D. Systemic treatment of gastric cancer. Eur J Gastroenterol Hepatol. 2004;16:255–63.CrossRefPubMed
4.
Zurück zum Zitat Sadighi S, Mohagheghi MA, Montazeri A, Sadighi Z. Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5‑FU (TCF) with epirubicin, cisplatin, 5‑FU (ECF). BMC Cancer. 2006;6:6274.CrossRef Sadighi S, Mohagheghi MA, Montazeri A, Sadighi Z. Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5‑FU (TCF) with epirubicin, cisplatin, 5‑FU (ECF). BMC Cancer. 2006;6:6274.CrossRef
5.
Zurück zum Zitat Li QF, Yao RY, Liu KW, et al. Genetic polymorphism of GSTP1: prediction of clinical outcome to oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. J Korean Med Sci. 2010;25:846–52.CrossRefPubMedPubMedCentral Li QF, Yao RY, Liu KW, et al. Genetic polymorphism of GSTP1: prediction of clinical outcome to oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. J Korean Med Sci. 2010;25:846–52.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Carreras CW, Santi DV. The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem. 1995;64:64721–62.CrossRef Carreras CW, Santi DV. The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem. 1995;64:64721–62.CrossRef
7.
Zurück zum Zitat Graziani S, Bernauer J, Skouloubris S, et al. Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX. J Biol Chem. 2006;281:24048–57.CrossRefPubMed Graziani S, Bernauer J, Skouloubris S, et al. Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX. J Biol Chem. 2006;281:24048–57.CrossRefPubMed
8.
Zurück zum Zitat Toriumi F, Kubota T, Saikawa Y, et al. Thymidylate synthetase (TS) genotype and TS/dihydropyrimidine dehydrogenase mRNA level as an indicator in determining chemosensitivity to 5‑fluorouracil in advanced gastric carcinoma. Anticancer Res. 2004;24:2455–63.PubMed Toriumi F, Kubota T, Saikawa Y, et al. Thymidylate synthetase (TS) genotype and TS/dihydropyrimidine dehydrogenase mRNA level as an indicator in determining chemosensitivity to 5‑fluorouracil in advanced gastric carcinoma. Anticancer Res. 2004;24:2455–63.PubMed
9.
Zurück zum Zitat Lin D, Li H, Tan W, et al. Genetic polymorphisms in folate-metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development. Forum Nutr. 2007;60:140–5.CrossRefPubMed Lin D, Li H, Tan W, et al. Genetic polymorphisms in folate-metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development. Forum Nutr. 2007;60:140–5.CrossRefPubMed
10.
Zurück zum Zitat Ishibashi K, Sobajima J, Ishiguro T, et al. Expression of dihydropyrimidine dehydrogenase in primary colorectal cancer and liver metastasis – a relationship between mRNA levels in cancer cells and protein levels in cancerous tissue and effect of 5‑fluorouracil. Gan To Kagaku Ryoho. 2009;36:2232–5.PubMed Ishibashi K, Sobajima J, Ishiguro T, et al. Expression of dihydropyrimidine dehydrogenase in primary colorectal cancer and liver metastasis – a relationship between mRNA levels in cancer cells and protein levels in cancerous tissue and effect of 5‑fluorouracil. Gan To Kagaku Ryoho. 2009;36:2232–5.PubMed
11.
Zurück zum Zitat Orina JN, Calcagno AM, Wu CP, et al. Evaluation of current methods used to analyze the expression profiles of ATP-binding cassette transporters yields an improved drug-discovery database. Mol Cancer Ther. 2009;8:2057–66.CrossRefPubMedPubMedCentral Orina JN, Calcagno AM, Wu CP, et al. Evaluation of current methods used to analyze the expression profiles of ATP-binding cassette transporters yields an improved drug-discovery database. Mol Cancer Ther. 2009;8:2057–66.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Leschziner GD, Andrew T, Pirmohamed M, Johnson MR. ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research. Pharmacogenomics J. 2007;7:154–79.CrossRefPubMed Leschziner GD, Andrew T, Pirmohamed M, Johnson MR. ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research. Pharmacogenomics J. 2007;7:154–79.CrossRefPubMed
13.
Zurück zum Zitat Hung CC, Chen CC, Lin CJ, Liou HH. Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008;18:390–402.CrossRefPubMed Hung CC, Chen CC, Lin CJ, Liou HH. Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008;18:390–402.CrossRefPubMed
14.
Zurück zum Zitat Peethambaram P, Fridley BL, Vierkant RA, et al. Polymorphisms in ABCB1 and ERCC2 associated with ovarian cancer outcome. Int J Mol Epidemiol Genet. 2011;2:185–95.PubMedPubMedCentral Peethambaram P, Fridley BL, Vierkant RA, et al. Polymorphisms in ABCB1 and ERCC2 associated with ovarian cancer outcome. Int J Mol Epidemiol Genet. 2011;2:185–95.PubMedPubMedCentral
15.
Zurück zum Zitat Tian C, Ambrosone CB, Darcy KM, et al. Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol. 2012;124:575–81.CrossRefPubMed Tian C, Ambrosone CB, Darcy KM, et al. Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol. 2012;124:575–81.CrossRefPubMed
16.
Zurück zum Zitat Johnatty SE, Beesley J, Gao B, et al. ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: a comprehensive analysis from the Ovarian Cancer Association Consortium and the Cancer Genome Atlas. Gynecol Oncol. 2013;131:8–14.CrossRefPubMedPubMedCentral Johnatty SE, Beesley J, Gao B, et al. ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: a comprehensive analysis from the Ovarian Cancer Association Consortium and the Cancer Genome Atlas. Gynecol Oncol. 2013;131:8–14.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Baroudi O, Baroudi T, Omrane I, et al. Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5‑fluorouracil based chemotherapy treatment. Med Oncol. 2014;31:825.CrossRefPubMed Baroudi O, Baroudi T, Omrane I, et al. Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5‑fluorouracil based chemotherapy treatment. Med Oncol. 2014;31:825.CrossRefPubMed
18.
Zurück zum Zitat Zhu X, Zhao X, Peng W, et al. Epirubicin combined with oxaliplatin and 5‑day continuous infusion of 5‑fluorouracil as a first-line treatment for metastatic gastric cancer: treatment outcomes and analysis of prognostic factors. J Cancer Res Clin Oncol. 2015;141:109–18.CrossRefPubMed Zhu X, Zhao X, Peng W, et al. Epirubicin combined with oxaliplatin and 5‑day continuous infusion of 5‑fluorouracil as a first-line treatment for metastatic gastric cancer: treatment outcomes and analysis of prognostic factors. J Cancer Res Clin Oncol. 2015;141:109–18.CrossRefPubMed
19.
Zurück zum Zitat Blum M, Suzuki A, Ajani JA. A comprehensive review of S‑1 in the treatment of advanced gastric adenocarcinoma. Future Oncol. 2011;7:715–26.CrossRefPubMed Blum M, Suzuki A, Ajani JA. A comprehensive review of S‑1 in the treatment of advanced gastric adenocarcinoma. Future Oncol. 2011;7:715–26.CrossRefPubMed
20.
Zurück zum Zitat Ma Y, Tang L, Wang HX, et al. Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity. J Clin Pharm Ther. 2012;37:266–75.CrossRefPubMed Ma Y, Tang L, Wang HX, et al. Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity. J Clin Pharm Ther. 2012;37:266–75.CrossRefPubMed
21.
Zurück zum Zitat Jin Z, Jiang W, Wang L. Biomarkers for gastric cancer: progression in early diagnosis and prognosis (review). Oncol Lett. 2015;9(4):1502–8.PubMedPubMedCentral Jin Z, Jiang W, Wang L. Biomarkers for gastric cancer: progression in early diagnosis and prognosis (review). Oncol Lett. 2015;9(4):1502–8.PubMedPubMedCentral
22.
Zurück zum Zitat Durães C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Arch. 2014;464(3):367–78.CrossRefPubMed Durães C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Arch. 2014;464(3):367–78.CrossRefPubMed
23.
Zurück zum Zitat Emoto S, Ishigami H, Yamashita H, Yamaguchi H, Kaisaki S, Kitayama J. Clinical significance of CA125 and CA72-4 in gastric cancer with peritoneal dissemination. Gastric Cancer. 2012;15(2):154–61.CrossRefPubMed Emoto S, Ishigami H, Yamashita H, Yamaguchi H, Kaisaki S, Kitayama J. Clinical significance of CA125 and CA72-4 in gastric cancer with peritoneal dissemination. Gastric Cancer. 2012;15(2):154–61.CrossRefPubMed
26.
Zurück zum Zitat Wang S, Chen L, Zhao Q, et al. Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5‑fluorouracil-based postoperative adjuvant chemotherapy. Cancer Chemother Pharmacol. 2013;71:1073–82.CrossRefPubMed Wang S, Chen L, Zhao Q, et al. Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5‑fluorouracil-based postoperative adjuvant chemotherapy. Cancer Chemother Pharmacol. 2013;71:1073–82.CrossRefPubMed
27.
Zurück zum Zitat Lu ZM, Luo TH, Nie MM, et al. Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy. Tumour Biol. 2014;35:2941–8.CrossRefPubMed Lu ZM, Luo TH, Nie MM, et al. Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy. Tumour Biol. 2014;35:2941–8.CrossRefPubMed
28.
Zurück zum Zitat Kristensen MH, Weidinger M, Bzorek M, et al. Correlation between thymidylate synthase gene variants, RNA and protein levels in primary colorectal adenocarcinomas. J Int Med Res. 2010;38:484–97.CrossRefPubMed Kristensen MH, Weidinger M, Bzorek M, et al. Correlation between thymidylate synthase gene variants, RNA and protein levels in primary colorectal adenocarcinomas. J Int Med Res. 2010;38:484–97.CrossRefPubMed
29.
Zurück zum Zitat Mandola MV, Stoehlmacher J, Zhang W, et al. A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics. 2004;14:319–27.CrossRefPubMed Mandola MV, Stoehlmacher J, Zhang W, et al. A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics. 2004;14:319–27.CrossRefPubMed
30.
Zurück zum Zitat Fujishima M, Inui H, Hashimoto Y, et al. Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer. Anticancer Res. 2010;30:4373–9.PubMed Fujishima M, Inui H, Hashimoto Y, et al. Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer. Anticancer Res. 2010;30:4373–9.PubMed
31.
Zurück zum Zitat Vignoli M, Nobili S, Napoli C, et al. Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5‑fluorouracil. Pharmacol Res. 2011;64:242–8.CrossRefPubMed Vignoli M, Nobili S, Napoli C, et al. Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5‑fluorouracil. Pharmacol Res. 2011;64:242–8.CrossRefPubMed
32.
Zurück zum Zitat Arevalo E, Castanon E, Lopez I, et al. Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed. J Transl Med. 2014;12:98.CrossRefPubMedPubMedCentral Arevalo E, Castanon E, Lopez I, et al. Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed. J Transl Med. 2014;12:98.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Ishida Y, Kawakami K, Tanaka Y, et al. Association of thymidylate synthase gene polymorphism with its mRNA and protein expression and with prognosis in gastric cancer. Anticancer Res. 2002;22:2805–9.PubMed Ishida Y, Kawakami K, Tanaka Y, et al. Association of thymidylate synthase gene polymorphism with its mRNA and protein expression and with prognosis in gastric cancer. Anticancer Res. 2002;22:2805–9.PubMed
34.
Zurück zum Zitat Omar M, Crowe A, Parsons R, et al. P‑glycoprotein expression in Helicobacter pylori-positive patients: the influence of MDR1 C3435T polymorphism. J Dig Dis. 2012;13:414–20.CrossRefPubMed Omar M, Crowe A, Parsons R, et al. P‑glycoprotein expression in Helicobacter pylori-positive patients: the influence of MDR1 C3435T polymorphism. J Dig Dis. 2012;13:414–20.CrossRefPubMed
35.
Zurück zum Zitat Nakamura T. MDR1 genotypes related to pharmacokinetics and MDR1 expression. Yakugaku Zasshi. 2003;123:773–9.CrossRefPubMed Nakamura T. MDR1 genotypes related to pharmacokinetics and MDR1 expression. Yakugaku Zasshi. 2003;123:773–9.CrossRefPubMed
36.
Zurück zum Zitat Bonyadi MJ, Gerami SM, Somi MH, Khoshbaten M. Effect of the C3435T polymorphism of the multidrug resistance 1 gene on the severity of inflammatory bowel disease in Iranian Azeri Turks. Saudi J Gastroenterol. 2013;19:172–6.CrossRefPubMedPubMedCentral Bonyadi MJ, Gerami SM, Somi MH, Khoshbaten M. Effect of the C3435T polymorphism of the multidrug resistance 1 gene on the severity of inflammatory bowel disease in Iranian Azeri Turks. Saudi J Gastroenterol. 2013;19:172–6.CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Zhang D, Wang C, Zhou Z. Meta-analysis of ABCB1 3435C>T polymorphism and colorectal cancer. Pak J Med Sci. 2013;29:1269–74.PubMedPubMedCentral Zhang D, Wang C, Zhou Z. Meta-analysis of ABCB1 3435C>T polymorphism and colorectal cancer. Pak J Med Sci. 2013;29:1269–74.PubMedPubMedCentral
Metadaten
Titel
Influence of TS and ABCB1 gene polymorphisms on survival outcomes of 5‑FU-based chemotherapy in a Chinese population of advanced gastric cancer patients
verfasst von
Jun Chen
Xueming Ying
Ling Zhang
Xiaojun Xiang
Jianping Xiong
Publikationsdatum
01.06.2017
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 11-12/2017
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-016-1147-x

Weitere Artikel der Ausgabe 11-12/2017

Wiener klinische Wochenschrift 11-12/2017 Zur Ausgabe