Top

Published in:

01-12-2021 | Gastric Cancer | Research

A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer

Authors: Miguel Cordova-Delgado, María Loreto Bravo, Elisa Cumsille, Charlotte N. Hill, Matías Muñoz-Medel, Mauricio P. Pinto, Ignacio N. Retamal, María A. Lavanderos, Juan Francisco Miquel, Maria Rodriguez-Fernandez, Yuwei Liao, Zhiguang Li, Alejandro H. Corvalán, Ricardo Armisén, Marcelo Garrido, Luis A. Quiñones, Gareth I. Owen

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity.

Methods

Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms.

Results

Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity.

Conclusion

Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.

Available only for authorised users

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.CrossRefPubMed

Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, et al. Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 2014;50(7):1330–44. https://doi.org/10.1016/j.ejca.2014.01.029.CrossRefPubMed

de la Jara JJ, Bastias G, Ferreccio C, Moscoso C, Sagues S, Cid C, et al. A snapshot of cancer in Chile: analytical frameworks for developing a cancer policy. Biol Res. 2015;48:10.CrossRef

Owen GI, Pinto MP, Retamal IN, Fernádez MF, Cisternas B, Mondaca S, et al. Chilean Gastric Cancer Task Force: A study protocol to obtain a clinical and molecular classification of a cohort of gastric cancer patients. Medicine (Baltimore). 2018;97:e0419.CrossRef

Carmona-Bayonas A, Jiménez-Fonseca P, Lorenzo MLS, Ramchandani A, Martínez EA, Custodio A, et al. On the effect of triplet or doublet chemotherapy in advanced gastric Cancer: results from a National Cancer Registry. J Natl Compr Cancer Netw. 2016;14(11):1379–88. https://doi.org/10.6004/jnccn.2016.0148.CrossRef

Park H, Jin RU, Wang-Gillam A, Suresh R, Rigden C, Amin M, et al. FOLFIRINOX for the treatment of advanced Gastroesophageal cancers: a phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6(8):1231–40. https://doi.org/10.1001/jamaoncol.2020.2020.CrossRefPubMed

Schwab M, Zanger UM, Marx C, Schaeffeler E, Klein K, Dippon J, et al. Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU toxicity study group. J Clin Oncol. 2008;26(13):2131–8. https://doi.org/10.1200/JCO.2006.10.4182.CrossRefPubMed

Lopez Sobella M, Criado Illana MT, Esteban Herrera B, Lopez Arranza MC. Severe 5-fluorouracil induced toxicity associated with dihydropyrimidine dehydrogenase deficiency. Farm Hosp. 2008;32(1):54–6. http://www.ncbi.nlm.nih.gov/pubmed/18426703. https://doi.org/10.1016/s1130-6343(08)72810-1.CrossRefPubMed

Pachman DR, Qin R, Seisler DK, Smith EM, Beutler AS, Ta LE, et al. Clinical course of Oxaliplatin-induced neuropathy: results from the randomized phase III trial N08CB (alliance). J Clin Oncol. 2015;33(30):3416–22. https://doi.org/10.1200/JCO.2014.58.8533.CrossRefPubMedPubMedCentral

10.

Erichsen HC, Chanock SJ. SNPs in cancer research and treatment. Br J Cancer. 2004;90(4):747–51. https://doi.org/10.1038/sj.bjc.6601574.CrossRefPubMedPubMedCentral

11.

Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–91.CrossRefPubMed

12.

López-Cortés A, Guerrero S, Redal MA, Alvarado AT, Quiñones LA. State of art of Cancer pharmacogenomics in Latin American populations. Int J Mol Sci. 2017;18(6). https://doi.org/10.3390/ijms18060639.

13.

Quiñones L, Roco Á, Cayún JP, Escalante P, Miranda C, Varela N, et al. Clinical applications of pharmacogenomics. Rev Med Chil. 2017;145(4):483–500. https://doi.org/10.4067/S0034-98872017000400009.CrossRefPubMed

14.

Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526(7573):343–50. https://doi.org/10.1038/nature15817.CrossRefPubMedPubMedCentral

15.

Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov. 2005;4(4):307–20. https://doi.org/10.1038/nrd1691.CrossRefPubMed

16.

Sakaeda T, Nakamura T, Okumura K. MDR1 genotype-related pharmacokinetics and pharmacodynamics. Biol Pharm Bull. 2002;25(11):1391–400. http://www.ncbi.nlm.nih.gov/pubmed/12419946. https://doi.org/10.1248/bpb.25.1391.CrossRefPubMed

17.

Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer. 2006;6(7):546–58. https://doi.org/10.1038/nrc1887.CrossRefPubMed

18.

Sun Y, Pan J, Tong X, Chen E, Yan W, Wu M, et al. Glutathione S-transferases genes variants and chemotherapy efficacy in gastrointestinal cancer patients: a meta-analysis based on 50 pharmacogenetic studies. J Cancer. 2019;10(13):2915–26. https://doi.org/10.7150/jca.31130.CrossRefPubMedPubMedCentral

19.

Marsh S, McLeod H, Dolan E, Shukla SJ, Rabik CA, Gong L, et al. Platinum pathway. Pharmacogenet Genomics. 2009;19(7):563–4. https://doi.org/10.1097/FPC.0b013e32832e0ed7.CrossRefPubMedPubMedCentral

20.

Palmirotta R, Carella C, Silvestris E, Cives M, Stucci SL, Tucci M, et al. SNPs in predicting clinical efficacy and toxicity of chemotherapy: walking through the quicksand. Oncotarget. 2018;9:25355–82. https://doi.org/10.18632/oncotarget.25256.CrossRefPubMedPubMedCentral

21.

Roco A, Cayún J, Contreras S, Stojanova J, Quiñones L. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy? Front Genet. 2014;5:391. https://doi.org/10.3389/fgene.2014.00391.CrossRefPubMedPubMedCentral

22.

Arnould S, Hennebelle I, Canal P, Bugat R, Guichard S. Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines. Eur J Cancer. 2003;39(1):112–9. https://doi.org/10.1016/S0959-8049(02)00411-2.CrossRefPubMed

23.

Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–8. https://doi.org/10.1038/nrc1074.CrossRefPubMed

24.

Panczyk M. Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years. World J Gastroenterol. 2014;20(29):9775–827. https://doi.org/10.3748/wjg.v20.i29.9775.CrossRefPubMedPubMedCentral

25.

Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989;16(4):215–37. https://doi.org/10.2165/00003088-198916040-00002.CrossRefPubMed

26.

Dhelens C, Bonadona A, Thomas F, Chapuis C, Potton L, Marsili S, et al. Lethal 5-fluorouracil toxicity in a colorectal patient with severe dihydropyrimidine dehydrogenase (DPD) deficiency. Int J Color Dis. 2016;31(3):699–701. https://doi.org/10.1007/s00384-015-2191-0.CrossRef

27.

Van Kuilenburg AB, Meinsma R, Zoetekouw L, Van Gennip AH. Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the IVS14+1g>a mutation. Int J Cancer. 2002;101(3):253–8. https://doi.org/10.1002/ijc.10599.CrossRefPubMed

28.

Maring JG, van Kuilenburg AB, Haasjes J, Piersma H, Groen HJ, Uges DR, et al. Reduced 5-FU clearance in a patient with low DPD activity due to heterozygosity for a mutant allele of the DPYD gene. Br J Cancer. 2002;86(7):1028–33. https://doi.org/10.1038/sj.bjc.6600208.CrossRefPubMedPubMedCentral

29.

Jakobsen A, Nielsen JN, Gyldenkerne N, Lindeberg J. Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. J Clin Oncol. 2005;23(7):1365–9. https://doi.org/10.1200/JCO.2005.06.219.CrossRefPubMed

30.

Amstutz U, Henricks LM, Offer SM, Barbarino J, Schellens JHM, Swen JJ, et al. Clinical Pharmacogenetics implementation consortium (CPIC) guideline for Dihydropyrimidine dehydrogenase genotype and Fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018;103(2):210–6. https://doi.org/10.1002/cpt.911.CrossRefPubMed

31.

Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–43. https://doi.org/10.1038/s41586-020-2308-7.CrossRefPubMedPubMedCentral

32.

Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. https://doi.org/10.1038/nature15393.CrossRefPubMed

33.

Shimoyama S. Pharmacogenetics of fluoropyrimidine and cisplatin. A future application to gastric cancer treatment. J Gastroenterol Hepatol. 2009;24(6):970–81. https://doi.org/10.1111/j.1440-1746.2009.05856.x.CrossRefPubMed

34.

Toffoli G, Cecchin E. Pharmacogenetics and stomach cancer: an update. Pharmacogenomics. 2007;8(5):497–505. https://doi.org/10.2217/14622416.8.5.497.CrossRefPubMed

35.

Patel JN, Fuchs CS, Owzar K, Chen Z, McLeod HL. Gastric cancer pharmacogenetics: progress or old tripe? Pharmacogenomics. 2013;14(9):1053–64. https://doi.org/10.2217/pgs.13.88.CrossRefPubMed

36.

Milano G, Etienne MC, Cassuto-Viguier E, Thyss A, Santini J, Frenay M, et al. Influence of sex and age on fluorouracil clearance. J Clin Oncol Off J Am Soc Clin Oncol. 1992;10(7):1171–5. https://doi.org/10.1200/JCO.1992.10.7.1171.CrossRef

37.

Sloan JA, Goldberg RM, Sargent DJ, Vargas-Chanes D, Nair S, Cha SS, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(6):1491–8. https://doi.org/10.1200/JCO.2002.20.6.1491.CrossRef

38.

Davidson M, Wagner AD, Kouvelakis K, Nanji H, Starling N, Chau I, et al. Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric cancer: a pooled analysis of four randomised trials. Eur J Cancer. 2019;121:40–7. https://doi.org/10.1016/j.ejca.2019.08.010.CrossRefPubMed

39.

Yin J-Y, Li X, Li X-P, Xiao L, Zheng W, Chen J, et al. Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients. Cancer Lett. 2016;377(1):65–73. https://doi.org/10.1016/j.canlet.2016.04.029.CrossRefPubMed

40.

Anandi P, Dickson AL, Feng Q, Wei W-Q, Dupont WD, Plummer D, et al. Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice. Pharmacogenomics J. 2020. https://doi.org/10.1038/s41397-020-0163-4.

41.

Lavanderos MA, Cayún JP, Roco Á, Sandoval C, Cerpa L, Rubilar JC, et al. Association study among candidate genetic polymorphisms and chemotherapy-related severe toxicity in testicular Cancer patients. Frontiers in Pharmacology. 2019;10:206 https://www.frontiersin.org/article/10.3389/fphar.2019.00206.CrossRefPubMedPubMedCentral

42.

Cordova-Delgado M, Pinto MP, Retamal IN, Munoz-Medel M, Bravo ML, Fernandez MF, et al. High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study. Cancers (Basel). 2019;11. https://doi.org/10.3390/cancers11091275.

43.

Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9. https://doi.org/10.1093/bioinformatics/btl268.CrossRefPubMed

44.

Menard S. Coefficients of determination for multiple logistic regression analysis. Am Stat. 2000;54(1):17–24. https://doi.org/10.1080/00031305.2000.10474502.CrossRef

45.

Han J, Kamber M, Pei J. 8 - Classification: Basic Concepts. In: Han J, Kamber M, Pei JBT-DM, Third E, editors. The Morgan Kaufmann Series in Data Management Systems. Boston: Morgan Kaufmann; 2012. p. 327–391. https://doi.org/10.1016/B978-0-12-381479-1.00008-3.CrossRef

46.

Kuhn M. Building Predictive Models in R Using the caret Package. J Stat Software. 2008;1(5). https://doi.org/10.18637/jss.v028.i05.

47.

Zhang Z, Kattan MW. Drawing Nomograms with R: applications to categorical outcome and survival data. Ann Transl Med. 2017;5:211. https://doi.org/10.21037/atm.2017.04.01.CrossRefPubMedPubMedCentral

48.

Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012;92(4):414–7. https://doi.org/10.1038/clpt.2012.96.CrossRefPubMed

49.

Sunyaev S, Ramensky V, Koch I, Lathe W 3rd, Kondrashov AS, Bork P. Prediction of deleterious human alleles. Hum Mol Genet. 2001;10(6):591–7. http://www.ncbi.nlm.nih.gov/pubmed/11230178. https://doi.org/10.1093/hmg/10.6.591.CrossRefPubMed

50.

Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31(13):3812–4. http://www.ncbi.nlm.nih.gov/pubmed/12824425. https://doi.org/10.1093/nar/gkg509.CrossRefPubMedPubMedCentral

51.

Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr. 1974;19(6):716–23. https://doi.org/10.1109/TAC.1974.1100705.CrossRef

52.

Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed

53.

Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.CrossRefPubMed

54.

Wilke H, Muro K, Van Cutsem E, Oh S-C, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–35. https://doi.org/10.1016/S1470-2045(14)70420-6.CrossRefPubMed

55.

Kang Y-K, Boku N, Satoh T, Ryu M-H, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71.CrossRefPubMed

56.

Wörmann B, Bokemeyer C, Burmeister T, Köhne C-H, Schwab M, Arnold D, et al. Dihydropyrimidine dehydrogenase testing prior to treatment with 5-fluorouracil, Capecitabine, and Tegafur: a consensus paper. Oncol Res Treat. 2020;43(11):628–36. https://doi.org/10.1159/000510258.CrossRefPubMed

57.

Zhou Y, Dagli Hernandez C, Lauschke VM. Population-scale predictions of DPD and TPMT phenotypes using a quantitative pharmacogene-specific ensemble classifier. Br J Cancer. 2020;123(12):1782–9. https://doi.org/10.1038/s41416-020-01084-0.CrossRefPubMedPubMedCentral

58.

Nugent A, Conatser KR, Turner LL, Nugent JT, Sarino EMB, Ricks-Santi LJ. Reporting of race in genome and exome sequencing studies of cancer: a scoping review of the literature. Genet Med. 2019;21(12):2676–80. https://doi.org/10.1038/s41436-019-0558-2.CrossRefPubMedPubMedCentral

59.

Okada E, Ukawa S, Nakamura K, Hirata M, Nagai A, Matsuda K, et al. Demographic and lifestyle factors and survival among patients with esophageal and gastric cancer: the biobank Japan project. J Epidemiol. 2017;27(3):S29–35. https://doi.org/10.1016/j.je.2016.12.002.CrossRefPubMedPubMedCentral

60.

Gonzalez-Hormazabal P, Musleh M, Bustamante M, Stambuk J, Pisano R, Valladares H, et al. Polymorphisms in RAS/RAF/MEK/ERK Pathway Are Associated with Gastric Cancer. Genes (Basel). 2018;10. https://doi.org/10.3390/genes10010020.

61.

Zong L, Abe M, Seto Y, Ji J. The challenge of screening for early gastric cancer in China. Lancet. 2016;388:2606.CrossRefPubMed

62.

Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(18):2903–9. https://doi.org/10.1200/JCO.2005.05.0245.CrossRef

63.

Trumper M, Ross PJ, Cunningham D, Norman AR, Hawkins R, Seymour M, et al. Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: a pooled analysis of three clinical trials. Eur J Cancer. 2006;42(7):827–34. https://doi.org/10.1016/j.ejca.2005.08.044.CrossRefPubMed

64.

Visa L, Jiménez-Fonseca P, Martínez EA, Hernández R, Custodio A, Garrido M, et al. Efficacy and safety of chemotherapy in older versus non-older patients with advanced gastric cancer: a real-world data, non-inferiority analysis. J Geriatr Oncol. 2018;9(3):254–64. https://doi.org/10.1016/j.jgo.2017.11.008.CrossRefPubMed

65.

Jatoi A, Foster NR, Egner JR, Burch PA, Stella PJ, Rubin J, et al. Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: a pooled analysis of eight consecutive north central Cancer treatment group (NCCTG) trials. Int J Oncol. 2010;36(3):601–6. https://doi.org/10.3892/ijo_00000535.CrossRefPubMed

66.

Slagter AE, Tudela B, van Amelsfoort RM, Sikorska K, van Sandick JW, van de Velde CJH, et al. Older versus younger adults with gastric cancer receiving perioperative treatment: results from the CRITICS trial. Eur J Cancer. 2020;130:146–54. https://doi.org/10.1016/j.ejca.2020.02.008.CrossRefPubMed

67.

Cristina V, Mahachie J, Mauer M, Buclin T, Van Cutsem E, Roth A, et al. Association of Patient sex with Chemotherapy-Related Toxic Effects: a retrospective analysis of the PETACC-3 trial conducted by the EORTC gastrointestinal group. JAMA Oncol. 2018;4(7):1003–6. https://doi.org/10.1001/jamaoncol.2018.1080.CrossRefPubMedPubMedCentral

68.

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46. https://doi.org/10.1056/NEJMoa073149.CrossRefPubMed

69.

Kang Y-K, Kang W-K, Shin D-B, Chen J, Xiong J, Wang J, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol Off J Eur Soc Med Oncol. 2009;20(4):666–73. https://doi.org/10.1093/annonc/mdn717.CrossRef

70.

Lordick F, Lorenzen S, Yamada Y, Ilson D. Optimal chemotherapy for advanced gastric cancer: is there a global consensus? Gastric Cancer. 2014;17(2):213–25. https://doi.org/10.1007/s10120-013-0297-z.CrossRefPubMed

71.

Loree JM, Sha A, Soleimani M, Kennecke HF, Ho MY, Cheung WY, et al. Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III Colon Cancer. Clin Colorectal Cancer. 2018;17(2):156–63. https://doi.org/10.1016/j.clcc.2018.01.010.CrossRefPubMed

72.

Del Re M, Di Paolo A, van Schaik RH, Bocci G, Simi P, Falcone A, et al. Dihydropyrimidine dehydrogenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine? EPMA J. 2010;1(3):495–502. https://doi.org/10.1007/s13167-010-0041-2.CrossRefPubMedPubMedCentral

73.

Gentile G, Botticelli A, Lionetto L, Mazzuca F, Simmaco M, Marchetti P, et al. Genotype–phenotype correlations in 5-fluorouracil metabolism: a candidate DPYD haplotype to improve toxicity prediction. Pharmacogenomics J. 2016;16(4):320–5. https://doi.org/10.1038/tpj.2015.56.CrossRefPubMed

74.

O’Donnell PH, Trubetskoy V, Nurhussein-Patterson A, Hall JP, Nath A, Huo D, et al. Clinical evaluation of germline polymorphisms associated with capecitabine toxicity in breast cancer: TBCRC-015. Breast Cancer Res Treat. 2020;181(3):623–33. https://doi.org/10.1007/s10549-020-05603-8.CrossRefPubMed

75.

Zhang X, Bai Z, Chen B, Feng J, Yan F, Jiang Z, et al. Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Chin Med J (Engl). 2012;125(5):741–6.

76.

Deenen MJ, Tol J, Burylo AM, Doodeman VD, de Boer A, Vincent A, et al. Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer. Clin Cancer Res. 2011;17(10):3455–68. https://doi.org/10.1158/1078-0432.CCR-10-2209.CrossRefPubMed

77.

Rosmarin D, Palles C, Church D, Domingo E, Jones A, Johnstone E, et al. Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(10):1031–9. https://doi.org/10.1200/JCO.2013.51.1857.CrossRef

78.

McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, et al. Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from north American gastrointestinal intergroup trial N9741. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(20):3227–33. https://doi.org/10.1200/JCO.2009.21.7943.CrossRef

79.

Goekkurt E, Al-Batran S-E, Hartmann JT, Mogck U, Schuch G, Kramer M, et al. Pharmacogenetic analyses of a phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin: a study of the arbeitsgemeinschaft internistische onkologie. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(17):2863–73. https://doi.org/10.1200/JCO.2008.19.1718.CrossRef

80.

Kim HS, Kim M-K, Chung HH, Kim JW, Park NH, Song YS, et al. Genetic polymorphisms affecting clinical outcomes in epithelial ovarian cancer patients treated with taxanes and platinum compounds: a Korean population-based study. Gynecol Oncol. 2009;113(2):264–9. https://doi.org/10.1016/j.ygyno.2009.01.002.CrossRefPubMed

81.

Booten R, Ward T, Heighway J, Ashcroft L, Morris J, Thatcher N. Glutathione-S-Transferase P1 Isoenzyme polymorphisms, platinum-based chemotherapy, and non-small cell lung Cancer. J Thorac Oncol. 2006;1(7):679–83. https://doi.org/10.1016/S1556-0864(15)30381-6.CrossRefPubMed

82.

Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot M-A. Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res. 2006;12(10):3050–6. https://doi.org/10.1158/1078-0432.CCR-05-2076.CrossRefPubMed

83.

Pastorelli R, Cerri A, Mezzetti M, Consonni E, Airoldi L. Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes. Int J Cancer. 2002;100(1):9–13. https://doi.org/10.1002/ijc.10463.CrossRefPubMed

84.

Benhamou S, Sarasin A. ERCC2/XPD gene polymorphisms and cancer risk. Mutagenesis. 2002;17(6):463–9. https://doi.org/10.1093/mutage/17.6.463.CrossRefPubMed

85.

Boige V, Mendiboure J, Pignon J-P, Loriot M-A, Castaing M, Barrois M, et al. Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal Cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. J Clin Oncol. 2010;28(15):2556–64. https://doi.org/10.1200/JCO.2009.25.2106.CrossRefPubMed

86.

Haenisch S, May K, Wegner D, Caliebe A, Cascorbi I, Siegmund W. Influence of genetic polymorphisms on intestinal expression and rifampicin-type induction of ABCC2 and on bioavailability of talinolol. Pharmacogenet Genomics. 2008;18. https://journals.lww.com/jpharmacogenetics/Fulltext/2008/04000/Influence_of_genetic_polymorphisms_on_intestinal.9.aspx(4):357–65. https://doi.org/10.1097/FPC.0b013e3282f974b7.CrossRefPubMed

87.

Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, et al. A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 1996;56(18):4124–9.PubMed

88.

Cecchin E, D’Andrea M, Lonardi S, Zanusso C, Pella N, Errante D, et al. A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen. Pharmacogenomics J. 2013;13(5):403–9. https://doi.org/10.1038/tpj.2012.31.CrossRefPubMed

89.

Han B, Gao G, Wu W, Gao Z, Zhao X, Li L, et al. Association of ABCC2 polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients. Lung Cancer. 2011;72(2):238–43. https://doi.org/10.1016/j.lungcan.2010.09.001.CrossRefPubMed

90.

Cui J-J, Wang L-Y, Zhu T, Gong W-J, Zhou H-H, Liu Z-Q, et al. Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients. Sci Rep. 2017;7(1):5082. https://doi.org/10.1038/s41598-017-05246-8.CrossRefPubMedPubMedCentral

91.

Nichetti F, Falvella FS, Miceli R, Cheli S, Gaetano R, Fucà G, et al. Is a pharmacogenomic panel useful to estimate the risk of oxaliplatin-related neurotoxicity in colorectal cancer patients? Pharmacogenomics J. 2019;19(5):465–72. https://doi.org/10.1038/s41397-019-0078-0.CrossRefPubMed

92.

Varma KA, Jayanthi M, Dubashi B, Shewade DG. Influence of DPYD*9A, DPYD*6 and GSTP1 ile105val genetic polymorphisms on Capecitabine and Oxaliplatin (CAPOX) associated toxicities in colorectal Cancer (CRC) patients. Asian Pac J Cancer Prev. 2019;20(10):3093–100. https://doi.org/10.31557/APJCP.2019.20.10.3093.CrossRef

93.

Khushman M, Patel GK, Hosein PJ, Laurini JA, Cameron D, Clarkson DR, et al. Germline pharmacogenomics of DPYD*9A (c.85T>C) variant in patients with gastrointestinal malignancies treated with fluoropyrimidines. J Gastrointest Oncol. 2018;9:416–24.CrossRefPubMedPubMedCentral

94.

Varma A, Jayanthi M, Dubashi B, Shewade DG, Sundaram R. Genetic influence of DPYD*9A polymorphism on plasma levels of 5-fluorouracil and subsequent toxicity after oral administration of capecitabine in colorectal cancer patients of south Indian origin. Drug Metab Pers Ther. 2020;0(0). https://doi.org/10.1515/dmpt-2020-0133.

95.

Botticelli A, Onesti CE, Strigari L, Occhipinti M, Di Pietro FR, Cerbelli B, et al. A nomogram to predict 5-fluorouracil toxicity: when pharmacogenomics meets the patient. Anti-Cancer Drugs. 2017;28. https://journals.lww.com/anti-cancerdrugs/Fulltext/2017/06000/A_nomogram_to_predict_5_fluorouracil_toxicity_10.aspx:551–6. https://doi.org/10.1097/CAD.0000000000000492.CrossRefPubMed

96.

Russano M, Napolitano A, Ribelli G, Iuliani M, Simonetti S, Citarella F, et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J Exp Clin Cancer Res. 2020;39(1):95. https://doi.org/10.1186/s13046-020-01601-2.CrossRefPubMedPubMedCentral

97.

Gong W, Peng J, Yin J, Li X, Zheng W, Xiao L, et al. Association between well-characterized lung cancer lncRNA polymorphisms and platinum-based chemotherapy toxicity in Chinese patients with lung cancer. Acta Pharmacol Sin. 2017;38(4):581–90. https://doi.org/10.1038/aps.2016.164.CrossRefPubMedPubMedCentral

98.

Leone P, Buonavoglia A, Fasano R, Solimando AG, De Re V, Cicco S, et al. Insights into the regulation of tumor angiogenesis by Micro-RNAs. J Clin Med. 2019;8(12). https://doi.org/10.3390/jcm8122030.

99.

Powell NR, Zhao H, Ipe J, Liu Y, Skaar TC. Mapping the miRNA-mRNA Interactome in Human Hepatocytes and Identification of Functional mirSNPs in Pharmacogenes. Clin Pharmacol Ther. 2021;n/a n/a; 10.1002/cpt.2379.

Title: A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer
Authors: Miguel Cordova-Delgado
María Loreto Bravo
Elisa Cumsille
Charlotte N. Hill
Matías Muñoz-Medel
Mauricio P. Pinto
Ignacio N. Retamal
María A. Lavanderos
Juan Francisco Miquel
Maria Rodriguez-Fernandez
Yuwei Liao
Zhiguang Li
Alejandro H. Corvalán
Ricardo Armisén
Marcelo Garrido
Luis A. Quiñones
Gareth I. Owen
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Gastric Cancer
Gastric Cancer
Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08745-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

A novel survival model based on a Ferroptosis-related gene signature for predicting overall survival in bladder cancer

Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis

Clinical utility of complex assessment with evoked potentials in acute lymphoblastic leukemia survivors: comparison of various treatment protocols

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

TINCR inhibits the proliferation and invasion of laryngeal squamous cell carcinoma by regulating miR-210/BTG2

Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer