TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A gene mutation in Mexican colorectal cancer patients

• Authors: Martha Gallegos-Arreola , Guillermo Zúñiga-González , Josefina Sánchez-López , Alondra Cruz , Valeria Peralta-Leal , Luis Figuera , Ana Puebla-Pérez , Carlos Ronquillo-Carreón , Ana Puebla-Mora
• Languages of publication: EN

Abstracts

EN

Objective: To examine the association between TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation by comparing healthy subjects with colorectal cancer (CRC) patients in the Mexican population. Method: Genotyping of the 2R/3R was performed by polymerase chain reaction (PCR) and [IVS]14+1G>A mutation by real-time PCR analysis. Results: The observed frequencies of the TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD did not indicate an increased risk for CRC (p>0.05). However we observed an association of the 2R/2R (OR 3.08, 95% CI 1.66-6.08, p=0.0017) and heterozygous (OR 1.98, 95% CI 1.32-2.97, p=0.0012) genotypes as risk factors when comparing controls and CRC patients that were also tobacco consumers. An association between the genotype and the disease was evident. The distribution of the 2R/2R genotype and hematological toxicity (adjusted OR 2.26, 95% CI 1.54-4.45, p=0.0259), heterozygous (2R/3R) with tumor stage III-IV (OR 1.81, 95% CI 1.11-2.94, p=0.020) and 2R/2R-2R/3R in non-chemotherapy response CRC patients with hematological (OR 2.3, 95% CI 1.21-4.4, p=0.014) and gastric toxicities (OR 3.11, 95% CI 1.18-8.2, p=0.035) confirmed that this factor may significantly contribute to the CRC susceptibility. Conclusion: TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population.

Keywords

EN

TYMS 2R/3R; colorectal cancer; polymorphism; DPYD [IVS]14+1G>A; Mexican population

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2018
• Volume: 65
• Issue: 2
• Pages: 227-234

Dates

published

2018

received

2017-10-10

revised

2017-12-11

accepted

2018-02-22

(unknown)

2018-06-15

Contributors

author

Martha Gallegos-Arreola

• Genetics Division, Western Biomedical Research Center, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

author

Guillermo Zúñiga-González

• Mutagenesis Laboratory, Molecular Medicine Division, Western Biomedical Research Center, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

author

Josefina Sánchez-López

• Genetics Division, Western Biomedical Research Center, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

author

Alondra Cruz

• Genetics Division, Western Biomedical Research Center, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

author

Valeria Peralta-Leal

• Facultad de Medicina e Ingeniería en Sistemas Computacionales (FMeISC), Universidad Autónoma de Tamaulipas, Matamoros, Tamaulipas, México

author

Luis Figuera

• Genetics Division, Western Biomedical Research Center, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

author

Ana Puebla-Pérez

• Inmmunopharmacology Laboratory, Exact and Engineering Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico

author

Carlos Ronquillo-Carreón

• UMAE, Specialty Hospital, Oncology Service, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

author

Ana Puebla-Mora

• UMAE, Specialty Hospital, Pathology Service, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico

References

• Adleff V, Hitre E, Köves I, Orosz Z, Hajnal A, Kralovánszky J (2004) Heterozygote deficiency in thymidylate synthase enhancer region polymorphism genotype distribution in Hungarian colorectal cancer patients. Int J Cancer 108: 852-856.doi: 10.1002/ijc.11641.
• Alberts SR, Citrin D, Schwartz D, Rodriguez M (2016) Colon, Rectal, and Anal Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/colon-rectal-and-anal-cancers/(accessed 08.11.16).
• Balboa E, Cruz R, Carracedo A, Barros F (2015) Delimiting allelic imbalance of TYMS by allele-specific analysis. Medicine (Baltimore) 94: e1091.doi: 10.1097/MD.0000000000001091.
• Bezerra AM, Sant'Ana TA, Gomes AV, de Lacerda Vidal AK, Muniz MT (2014) Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma. Mol Biol Rep 41: 7737-7742.doi: 10.1007/s11033-014-3494-x.
• Cerić T, Obralić N, Kapur-Pojskić L, Macić D, Beslija S, Pasić A, Cerić S (2010) Investigation of IVS14 + 1G > A polymorphism of DPYD gene in a group of Bosnian patients treated with 5-Fluorouracil and capecitabine. Bosn J Basic Med Sci 10: 133-139. PMCID: PMC5509399.
• Chan AT, Giovannucci EL (2010) Primary prevention of colorectal cancer. Gastroenterology 138: 2029-2043.doi: 10.1053/j.gastro.2010.01.057.
• Dunna NR, Naushad SM, Vuree S, Anuradha C, Sailaja K, Surekha D, Rao DR, Vishnupriya S (2014) Association of thymidylate synthase 5'-UTR 28bp tandem repeat and serine hydroxymethyltransfarase C1420T polymorphisms with susceptibility to acute leukemia. Asian Pac J Cancer Prev 15: 1719-1723.doi: 10.7314/APJCP.2014.15.4.1719.
• Entry 188350. Thymidylate synthetase; TYMS. OMIM. http://www.omim.org/entry/188350 (accessed 14.11.16).
• Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136: E359-E386.doi: 10.1002/ijc.29210.
• Gallegos MP, García JE, Figuera LE, Puebla AM, Morgan G, Zúñiga GM (2009) Association of the 677C → T polymorphism in the MTHFR gene with colorectal cancer in Mexican patients. Cancer Genomics Proteomics 6: 183-188.
• García S, Téllez FI, Méndez N, Uribe M (2015) Results of the first program of colorectal cancer screening in Mexico. Endoscopia 27: 59-63. doi: 10.1158/1055-9965
• Grem JL (2012) 5-Fluorinated pyrimidines. In Cancer chemotherapy and biotherapy: principles and practice. Chabner B, Longo DL, eds, 5th edn. pp. 149-210. Lippincott-Raven Publishers, Philadelphia.
• Gutiérrez IA, Puebla AM, Delgado JI, Figuera LE, Zúñiga GM, Gómez k, Ronquillo CA, Gallegos MP (2016) Association between TNF-α-308G>A and -238G>A gene polymorphisms and TNF-α serum levels in Mexican colorectal cancer patients. Genet Mol Res 15. doi: 10.4238/gmr.15028199.
• Henrikson NB, Webber EM, Goddard KA, Scrol A, Piper M, Williams MS, Zallen DT, Calonge N, Ganiats TG, Janssens AC, Zauber A, Lansdorp I, van Ballegooijen M, Whitlock EP (2015) Family history and the natural history of colorectal cancer: systematic review. Genet Med 17: 702-712.doi: 10.1038/gim.2014.188.
• Hishida A, Matsuo K, Hamajima N, Ito H, Ogura M, Kagami Y, Taji H, Morishima Y, Emi N, Tajima K (2003) Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma. Haematologica 88: 159-166.
• Johnson CM, Wei C, Ensor JE, Smolenski DJ, Amos CI, Levin B, Berry DA (2013) Meta-analyses of colorectal cancer risk factors. Cancer Causes Control 24: 1207-1222.doi: 10.1007/s10552-013-0201-5.
• Kim JW, Jeon YJ, Jang MJ, Kim JO, Chong SY, Ko KH, Hwang SG, Oh D, Oh J, Kim NK (2015) Association between folate metabolism-related polymorphisms and colorectal cancer risk. Mol Clin Oncol 3: 639-648.doi: 10.3892/mco.2015.520.
• Lee AM, Shi Q, Alberts SR, Sargent DJ, Sinicrope FA, Berenberg JL, Grothey A, Polite B, Chan E, Gill S, Kahlenberg MS, Nair SG, Shields AF, Goldberg RM, Diasio RB (2016) Association between DPYD c.1129-5923 C>G/hapB3 and severe toxicity to 5-fluorouracil-based chemotherapy in stage III colon cancer patients: NCCTG N0147 (Alliance). Pharmacogenet Genomics 26: 133-137.doi: 10.1097/FPC.0000000000000197.
• Leung HW, Chan AL (2015) Association and prediction of severe 5-fluorouracil toxicity with dihydropyrimidine dehydrogenase gene polymorphisms: A meta-analysis. Biomed Rep 3: 879-883.doi: 10.3892/br.2015.513.
• López M, Criado MT, Esteban B, López MC (2008) Toxicidad grave por 5-fluorouracilo asociada a deficiencia de dihidropirimidina deshidrogenasa. Farmacia Hospitalaria 32: 53-61.doi: 10.1016/S1130-6343(08)72810-1
• Meulendijks D, Jacobs BA, Aliev A, Pluim D, van Werkhoven E, Deenen MJ, Beijnen JH, Cats A, Schellens JH (2016) Increased risk of severe fluoropyrimidine-associated toxicity in patients carrying a G to C substitution in the first 28-bp tandem repeat of the thymidylate synthase 2R allele. Int J Cancer 138: 245-253.doi: 10.1002/ijc.29694.
• Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215.
• Pinedo HM, Peters GF (1988) Fluorouracil: biochemistry and pharmacology. J Clin Oncol 6: 1653-1664.doi: 10.1200/JCO.1988.6.10.1653.
• Pourhoseingholi MA (2014) Epidemiology and burden of colorectal cancer in Asia-Pacific region: what shall we do now? Transl Gastrointest Cancer 3: 169-173
• Qiao Z, Lou D, Ruan L (2017) TSER polymorphism is not associated with risk of pediatric acute lymphoblastic leukemia: A meta-analysis. Medicine (Baltimore) 96: e6143.doi: 10.1097/MD.0000000000006143.
• Romiti A, Roberto M, D'Antonio C, Onesti CE, Barucca V, Milano A, Gentile G, Lionetto L, Medda E, Mazzuca F, Botticelli A, Falcone R, Simmaco M, Marchetti P (2016) The TYMS-TSER polymorphism is associated with toxicity of low-dose capecitabine in patients with advanced gastrointestinal cancer. Anticancer Drugs 27: 1044-1049.doi: 10.1097/CAD.0000000000000429.
• Rosmarin D, Palles C, Pagnamenta A, Kaur K, Pita G, Martin M, Domingo E, Jones A, Howarth K, Freeman-Mills L, Johnstone E, Wang H, Love S, Scudder C, Julier P, Fernández C, Ruiz C, Carracedo A, Castellvi S, Castells A, Gonzalez A, Taylor J, Kerr R, Kerr D, Tomlinson I. (2015) A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS. Gut 64: 111-120.doi: 10.1136/gutjnl-2013-306571.
• Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, O'Donoghue DP, Moriarty M, Fennelly D, Sheahan K. (2005) Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology 47: 141-146.doi: 10.1111/j.1365-2559.2005.02176.x.
• Saif MW, Smith M, Maloney A (2016) The first case of severe takotsubo cardiomyopathy associated with 5-fluorouracil in a patient with abnormalities of both dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS) genes. Cureus 8: e783.doi: 10.7759/cureus.783.
• Sanguinetti CJ, Dias E, Simpson AJ (1994) Rapid silver staining and recovery of PCR products separated on polyacrylamide gels. Biotechniques 17: 914-921.
• Shi Q, Zhang Z, Neumann AS, Li G, Spitz MR, Wei Q (2005) Case-control analysis of thymidylate synthase polymorphisms and risk of lung cancer. Carcinogenesis 26: 649-656.doi: 10.1093/carcin/bgh351.
• Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64: 104-117.doi: 10.3322/caac.21220.
• Song MA, Brasky TM, Marian C, Weng DY, Taslim C, Llanos AA, Dumitrescu RG, Liu Z, Mason JB, Spear SL, Kallakury BV, Freudenheim JL, Shields PG (2016) Genetic variation in one-carbon metabolism in relation to genome-wide DNA methylation in breast tissue from heathy women. Carcinogenesis 37: 471-480.doi: 10.1093/carcin/bgw030.
• Sulzyc-Bielicka V, Bińczak-Kuleta A, Pioch W, Kładny J, Gziut K, Bielicki D, Ciechanowicz A (2008) 5-Fluorouracil toxicity-attributable IVS14 + 1G > A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients. Pharmacol Rep 60: 238-242.
• Tang J, Wang PP, Zhuang YY, Chen WJ, Huang FT, Zhang SN (2012) Thymidylate synthase genetic polymorphisms and cancer risk: a meta-analysis of 37 case-control studies. Chin Med J (Engl) 125: 2582-2588.
• Tecza K, Pamula J, Lanuszewska J, Grzybowska E (2016) Genetic polymorphisms and response to 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients. Oncotarget 7: 66790-66808.doi: 10.18632/oncotarget.11053.
• Trinh BN, Ong CN, Coetzee GA, Yu MC, Laird PW (2002) Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels. Hum Genet 111: 299-302.doi: 10.1007/s00439-002-0779-2.
• Wang B, Walsh SJ, Saif MW (2016) Pancytopenia and severe gastrointestinal toxicities associated with 5-fluorouracil in a patient with thymidylate synthase (TYMS) polymorphism. Cureus 8: e798.doi: 10.7759/cureus.798.
• Wang Z, Chen JQ, Liu JL, Qin XG, Huang Y (2012) Polymorphisms in ERCC1, GSTs, TS and MTHFR predict clinical outcomes of gastric cancer patients treated with platinum/5-Fu-based chemotherapy: a systematic review. BMC Gastroenterol 12: 137.doi: 10.1186/1471-230X-12-137.
• Yang YC, Wu GC, Jin L, Wang KL, Bai ZG, Wang J, Zhang ZT (2016) Association of thymidylate synthase polymorphisms with the tumor response to preoperative chemoradiotherapy in rectal cancer: a systematic review and meta-analysis. Pharmacogenomics J doi: 10.1038/tpj.2016.11.
• Zhao T, Gu D, Xu Z, Huo X, Shen L, Wang C, Tang Y, Wu P, He J, Gong W, He ML, Chen J (2015) Polymorphism in one-carbon metabolism pathway affects survival of gastric cancer patients: Large and comprehensive study. Oncotarget 6: 9564-9576.doi: 10.18632/oncotarget.3259.
• Zhu H, Yang W, Shaw N, Perloff S, Carmichael SL, Finnell RH, Shaw GM, Lammer EJ (2012) Thymidylate synthase polymorphisms and risk of cono truncal heart defects. Am J Med Genet A 158A: 2194-2203.doi: 10.1002/ajmg.a.35310.

Identifiers

DOI

10.18388/abp.2017_2338