Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

British Journal of Cancer

Volumn 105, Issue 11, 2011, Pages 1654-1662

  Thomas, F ^a,b   Motsinger Reif, A A ^a,c   Hoskins, J M ^a   Dvorak, A ^a   Roy, S ^c   Alyasiri, A ^d   Myerson, R J ^d   Fleshman, J W ^d   Tan, B R ^d   McLeod, H L ^a,d  

^a UNC Hamner Institute for Drug Safety Sciences   (United States)

^b UNIVERSITÉ DE TOULOUSE   (France)

^c NORTH CAROLINA STATE UNIVERSITY   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

5 FU; diarrhoea; MTHFR polymorphisms; mucositis; neoadjuvant chemoradiation; rectal cancer

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); FLUOROURACIL; IRINOTECAN;

ARTICLE; CHEMORADIOTHERAPY; CONTINUOUS INFUSION; DIARRHEA; DISEASE FREE SURVIVAL; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HUMAN; MAJOR CLINICAL STUDY; MUCOSA INFLAMMATION; OVERALL SURVIVAL; PHARMACOGENETICS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RECTUM CANCER; TREATMENT OUTCOME;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CAMPTOTHECIN; CHEMORADIOTHERAPY, ADJUVANT; DISEASE-FREE SURVIVAL; FLUOROURACIL; GENOTYPE; HUMANS; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MIDDLE AGED; PHARMACOGENETICS; POLYMORPHISM, GENETIC; PROSPECTIVE STUDIES; RADIATION-SENSITIZING AGENTS; RECTAL NEOPLASMS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 81955165196     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2011.442     Document Type: Article

References (50)

1. Aschele C, Pinto C, Cordio S, Rosati G, Tagliagambe A, Artale S, Rosetti P, Lonardi S, Boni L, Cionini L (2009) Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial. J Clin Oncol (Meeting Abstracts) 27: CRA4008
2. Bagley PJ, Selhub J (1998) A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 95: 13217-13220 (Pubitemid 28509551)
3. Balboa E, Duran G, LamasMJ, Gomez-Caamano A, Celeiro-Munoz C, Lopez R, Carracedo A, Barros F (2010) Pharmacogenetic analysis in neoadjuvant chemoradiation for rectal cancer: high incidence of somatic mutations and their relation with response. Pharmacogenomics 11: 747-761
4. Bertolini F, Chiara S, Bengala C, Antognoni P, Dealis C, Zironi S, Malavasi N, Scolaro T, Depenni R, Jovic G, Sonaglio C, Rossi A, Luppi G, Conte PF (2009) Neoadjuvant treatment with single-agent cetuximab followed by 5-FU, cetuximab, and pelvic radiotherapy: a phase II study in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 73: 466-472
5. Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Briffaux A, Collette L (2005) Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results-EORTC 22921. J Clin Oncol 23: 5620-5627
6. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355: 1114-1123 (Pubitemid 44394918)
7. Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Pahlman L, Wiig JN, Bystrom P, Bujko K, Glimelius B (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26: 3687-3694
8. Capitain O, Boisdron-Celle M, Poirier AL, Abadie-Lacourtoisie S, Morel A, Gamelin E (2008) The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. Pharmacogenomics J 8: 256-267 (Pubitemid 352038305)
9. Cassidy J, Twelves C, Van Cutsem E, Hoff P, Bajetta E, Boyer M, Bugat R, Burger U, Garin A, Graeven U, McKendric J, Maroun J, Marshall J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schilsky RL (2002) First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 13: 566-575 (Pubitemid 34461140)
10. Crane CH, Skibber JM, Birnbaum EH, Feig BW, Singh AK, Delclos ME, Lin EH, Fleshman JW, Thames HD, Kodner IJ, Lockett MA, Picus J, Phan T, Chandra A, Janjan NA, Read TE, Myerson RJ (2003a) The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 57: 84-89 (Pubitemid 36959742)
11. Crane CH, Skibber JM, Feig BW, Vauthey JN, Thames HD, Curley SA, Rodriguez-Bigas MA, Wolff RA, Ellis LM, Delclos ME, Lin EH, Janjan NA (2003b) Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 97: 517-524 (Pubitemid 36133820)
12. Delaneau O, Coulonges C, Zagury JF (2008) Shape-IT: new rapid and accurate algorithm for haplotype inference. BMC Bioinformatics 9: 540
13. De Mattia E, Toffoli G (2009) C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. Eur J Cancer 45: 1333-1351
14. Dunst J, Reese T, Sutter T, Zuhlke H, Hinke A, Kolling-Schlebusch K, Frings S (2002) Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol 20: 3983-3991
15. Etienne MC, Formento JL, Chazal M, Francoual M, Magne N, Formento P, Bourgeon A, Seitz JF, Delpero JR, Letoublon C, Pezet D, Milano G (2004) Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients. Pharmacogenetics 14: 785-792 (Pubitemid 40054334)
16. Garcia-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA (2003) A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 46: 298-304 (Pubitemid 36331646)
17. Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahe MA, Becouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T (2010) Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 28: 1638-1644
18. Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24: 4620-4625 (Pubitemid 46630960)
19. Gusella M, Frigo AC, Bolzonella C, Marinelli R, Barile C, Bononi A, Crepaldi G, Menon D, Stievano L, Toso S, Pasini F, Ferrazzi E, Padrini R (2009) Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer. Br J Cancer 100: 1549-1557
20. Horie N, Aiba H, Oguro K, Hojo H, Takeishi K (1995) Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 50-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct 20: 191-197
21. Hoskins JM, Goldberg RM, Qu P, Ibrahim JG, McLeod HL (2007) UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst 99: 1290-1295 (Pubitemid 47394168)
22. Innocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramirez J, Relling M, Chen P, Das S, Rosner GL, Ratain MJ (2009) Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol 27: 2604-2614
23. Kaneda S, Takeishi K, Ayusawa D, Shimizu K, Seno T, Altman S (1987) Role in translation of a triple tandemly repeated sequence in the 50-untranslated region of human thymidylate synthase mRNA. Nucleic Acids Res 15: 1259-1270 (Pubitemid 17012904)
24. Kawakami K, Omura K, Kanehira E, Watanabe Y (1999) Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res 19: 3249-3252 (Pubitemid 30042617)
25. Kawakami K, Salonga D, Park JM, Danenberg KD, Uetake H, Brabender J, Omura K, Watanabe G, Danenberg PV (2001) Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression. Clin Cancer Res 7: 4096-4101 (Pubitemid 34044633)
26. Kawakami K, Watanabe G (2003) Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res 63: 6004-6007 (Pubitemid 37187503)
27. Kim TW, Innocenti F (2007) Insights, challenges, and future directions in irinogenetics. Ther Drug Monit 29: 265-270 (Pubitemid 47262254)
28. Largillier R, Etienne-Grimaldi MC, Formento JL, Ciccolini J, Nebbia JF, Ginot A, Francoual M, Renee N, Ferrero JM, Foa C, Namer M, Lacarelle B, Milano G (2006) Pharmacogenetics of capecitabine in advanced breast cancer patients. Clin Cancer Res 12: 5496-5502 (Pubitemid 44497266)
29. Marsh S, Collie-Duguid ES, Li T, Liu X, McLeod HL (1999) Ethnic variation in the thymidylate synthase enhancer region polymorphism among Caucasian and Asian populations. Genomics 58: 310-312 (Pubitemid 29300314)
30. Marsh S, King CR, Garsa AA, McLeod HL (2005) Pyrosequencing of clinically relevant polymorphisms. Methods Mol Biol 311: 97-114
31. McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Thibodeau SN, Grothey A, Morton RF, Goldberg RM (2010) Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol 28: 3227-3233
32. Mohiuddin M, Winter K, Mitchell E, Hanna N, Yuen A, Nichols C, Shane R, Hayostek C, Willett C (2006) Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol 24: 650-655 (Pubitemid 46630429)
33. Myerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, Das P, Gunderson LL, Hong TS, Kim JJJ, Willett CG, Kachnic LA (2009) Elective clinical target volumes for conformal therapy in anorectal cancer: a Radiation Therapy Oncology Group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys 74: 824-830
34. Noordhuis P, Holwerda U, Van der Wilt CL, Van Groeningen CJ, Smid K, Meijer S, Pinedo HM, Peters GJ (2004) 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers. Ann Oncol 15: 1025-1032 (Pubitemid 39089778)
35. Pullarkat ST, Stoehlmacher J, Ghaderi V, Xiong YP, Ingles SA, Sherrod A, Warren R, Tsao-Wei D, Groshen S, Lenz HJ (2001) Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 1: 65-70 (Pubitemid 33757985)
36. Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ,Wolmark N (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27: 5124-5130
37. Ruzzo A, Graziano F, Loupakis F, Rulli E, Canestrari E, Santini D, Catalano V, Ficarelli R, Maltese P, Bisonni R, Masi G, Schiavon G, Giordani P, Giustini L, Falcone A, Tonini G, Silva R, Mattioli R, Floriani I, Magnani M (2007) Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol 25: 1247-1254 (Pubitemid 46640571)
38. Ruzzo A, Graziano F, Loupakis F, Santini D, Catalano V, Bisonni R, Ficarelli R, Fontana A, Andreoni F, Falcone A, Canestrari E, Tonini G, Mari D, Lippe P, Pizzagalli F, Schiavon G, Alessandroni P, Giustini L, Maltese P, Testa E, Menichetti ET, Magnani M (2008) Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Pharmacogenomics J 8: 278-288 (Pubitemid 352038307)
39. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R (2004) Preoperative vs postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351: 1731-1740
40. Sharma R, Hoskins JM, Rivory LP, Zucknick M, London R, Liddle C, Clarke SJ (2008) Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms and toxicity to capecitabine in advanced colorectal cancer patients. Clin Cancer Res 14: 817-825 (Pubitemid 351231165)
41. Spindler KL, Nielsen JN, Lindebjerg J, Jakobsen A (2007) Germline polymorphisms may act as predictors of response to preoperative chemoradiation in locally advanced T3 rectal tumors. Dis Colon Rectum 50: 1363-1369 (Pubitemid 47472390)
42. Tan BR, Thomas F, Myerson RJ, Zehnbauer B, Trinkaus K, Malyapa RS, Mutch MG, Abbey EE, Alyasiry A, Fleshman JW, McLeod HL (2011) Thymidylate synthase genotype-directed neoadjuvant chemoradiation for patients with rectal adenocarcinoma. J Clin Oncol 29: 875-883
43. Terrazzino S, Agostini M, Pucciarelli S, Pasetto LM, Friso ML, Ambrosi A, Lisi V, Leon A, Lise M, Nitti D (2006) A haplotype of the methylenetetrahydrofolate reductase gene predicts poor tumor response in rectal cancer patients receiving preoperative chemoradiation. Pharmacogenet Genomics 16: 817-824 (Pubitemid 44632296)
44. Theodoropoulos G, Wise WE, Padmanabhan A, Kerner BA, Taylor CW, Aguilar PS, Khanduja KS (2002) T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum 45: 895-903 (Pubitemid 34761469)
45. Thomas F, Hoskins JM, Dvorak A, Tan BR, McLeod HL (2010) Detection of the G4C SNP and rare mutations in the 28-bp repeat of TYMS using gel-based capillary electrophoresis. Pharmacogenomics 11: 1751-1756
46. Tsujinaka T, Kido Y, Shiozaki H, Iijima S, Homma T, Sakaue M, Mori T (1992) Schedule-dependent inhibition of thymidylate synthase by 5-fluorouracil in gastric cancer. Cancer 70: 2761-2765
47. Valentini V, Coco C, Picciocchi A, Morganti AG, Trodella L, Ciabattoni A, Cellini F, Barbaro B, Cogliandolo S, Nuzzo G, Doglietto GB, Ambesi-Impiombato F, Cosimelli M (2002) Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys 53: 664-674 (Pubitemid 34626505)
48. Villafranca E, Okruzhnov Y, Dominguez MA, Garcia-Foncillas J, Azinovic I, Martinez E, Illarramendi JJ, Arias F, Martinez Monge R, Salgado E, Angeletti S, Brugarolas A (2001) Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 19: 1779-1786 (Pubitemid 32230880)
49. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64: 169-172 (Pubitemid 28453294)
50. Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, Shellito P, Czito BG, Wong TZ, Paulson E, Poleski M, Vujaskovic Z, Bentley R, Chen HX, Clark JW, Jain RK (2009) Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 27: 3020-3026