Factores preditivos da mucosite oral induzida por quimioterapia no cancro colorrectal: papel dos polimorfismos nos genes que medeiam a resposta inflamatória

Autores

Catarina Rodrigues Serviço de Oncologia Médica - Centro Oncológico, CHTMAD, EPE
Carina Pereira Universidade do Porto, Porto
Rui Medeiros Universidade do Porto, Porto
Mário Dinis-Ribeiro C.I.N.T.E.S.I.S. – Serviço de Bioestatística e Informática Médica. Faculdade de Medicina do Porto, Porto

DOI:

https://doi.org/10.31877/on.2010.14.02

Palavras-chave:

Mucosite oral, polimorfismos genéticos, cancro colorectal, quimioterapia, inflamação

Resumo

A partir de uma série consecutiva de doentes oncológicos com cancro colorrectal submetidos a quimioterapia (n=108), foi realizado um estudo de caso-controlo de forma a determinar o papel dos polimorfismos genéticos nos genes que medeiam a resposta inflamatória no processo de evolução da mucosite oral. Foram ainda incluídas outras variáveis para estudo, capazes de influenciar o risco individual para desenvolver este efeito secundário. Contudo, não foram identificadas quaisquer divergências entre géneros, idade média dos participantes, índice de massa corporal, diabetes mellitus, prótese dentária, hábitos tabágicos e alcoólicos e alterações hematológicas nos grupos caso e controlo. A mucosite oral prévia foi identificada numa grande proporção de casos (35%)
(vs 0% no grupo controlo, p≤0.001). Os portadores do alelo A na posição -308G>A no gene TNF-α (genótipos GA e AA) possuem um risco diminuído para desenvolver a mucosite oral (OR=0.266; 95%IC: 0.073-0.964) após os tratamentos de quimioterapia específicos para cancro colorrectal.
Para que se possam estabelecer medidas profiláticas e realizar diagnósticos precoces da mucosite oral em indivíduos com cancro colorrectal submetidos a quimioterapia serão necessários estudos ulteriores que incluam os factores preditivos identificados.

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Referências

Boyle, P., Langman, J.S., ABC of Colorectal Cancer: Epidemiology. BMJ 2000; 32:805-808.

Wolpin, B.M., Meyerhardt, J.A., et al., Adjuvant Treatment of Colorectal Cancer. CA A Cancer Journal for Clinicians 2007; 57:168-85.

Costa, C., Magalhães, H., et al., O Cancro e a Qualidade de vida – A Quimioterapia e outros Fármacos no combate ao Cancro. 1ª Edição,

Novartis Farma 2005. ISBN: 972-9119-94-5.

Fadda, G., Campus, G., et al., Risk factorsfor oral mucositisin paediatric oncology patientsreceiving alkylant chemotherapy. BMC Oral Health2006; 6(13): http://www.biomedcentral.com/1472-6831/6/13.

Pico, J.L., Avila-Garavito, A., et al., Mucositis: Its Occurence, Consequences, and Treatment in the Oncology Setting. The Oncologist

; 3:446-451.

Köstler, W.J., Hejna, M., et al., Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Optionsfor Prevention and

Treatment. CA Cancer J Clin 2001; 51(5):290-315.

Stone, R., Fliedner, M.C., et al., Management of oral mucositisin patients with cancer. European Journal of Oncology Nursing 2005; 9

Suppl 1:24-32.

Cheng, K.K., Oral mucositis, dysfunction, and distressin patients undergoing cancer therapy. Journal of Clinical Nursing 2007; 16(11):2114-21.

Peterson, D.E., Cariello Anna, Mucosal Damage: A Major Risk Factor for Severe Complications After Cytotoxic Therapy. Seminarsin Oncology 2004; 31(3):35-44.

Sonis, S.T., Elting, L.S., Perspectives on Cancer Therapy-Induced Mucosal Injury: Pathogenesis, Measurement, Epidemiology, and

Consequencesfor patients. Cancer Supplement 2004; 100(9):1995-2011.

Sonis, S.T., Pathobiology of Oral Mucositis: Novel insights and opportunities. J Support Oncol 2007; 5(9):3-11.

Zhang, X., Miao, X., et al., Identification of Functional Genetic Variants in Cyclooxygenase-2 and their Association with risk of Esophageal

Cancer. Gastroenterology 2005; 129:565-76.

Pereira, C.; Sousa, H.; Ferreira, P.; Fragoso, M.; Moreira-Dias, L.; Lopes C.; Medeiros, R.; Dinis-Ribeiro, M.; –765G >C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J. Gastroenterol.2006; 12:

-5478.

Kristiansen, O.P.; Nolsøe, R.L.; Larsen, L.; Gjesing, A.M.; Johannesen, J.; Larsen, Z.M.; Lykkesfeldt, A.E.; Karlsen, A.E.; Pociot, F.; Mandrup-Poulsen, T.; Association of a functional 17beta-estradiolsensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetesin

females. Hum. Mol. Genet. 2003; 12:1101-1110.

Whyte, M., Hubbard, R., et al., Increased risk of fibrosing alveolitis associated with Interleukin-1 receptor antagonist and tumor necrosis

factor-a gene polymorphisms. Am J RespCrit CareMed. 2000; 162:755-58.

Szczeklil,W., Sanak, M., et al., Functional effects and gender association of COX-2 gene polymorphism G-765Cin bronchial asthma. J Allergy Clin Immunol, 2004. 114(2):248-53.

Meyerhardt, J.A.; Catalano, P.J.; Haller, D.G.; Mayer, R.J.; Benson, A.B.; Macdonald, J.S.; Fuchs, C.S.; Influence of body massindex on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer 2003; 98:484-495.

Meyerhardt, J.A.; Catalano, P.J.; Haller, D.G.; Mayer, R.J.; Macdonald, J.S.; Benson, A.B.; Fuchs, C.S.; Impact of diabetes mellitus on outcomes in patients with colon cancer. J. Clin. Oncol. 2003; 21: 433-440.

Sloan, J.A.; Loprinzi, C.L.; Novotny, P.J.; Okuno, S.; Nair, S.; Barton, D.L.; Sex Differencesin Fluorouracil-Induced Stomatitis. J. Clin. Oncol.

; 18:412-420.

McCarthy, G.M.; Awde, J.D.; Ghandi, H.; Vincent, M.; Kocha, W.I.; Risk factors associated with mucositisin cancerpatientsreceiving

-fluorouracil. Oral Oncol. 1998; 34:484-490.

Vatay, A., Bene, L., et al., Relationship between the tumor necrosis factor alpha polymorphisms and the serum C-reactive protein levelsin

inflammatory bowel disease. Immunogenetics 2003; 55:247-52.

Baran, W., Szepietowski, J.C., et al., A -308 promoter polymorphism of tumor necrosisfactor alpha gene does not associate with the

susceptibility to psoriasis vulgaris. No difference either between psoriasistype I and type II patients. Acta DermatovenAPA 2006;

(3):113-118.

Hall, P.D.; Benko, H.; Hogan, K.R.; Stuart, R.K.; The influence ofserum tumor necrosisfactor-alpha and interleukin-6 concentrations on

nonhematologic toxicity and hematologic recovery in patients with acute myelogenousleukaemia. Exp Hematol. 1995; 23:1256-60.

Logan, R.M.; Stringer, A.M.; Bowen, J.M.; Gibson, R.J.; Sonis, S.T.; Keefe, D.M.; Serum levels of NFkappaB and pro-inflammatory cytokines

following administration of mucotoxic drugs. Cancer Biol. Ther. 2008; 7:1139-1145.

Lima, V.; Brito, G.A.; Cunha, F.Q.; Rebouças, C.G.; Falcão, B.A.; Augusto, R.F.; Souza, M.L.; Leitão, B.T.; Ribeiro, R.A.; Effects of the tumour

necrosisfactor-alpha inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositisin hamsters. Eur. J. Oral. Sci. 2005;

:210-217.

Guimarães, A.L., Correia-Silva, J.F., et al., Investigation of functional gene polymorphismsIL-1beta, IL-6, IL-10 and TNF-alpha in individuals

with recurrent aphthousstomatitis. Arch Oral Biol. 2007; 52(3):268-72.

Galbraith, G.M., Hendley, T.M., et al., Polymorphic cytokine genotypes as markers of disease severity in adult periodontitis. J Clin Periodontol. 1999; 26(11):705-9.

Shapira, L., Stabholz, A., et al., Genetic Polymorphism of the tumor necrosisfactor(TNF)-a promoter region in families with localized early-onset periodontitis. J Periodontal Res. 2001; 36(3):183-6.

Zheng, M.H.; Qiu, L.X.; Xin, Y.N.; Pan, H.F.; Shi, K.Q.; Chen, Y.P.; Tumor necrosisfactor-alpha-308A allele may have a protective effect for

chronic hepatitis B virusinfection in Mongoloid populations, Int. J. Infect. Dis. 2008;12:S62.

D. Gambhir D; Lawrence, A.; Aggarwal, A.; Misra, R.; Mandal, S.K.; Naik, S.; Association of tumor necrosisfactor alpha and IL-10 promoter

polymorphisms with rheumatoid arthritisin North Indian population. Rheumatol. Int. 2009.

Lalla, R.V.; Pilbeam, C.C.; Walsh, S.J.; Sonis, S.T.; Keefe, D.M.; Peterson, D.E.; Role of the cyclooxygenase pathway in chemotherapy-induced oral mucositis: a pilotstudy. Support Care Cancer 2009.

Lopes, N.N.; Plapler, H.; Chavantes, M.C.; Lalla, R.V.; Yoshimura, E.M.; Alves, M.T.; Cyclooxygenase-2 and vascular endothelial growth factor expression in 5-fluorouracil-induced oral mucositisin hamsters: evaluation of two low-intensity laser protocols. Support Care Cancer

; 17:1409-1415.

Zhang, X.; Miao, X.; Tan, W.; Ning, B.; Liu, Z.; Hong, Y.; et al.; Identification of functional genetic variantsin cyclooxygenase-2 and

their association with risk of esophageal cancer. Gastroenterology 2005; 129:565-576.

Zhao, D.; Xu, D.; Zhang, X.; Wang, L.; Tan, W.; Guo, Y.; et al.; Interaction of cyclooxygenase-2 variants and smoking in pancreatic cancer: a

possible role of nucleophosmin. Gastroenterology 2009; 136:1659-1668.

Ho, Y.P.; Lin, Y.C.; Yang, Y.H.; Ho, K.Y.; Wu, Y.M.; Tsai, C.C.; Cyclooxygenase-2 Gene-765 single nucleotide polymorphism as a

protective factor against periodontitisin Taiwanese. J Clin Periodontol, 2008; 35.

Xie, C.J.; Xiao, L.M.; Fan, W.H.; Xuan, D.Y.; Zhang J.C.; Common single nucleotide polymorphismsin cyclooxygenase-2 and risk ofsevere

chronic periodontitisin a Chinese population. J. Clin. Periodontol. 2009; 36:198-203.

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Publicado

10-09-2010

Como Citar

Rodrigues C, Pereira C, Medeiros R, Dinis-Ribeiro M. Factores preditivos da mucosite oral induzida por quimioterapia no cancro colorrectal: papel dos polimorfismos nos genes que medeiam a resposta inflamatória. Onco.News [Internet]. 10 de Setembro de 2010 [citado 4 de Dezembro de 2024];(14):18-25. Disponível em: https://onco.news/index.php/journal/article/view/221