Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer.
Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer.
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DOI：
10.1038/bjc.2011.442
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发表时间：
2011-11-22
影响因子：
8.8
通讯作者：
McLeod, H. L.
中科院分区：
文献类型：
--
作者：
Thomas, F.;Motsinger-Reif, A. A.;Hoskins, J. M.;Dvorak, A.;Roy, S.;Alyasiri, A.;Myerson, R. J.;Fleshman, J. W.;Tan, B. R.;McLeod, H. L.
直肠癌患者新辅助放化疗在肿瘤反应和宿主毒性方面存在很大程度的差异。在一项前瞻性基因型导向研究中，我们进行了一项补充药物遗传学研究，以调查5-氟尿嘧啶（5-FU）和伊立替康途径相关基因的种系多态性及其与直肠癌患者新辅助放化疗的临床结果和毒性的潜在关联。对131例患者的种系DNA进行TYMS、MTHFR、DPYD、UGT1A1、ABCC1和SLCO1B1基因的10个变异基因分型。96例患者接受5-FU/放疗（RT）， 35例患者接受5-FU/RT/伊立替康治疗。评估遗传变异与不良事件、肿瘤反应、总生存率和无病生存率之间的关系。单独使用5-FU时，MTHFR 1298A>C和MTHFR二倍型（677C>T和1298A>C）与放化疗相关毒性相关。MTHFR单倍型（677C-1298C）和双倍型（CA-TA和TA-TA）分别对严重腹泻或粘膜炎的发病率有保护作用和负作用。未观察到遗传标记与药物反应之间的关联。MTHFR多态性可以潜在地预测5-FU作为单一化疗药物治疗的患者的毒性。
There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study. The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed. MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C–1298C) and diplotypes (CA–TA and TA–TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response. MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug.
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影响因子：
45.3
作者：
Gerard, Jean-Pierre;Azria, David;Conroy, Thierry
通讯作者：
Conroy, Thierry
影响因子：
45.3
作者：
Dunst, J;Reese, T;Frings, S
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Frings, S
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45.3
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Braendengen, Morten;Tveit, Kjell M.;Glimelius, Bengt
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11.5
作者：
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通讯作者：
Milano, Gerard
影响因子：
45.3
作者：
Bosset, JF;Calais, G;Collette, L
通讯作者：
Collette, L