Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on prognosis of breast cancer patients with chemotherapy.
Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on prognosis of breast cancer patients with chemotherapy.
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二氢嘧啶脱氢酶单核苷酸多态性对乳腺癌化疗患者预后的影响
DOI：
10.18632/oncotarget.23033
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发表时间：
2017-12-19
期刊：
影响因子：
--
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Qin F;Zhang H;Huang Y;Yang L;Yu F;Liu X;Fu L;Gu F;Ma Y
定义预测治疗效果和不良事件的生物标记物是指导患者选择个性化癌症治疗的关键任务。DPD(二氢嘧啶脱氢酶，由DPYD基因编码)是氟嘧啶代谢途径的起始酶和限速酶，氟嘧啶类药物是乳腺癌常用的药物治疗方法。以往对DPYD基因多态性的研究主要集中在其与氟嘧啶类药物毒性的关系上。本研究采用标准技术对331例浸润性乳腺癌患者的肿瘤组织进行了5-DPYD单核苷酸多态性检测。我们首次研究了DPYD基因多态在乳腺癌中的预后意义。我们发现，携带DPYD c.1627A和GT；G AG/GG的非管腔乳腺癌患者，采用以氟嘧啶为基础的方案治疗的患者，总体生存期和无进展生存期比采用非氟嘧啶方案治疗的携带者要短。然而，接受TE方案治疗的非管腔DPYD c.1627A>；G AG/GG携带者的预后好于非TE方案治疗的携带者。我们的结果提示，对于DPYD c.1627A>；G AG/GG基因携带者，以TE为基础的化疗方案是合适的方案，对这些患者不推荐以氟嘧啶为基础的化疗方案。我们的发现提供了一种新的策略，将指导临床医生为乳腺癌患者选择更精确的化疗方法。
Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and fluoropyrimidines are common used drug therapies for breast cancer. Previous studies on DPYD polymorphism were mainly focused on its association with fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide polymorphisms status was detected from tumor tissues of 331 invasive breast cancer patients using standard techniques. We for the first time investigated the prognostic significance of DPYD polymorphisms in breast cancer. We demonstrated non-luminal breast cancer patients carrying DPYD c.1627A>G AG/GG treated with fluoropyrimidine-based regimen presented a shorter overall survival and progression-free survival than carriers treated with non-fluoropyrimidine regimen. However, non-luminal DPYD c.1627A>G AG/GG carriers treated with TE (taxane and anthracycline)-based regimen showed a better prognosis compared with carriers treated with non-TE regimen. Our results suggested TE-based chemotherapy was a suitable regimen for non-luminal patients with DPYD c.1627A>G AG/GG genotype and fluoropyrimidine-based regimen should not be recommended for those patients. Our findings provided a novel strategy, which will guide clinicians to choose more precise chemotherapy treatment for breast cancer patients.
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影响因子：
--
作者：
Zhao, Xiao-Qiang;Cao, Wei-Jie;Gao, Xing
通讯作者：
Gao, Xing
影响因子：
5.2
作者：
Kelemen, Linda E.;Terry, Kathryn L.;Goodman, Marc T.;Webb, Penelope M.;Bandera, Elisa V.;McGuire, Valerie;Rossing, Mary Anne;Wang, Qinggang;Dicks, Ed;Tyrer, Jonathan P.;Song, Honglin;Kupryjanczyk, Jolanta;Dansonka-Mieszkowska, Agnieszka;Plisiecka-Halasa, Joanna;Timorek, Agnieszka;Menon, Usha;Gentry-Maharaj, Aleksandra;Gayther, Simon A.;Ramus, Susan J.;Narod, Steven A.;Risch, Harvey A.;McLaughlin, John R.;Siddiqui, Nadeem;Glasspool, Rosalind;Paul, James;Carty, Karen;Gronwald, Jacek;Lubinski, Jan;Jakubowska, Anna;Cybulski, Cezary;Kiemeney, Lambertus A.;Massuger, Leon F. A. G.;Van Altena, Anne M.;Aben, Katja K. H.;Olson, Sara H.;Orlow, Irene;Cramer, Daniel W.;Levine, Douglas A.;Bisogna, Maria;Giles, Graham G.;Southey, Melissa C.;Bruinsma, Fiona;Kjaer, Susanne K.;Hogdall, Estrid;Jensen, Allan;Hogdall, Claus K.;Lundvall, Lene;Engelholm, Svend-Aage;Heitz, Florian;Du Bois, Andreas;Harter, Philipp;Schwaab, Ira;Butzow, Ralf;Nevanlinna, Heli;Pelttari, Liisa M.;Leminen, Arto;Thompson, Pamela J.;Lurie, Galina;Wilkens, Lynne R.;Lambrechts, Diether;Van Nieuwenhuysen, Els;Lambrechts, Sandrina;Vergote, Ignace;Beesley, Jonathan;Investigators, Aocs Study Grp Acs;Fasching, Peter A.;Beckmann, Matthias W.;Hein, Alexander;Ekici, Arif B.;Doherty, Jennifer A.;Wu, Anna H.;Pearce, Celeste L.;Pike, Malcolm C.;Stram, Daniel;Chang-Claude, Jenny;Rudolph, Anja;Doerk, Thilo;Duerst, Matthias;Hillemanns, Peter;Runnebaum, Ingo B.;Bogdanova, Natalia;Antonenkova, Natalia;Odunsi, Kunle;Edwards, Robert P.;Kelley, Joseph L.;Modugno, Francesmary;Ness, Roberta B.;Karlan, Beth Y.;Walsh, Christine;Lester, Jenny;Orsulic, Sandra;Fridley, Brooke L.;Vierkant, Robert A.;Cunningham, Julie M.;Wu, Xifeng;Lu, Karen;Liang, Dong;Hildebrandt, Michelle A. T.;Weber, Rachel Palmieri;Iversen, Edwin S.;Tworoger, Shelley S.;Poole, Elizabeth M.;Salvesen, Helga B.;Krakstad, Camilla;Bjorge, Line;Tangen, Ingvild L.;Pejovic, Tanja;Bean, Yukie;Kellar, Melissa;Wentzensen, Nicolas;Brinton, Louise A.;Lissowska, Jolanta;Garcia-Closas, Montserrat;Campbell, Ian G.;Eccles, Diana;Whittemore, Alice S.;Sieh, Weiva;Rothstein, Joseph H.;Anton-Culver, Hoda;Ziogas, Argyrios;Phelan, Catherine M.;Moysich, Kirsten B.;Goode, Ellen L.;Schildkraut, Joellen M.;Berchuck, Andrew;Pharoah, Paul D. P.;Sellers, Thomas A.;Brooks-Wilson, Angela;Cook, Linda S.;Le, Nhu D.
通讯作者：
Le, Nhu D.
影响因子：
3
作者：
Joerger, M.;Huitema, A. D. R.;Schellens, J. H. M.
通讯作者：
Schellens, J. H. M.
影响因子：
6.1
作者：
Zhang Xiao-ping;Bai Zhi-bin;Wang Shuai
通讯作者：
Wang Shuai
影响因子：
4.6
作者：
Huang L;Chen F;Chen Y;Yang X;Xu S;Ge S;Fu S;Chao T;Yu Q;Liao X;Hu G;Zhang P;Yuan X
通讯作者：
Yuan X