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Sökning: WFRF:(Lacas Benjamin) > (2014) > Genetic Markers of ...

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FältnamnIndikatorerMetadata
00005020naa a2200793 4500
001oai:DiVA.org:uu-222610
003SwePub
008140411s2014 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2226102 URI
0247 a https://doi.org/10.1200/JCO.2013.51.18572 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Rosmarin, Dan4 aut
2451 0a Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens :b Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis
264 1c 2014
338 a print2 rdacarrier
520 a PURPOSE: Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain.PATIENTS AND METHODS: We tested candidate polymorphisms identified from a systematic literature search for associations with capecitabine toxicity in 927 patients with colorectal cancer in the Quick and Simple and Reliable trial (QUASAR2). We then performed meta-analysis of QUASAR2 and 16 published studies (n = 4,855 patients) to examine the polymorphisms in various FU monotherapy and combination therapy regimens.RESULTS: Global capecitabine toxicity (grades 0/1/2 v grades 3/4/5) was associated with the rare, functional DPYD alleles 2846T>A and *2A (combined odds ratio, 5.51; P = .0013) and with the common TYMS polymorphisms 5'VNTR2R/3R and 3'UTR 6bp ins-del (combined odds ratio, 1.31; P = 9.4 × 10(-6)). There was weaker evidence that these polymorphisms predict toxicity from bolus and infusional FU monotherapy. No good evidence of association with toxicity was found for the remaining polymorphisms, including several currently included in predictive kits. No polymorphisms were associated with toxicity in combination regimens.CONCLUSION: A panel of genetic biomarkers for capecitabine monotherapy toxicity would currently comprise only the four DPYD and TYMS variants above. We estimate this test could provide 26% sensitivity, 86% specificity, and 49% positive predictive value-better than most available commercial kits, but suboptimal for clinical use. The test panel might be extended to include additional, rare DPYD variants functionally equivalent to *2A and 2846A, though insufficient evidence supports its use in bolus, infusional, or combination FU. There remains a need to identify further markers of FU toxicity for all regimens.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Klinisk laboratoriemedicin0 (SwePub)302232 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Clinical Laboratory Medicine0 (SwePub)302232 hsv//eng
7001 a Palles, Claire4 aut
7001 a Church, David4 aut
7001 a Domingo, Enric4 aut
7001 a Jones, Angela4 aut
7001 a Johnstone, Elaine4 aut
7001 a Wang, Haitao4 aut
7001 a Love, Sharon4 aut
7001 a Julier, Patrick4 aut
7001 a Scudder, Claire4 aut
7001 a Nicholson, George4 aut
7001 a Gonzalez-Neira, Anna4 aut
7001 a Martin, Miguel4 aut
7001 a Sargent, Daniel4 aut
7001 a Green, Erin4 aut
7001 a McLeod, Howard4 aut
7001 a Zanger, Ulrich M4 aut
7001 a Schwab, Matthias4 aut
7001 a Braun, Michael4 aut
7001 a Seymour, Matthew4 aut
7001 a Thompson, Lindsay4 aut
7001 a Lacas, Benjamin4 aut
7001 a Boige, Valérie4 aut
7001 a Ribelles, Nuria4 aut
7001 a Afzal, Shoaib4 aut
7001 a Enghusen, Henrik4 aut
7001 a Jensen, Søren Astrup4 aut
7001 a Etienne-Grimaldi, Marie-Christine4 aut
7001 a Milano, Gérard4 aut
7001 a Wadelius, Miau Uppsala universitet,Klinisk farmakogenomik och osteoporos,Clinical pharmacogenomics4 aut0 (Swepub:uu)miawadel
7001 a Glimelius, Bengtu Uppsala universitet,Institutionen för radiologi, onkologi och strålningsvetenskap4 aut0 (Swepub:uu)bengglim
7001 a Garmo, Hansu Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)hga27600
7001 a Gusella, Milena4 aut
7001 a Lecomte, Thierry4 aut
7001 a Laurent-Puig, Pierre4 aut
7001 a Martinez-Balibrea, Eva4 aut
7001 a Sharma, Rohini4 aut
7001 a Garcia-Foncillas, Jesus4 aut
7001 a Kleibl, Zdenek4 aut
7001 a Morel, Alain4 aut
7001 a Pignon, Jean-Pierre4 aut
7001 a Midgley, Rachel4 aut
7001 a Kerr, David4 aut
7001 a Tomlinson, Ian4 aut
7102 a Uppsala universitetb Klinisk farmakogenomik och osteoporos4 org
7730 t Journal of Clinical Oncologyg 32:10, s. 1031-1039q 32:10<1031-1039x 0732-183Xx 1527-7755
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-222610
8564 8u https://doi.org/10.1200/JCO.2013.51.1857

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