{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:57:30Z","timestamp":1762459050580},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,4]],"date-time":"2013-03-04T00:00:00Z","timestamp":1362355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p>The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on the outcome and a substantial increase in hematologic and extra\u2010hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The <jats:italic>Xeroderma\u2010Pigmentosum group\u2010D<\/jats:italic> polymorphism at codon\u2010751 (<jats:italic>XPD\u2010Lys751Gln<\/jats:italic>) emerged as the most significant independent predictor for death\u2010 and progression\u2010risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with cisplatin\u2013docetaxel\u2013capecitabine\u2013gemcitabine and cisplatin\u2013epirubicin\u2013capecitabine\u2013gemcitabine (or EC\u2010GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of <jats:italic>XPD\u2010Lys751Gln<\/jats:italic> with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy\u2013Weinberg equilibrium, and <jats:italic>XPD\u2010Lys751Gln<\/jats:italic> was associated with differential progression\u2010free and overall\u2010survival. Multivariate analysis confirmed its prognostic significance in platinum\u2010based regimens. In particular, <jats:italic>XPD\u2010Gln751Gln<\/jats:italic> was significantly associated with risk of death (hazard ratio, HR\u2009=\u20091.7, 95% confidence interval [CI], 1.1\u20132.6, <jats:italic>p<\/jats:italic>\u2009=\u20090.011) and risk of progression (HR\u2009=\u20091.7, 95% CI, 1.1\u20132.5, <jats:italic>p<\/jats:italic>\u2009=\u20090.013). No correlation was observed in gemcitabine monotherapy\u2010treated patients. The analysis of DNA damage using extra\u2010long\u2010PCR in lymphocytes supported the association of <jats:italic>XPD\u2010Gln751Gln<\/jats:italic> with greater resistance to cisplatin\u2010induced damage. The increasing evidence of <jats:italic>XPD\u2010Lys751Gln<\/jats:italic> impact on the outcome of gemcitabine\u2013cisplatin\u2010based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer.<\/jats:p>","DOI":"10.1002\/ijc.28078","type":"journal-article","created":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T09:40:14Z","timestamp":1360230014000},"page":"1016-1022","source":"Crossref","is-referenced-by-count":25,"title":["Prognostic factors in gemcitabine\u2013cisplatin polychemotherapy regimens in pancreatic cancer: <i>XPD\u2010Lys751Gln<\/i> polymorphism strikes back"],"prefix":"10.1002","volume":"133","author":[{"given":"Amir","family":"Avan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology VU University Medical Center Amsterdam The 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