{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:26:30Z","timestamp":1791134790415,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T00:00:00Z","timestamp":1317168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>The authors assessed the impact of germline polymorphisms on clinical outcome in patients with advanced nonsmall cell lung cancer (NSCLC) who received platinum\u2010gemcitabine (PG) chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>In total, 137 patients with stage IIIB\/IV NSCLC were included who received first\u2010line PG chemotherapy (74% of patients received cisplatin, and 26% received carboplatin). Twenty\u2010three germline polymorphisms that were identified in peripheral blood samples were analyzed for progression\u2010free survival (PFS), treatment response, overall survival (OS), and toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>The median PFS was 5.8 months, the median OS was 10.2 months, and 44 patients (32%) had a partial treatment response. Carriers of the excision repair cross\u2010complementation group 1 (<jats:italic>ERCC1<\/jats:italic>) mutant thymine (T) allele had a lower treatment response rate (29% vs 52%; <jats:italic>P<\/jats:italic> = .02), shorter PFS (adjusted hazard ratio [HR], 1.60; <jats:italic>P<\/jats:italic> = .04), and shorter OS (adjusted HR, 1.54; <jats:italic>P<\/jats:italic> = .05) compared with carriers of the wild\u2010type cytosine\/cytosine (CC) genotype. The xeroderma pigmentosum group A member 10 (<jats:italic>XPD10<\/jats:italic>) mutant adenine (A) allele (adjusted HR, 0.64; <jats:italic>P<\/jats:italic> = .04) and the x\u2010ray cross\u2010complementing group 1 (<jats:italic>XRCC1<\/jats:italic>) mutant guanine (G) allele (adjusted HR, 0.51; <jats:italic>P<\/jats:italic> = .02) also were independent predictors of OS. Carriers of the mutant adenosine triphosphate\u2010dependent DNA helicase Q1 (<jats:italic>RECQ1<\/jats:italic>) C allele or the mutant cytidine deaminase (<jats:italic>CDA<\/jats:italic>) C allele were more likely to experience severe leukocytopenia (26% vs 10% [<jats:italic>P<\/jats:italic> = .03] and 28% vs 11% [<jats:italic>P<\/jats:italic> = .02], respectively) compared with wild\u2010type genotype carriers. Patients who carried the homozygous mutant glutathione S\u2010transferase \u03c0 1(<jats:italic>GSTP1<\/jats:italic>) GG genotype were at considerable risk for severe platinum\u2010associated polyneuropathy (18% vs 3% in wild\u2010type vs heterozygous mutant patients, respectively; <jats:italic>P<\/jats:italic> = .01).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>To the authors' knowledge, this is the first prospective study to date in patients with advanced NSCLC describing predictive germline polymorphisms not only for the clinical activity of PG chemotherapy (<jats:italic>ERCC1, XPD10<\/jats:italic>) but also for its toxicity (<jats:italic>GSTP1, RECQ1, CDA<\/jats:italic>). Nonplatinum\u2010containing chemotherapy in carriers of the ERCC1 T allele or the XPD10 G allele should be studied prospectively. Cancer 2012;. \u00a9 2011 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.26562","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T10:41:48Z","timestamp":1317206508000},"page":"2466-2475","source":"Crossref","is-referenced-by-count":58,"title":["Germline polymorphisms in patients with advanced nonsmall cell lung cancer receiving first\u2010line platinum\u2010gemcitabine chemotherapy"],"prefix":"10.1002","volume":"118","author":[{"given":"Markus","family":"Joerger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjaak A.","family":"Burgers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Baas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egbert F.","family":"Smit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjeerd J.","family":"Haitjema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P. L.","family":"Bard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie D.","family":"Doodeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H. M.","family":"Smits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin D. R.","family":"Huitema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos H.","family":"Beijnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H. 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