{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:08:55Z","timestamp":1791079735466,"version":"4.1.0"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of DNA repair genes are associated with differential DNA repair activity and may explain interindividual differences in overall survival after therapy with platinum agents for non\u2013small-cell lung cancer (NSCLC). <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> We used polymerase chain reaction\u2013restriction fragment length polymorphism to evaluate genetic polymorphisms of the XPD (Asp312Asn) and XRCC1 (Arg399Gln) DNA repair genes in 103 patients with stage III (54%) and IV (46%) NSCLC treated with platinum-based chemotherapy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Median age was 58 years (range, 32 to 77 years), 49% were females, and there were 86 deaths. Median follow-up period was 61.9 months. Median survival time (MST) was 14.9 months; by stage, MST was 28.6 months (IIIA), 16.0 months (IIIB), and 9.3 months (IV). Genotypes were not associated with stage. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival (P = .003 and P = .07, respectively, by log-rank test). Similarly, when we compared combinations of variant alleles across both polymorphisms, we found that a greater number of variant alleles was associated with decreasing overall survival (P = .009, log-rank test). These polymorphisms independently predicted overall survival even after taking into account stage, performance status, and chemotherapy regimen. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Genetic polymorphisms in XPD and XRCC1 may be important prognostic factors in platinum-treated patients with advanced NSCLC. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2004.08.067","type":"journal-article","created":{"date-parts":[[2004,6,8]],"date-time":"2004-06-08T00:30:15Z","timestamp":1086654615000},"page":"2594-2601","source":"Crossref","is-referenced-by-count":253,"title":["<i>XPD<\/i> and <i>XRCC1<\/i> Genetic Polymorphisms Are Prognostic Factors in Advanced Non\u2014Small-Cell Lung Cancer Patients Treated With Platinum Chemotherapy"],"prefix":"10.1200","volume":"22","author":[{"given":"Sarada","family":"Gurubhagavatula","sequence":"first","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohee","family":"Park","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Wain","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Lynch","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna S.","family":"Neuberg","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Christiani","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Surgery, Massachusetts General Hospital; the Departments of Environmental Health, Epidemiology, and Biostatistics, Harvard School of Public Health; and the Dana-Farber\/Harvard Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960615)77:12<2464::AID-CNCR8>3.0.CO;2-M"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910540413"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910550604"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.52.1.23"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.3.1207"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.4.9707108"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.21.1764"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.8.1527"},{"key":"R9","unstructured":"Wei Q, Cheng L, Hong WK, et al: Reduced DNA repair capacity in lung cancer patients. Cancer Res 56:4103,1996-4107,"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-5002(02)00224-6"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1038\/35094000"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.311.7010.899"},{"key":"R13","unstructured":"Bunn PA, Kelly K: New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: A review of the literature and future directions. Clin Cancer Res 4:1087,1998-1100,"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1988.6.4.633"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Stephens RJ, Fairlamb D, Gower N, et al: The Big Lung Trial (BLT): Determining the value of cisplatin-based chemotherapy for all patients with non-small cell lung cancer (NSCLC)\u2014Preliminary results in the supportive care setting. Proc Am Soc Clin Oncol 21:2002 (abstr 1161)","DOI":"10.1016\/S0169-5002(03)91870-8"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Giaccone G: Clinical perspectives on platinum resistance. Drugs 59:9,2000-17,  (suppl 4)","DOI":"10.2165\/00003495-200059004-00002"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.14.1091"},{"key":"R18","unstructured":"Johnson SW, Stevenson JP, O'Dwyer PJ: Cisplatin and its analogues, in DeVita VT, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology (ed 6) . Philadelphia, PA, Lippincott Williams and Wilkins, pp 376,2001-388"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000762"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.14.5024"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000320)89:2<160::AID-IJC10>3.0.CO;2-J"},{"key":"R22","unstructured":"Furuta T, Ueda T, Aune G, et al: Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. Cancer Res 62:4899,2002-4902,"},{"key":"R23","unstructured":"Reed E: Cisplatin and analogs, in Chabner BA, Longo DL (eds): Cancer Chemotherapy and Biotherapy: Principles and Practice (ed 3) . New York, NY, Lippincott Williams and Wilkins, pp 447,2001-465"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-199308000-00011"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/S0305-7372(98)90056-1"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.3.453"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.4.551"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(96)90006-4"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1038\/365852a0"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.4.593"},{"key":"R31","unstructured":"Spitz MR, Wu X, Wang Y, et al: Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 61:1354,2001-1357,"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.5.965"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.6.440"},{"key":"R34","unstructured":"Diasio RB: Pharmacogenetics, in Chabner B, Longo D (eds): Cancer Chemotherapy and Biotherapy: Principles and Practice (ed 3) . New York, NY, Lippincott Williams and Wilkins, pp 998,2001-1011"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(98)00230-5"},{"key":"R36","unstructured":"McLeod H, Papageorgio C, Watters JW: Using genetic variations to optimize cancer chemotherapy. Clin Adv Hematol Oncol 1:107,2003-111,"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1517\/14622416.3.6.763"},{"key":"R38","unstructured":"Park DJ, Zhang W, Stoehlmacher J, et al: ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy. Clin Adv Hematol Oncol 1:162,2003-166,"},{"key":"R39","unstructured":"Park DJ, Stoehlmacher J, Zhang W, et al: A  gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 61:8654,2001-8658, xeroderma pigmentosum group D"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.3816\/CLC.2003.n.004"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-5002(03)00151-X"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2004.08.067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T20:50:14Z","timestamp":1653511814000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2004.08.067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,1]]},"references-count":41,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2004,7,1]]}},"alternative-id":["10.1200\/JCO.2004.08.067"],"URL":"https:\/\/doi.org\/10.1200\/jco.2004.08.067","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7,1]]}}}