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http://ir.cmu.edu.tw/ir/handle/310903500/29056
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| 題名: | Phase II trial of cisplatin, tegafur plus uracil and leucovorin as neoadjuvant chemotherapy in patients with squamous cell carcinoma of the oropharynx and hypopharynx |
| 作者: | Wang, HM;Hsueh, CT;Wang, CS;Chen, IH;Liao, CT;Tsai, MH;Yeh, SP;Chang, JTC |
| 貢獻者: | 附設醫院內科部血液腫瘤科;Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Taipei 105, Taiwan;China Med Coll Hosp, Dept Internal Med, Div Hematol Oncol, Taichung, Taiwan;Chang Gung Mem Hosp, Dept Otolaryngol Head & Neck Surg, Taipei 10591, Taiwan;China Med Coll Hosp, Dept Otolaryngol Head & Neck Surg, Taichung, Taiwan;Chang Gung Mem Hosp, Dept Radiotherapy, Taipei 10591, Taiwan |
| 日期: | 2005 |
| 上傳時間: | 2010-09-24 14:20:05 (UTC+8) |
| 出版者: | LIPPINCOTT WILLIAMS & WILKINS |
| 摘要: | Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MIHC class I polypeptide-related sequence B) (P < 10(-7)). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23-6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition. |
| 關聯: | ANTI-CANCER DRUGS 16(4):447-453 |
| 顯示於類別: | [台中附設醫院] 期刊論文
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