ABCB1, SLCO1B1 and UGT1A1 gene polymorphisms are associated with toxicity in metastatic colorectal cancer patients treated with first-line irinotecan.
We tested specific gene polymorphisms known to be involved in the irinotecan (CPT-11) metabolic pathway. The combination of at least one SLCO1B1 521 T allele, one ABCB1 1236 C allele and one UGT1A1*28 variant 7 repeat demonstrated a statistically significant association with Grade 3/4 toxicities in metastatic colorectal cancer patients.
Divison of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
Katrin E
KE
Rhodes
Wu
W
Zhang
Dongyun
D
Yang
Oliver A
OA
Press
Michael
M
Gordon
Daniel
D
Vallböhmer
Anne M
AM
Schultheis
Georg
G
Lurje
Robert D
RD
Ladner
William
W
Fazzone
Syma
S
Iqbal
Heinz-Josef
HJ
Lenz
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D027361:Organic Anion Transporters / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D000099148:UGT1A1 Enzyme; C513055:ABCB1 protein, human; C503999:SLCO1B1 protein, human