Importance of UDP-glucuronosyltransferase 1A1*6 for irinotecan toxicities in Japanese cancer patients.
Recent pharmacogenetic studies on irinotecan have revealed the impact of UDP glucuronosyltransferase (UGT) 1A1*28 on severe irinotecan toxicities. Although the clinical role of UGT1A1*6, which is specifically detected in East Asian patients, in irinotecan toxicities is suggested, clear evidence remains limited. To examine the impact of *6, the association of UGT1A1 genotypes with severe irinotecan toxicities was retrospectively investigated in Japanese cancer patients. A significant *6-dependent increase in the incidence of grade 3 or 4 neutropenia was observed in 49 patients on irinotecan monotherapy (p=0.012). This study further clarifies the clinical importance of *6 in irinotecan therapy in East Asians.
Sai
Kimie
K
Division of Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. sai@nihs.go.jp
Saito
Yoshiro
Y
Sakamoto
Hiromi
H
Shirao
Kuniaki
K
Kurose
Koichi
K
Saeki
Mayumi
M
Ozawa
Shogo
S
Kaniwa
Nahoko
N
Hirohashi
Setsuo
S
Saijo
Nagahiro
N
Sawada
Jun-ichi
J
Yoshida
Teruhiko
T
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D001663:Bilirubin / Q000097:blood; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015994:Incidence; D000077146:Irinotecan; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D001663:Bilirubin; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme