[Polymorphisms of UGT1A gene and irinotecan toxicity in Chinese colorectal cancer patients].
OBJECTIVE
To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecan toxicity in colorectal cancer patients.


METHODS
70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing.


RESULTS
14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancer patients and healthy subjects.


CONCLUSIONS
Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.
Wang
Yan
Y
Cancer Center, 307 Hospital, Academy of Military Medical Sciences, Beijing 100071, China.
Xu
Jian-Ming
JM
Shen
Lin
L
Xu
Nong
N
Wang
Jin-Wan
JW
Jiao
Shun-Chang
SC
Zhang
Jing-Sheng
JS
Song
San-Tai
ST
Li
Jian
J
Bao
Han-Ying
HY
Yang
Lin
L
Li
Fang
F
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D003967:Diarrhea / Q000139:chemically induced*; D005472:Fluorouracil / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D009503:Neutropenia / Q000139:chemically induced; D011110:Polymorphism, Genetic; D055815:Young Adult
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D014453:Glucuronosyltransferase; D005472:Fluorouracil; D002166:Camptothecin