title: MDR1 haplotype frequencies in Japanese and Caucasian, and in Japanese patients with colorectal cancer and esophageal cancer.
abstract: The genotype frequencies of MDR1 T-129C, C1236T, G2677A,T and C3435T SNPs were compared in 154 healthy Japanese and 100 healthy Caucasians to provide basic information on the inter-ethnic differences of pharmacotherapeutic outcome. The variants were found at allelic frequencies of 5.5%, 65.6%, 16.6%, 40.6% and 40.6%, for T-129C, C1236T, G2677A, G2677T and C3435T, respectively, in Japanese, and at 5.1%, 45.9%, 3.6%, 46.4% and 56.6%, respectively, in Caucasians, with a statistically significant difference for C1236T, G2677A,T and C3435T (p<0.001). G2677A was about 5-fold more frequent in Japanese than Caucasians. These genotype frequencies were also investigated in 95 Japanese patients with colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC), but no significant difference was detected, when compared with healthy Japanese subjects. The haplotype frequency reached a total of about 85% in Japanese with the following 4 major haplotypes; T(-129)-T1236-T2677-T3435 (36.1%), T(-129)-T1236-G2677-C3435 (22.5%), T(-129)-C1236-G2677-C3435 (14.2%) and T(-129)-C1236-A2677-C3435 (13.3%). The second and fourth haplotypes were hardly inferred in Caucasian, whereas T(-129)-C1236-G2677-T3435 (12.8%) was found to be Caucasian-specific. There was a tendency for higher frequencies of the T(-129)/C-(129)-C1236-A2677-C3435 haplotype in Japanese CRC patients and T(-129)-T1236-T2677-T3435 haplotype in Japanese ESCC patients, compared with that in healthy Japanese subjects.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Komoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kroetz
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Omatsu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Koyama
authors.forename: Noboru
authors.initials: N
authors.lastname: Okamura
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Aoyama
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D044465:White People
chemical_list: D000970:Antineoplastic Agents; D004247:DNA