MDR1 T-129C polymorphism can be predictive of differentiation, and thereby prognosis of colorectal adenocarcinomas in Japanese.
The expression level of MDR1 mRNA was evaluated in colorectal adenocarcinomas and adjacent noncancerous colorectal tissues obtained from 21 Japanese patients. It was lower in the former than in the latter (p=0.012), suggesting its down-regulation as a consequence of malignant transformation of colorectal tissues, possibly with the suppression of differentiation. Relatively lower expression was suggested in moderately-differentiated colorectal adenocarcinomas than well-differentiated ones, but there was no statistical difference (p=0.111). MDR1 mRNA up-regulation was found in a colorectal adenocarcinoma cell line, HCT-15, after treatment with two typical differentiating agents, sodium butyrate and all-trans retinoic acid, suggesting its involvement in the cellular events, resulting in differentiation without malignant transformation. MDR1 T-129C, but not G2677A,T and C3435T, was associated with the lower expression of MDR1 mRNA both in colorectal adenocarcinomas (p=0.040) and adjacent noncancerous colorectal tissues (p=0.023), possibly being an useful invasive marker predicting poorly-differentiated colorectal adenocarcinomas and thereby the poor prognosis of the patients, especially when no extra biopsy samples will be obtained. Further investigations with relatively large number of patients should be undertaken to confirm these preliminary results.
Koyama
Tatsuya
T
Division of Clinical Pharmacokinetics, Department of General Therapeutics, Kobe University Graduate School of Medicine, Japan.
Nakamura
Tsutomu
T
Komoto
Chiho
C
Sakaeda
Toshiyuki
T
Taniguchi
Mayuko
M
Okamura
Noboru
N
Tamura
Takao
T
Aoyama
Nobuo
N
Kamigaki
Takashi
T
Kuroda
Yoshikazu
Y
Kasuga
Masato
M
Kadoyama
Keiichi
K
Okumura
Katsuhiko
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003596:Cytosine; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D005838:Genotype; D006801:Humans; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013941:Thymine
D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003596:Cytosine; D013941:Thymine