MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.

In our previous paper, the chemosensitivity of human colorectal adenocarcinoma was evaluated against 12 anticancer drugs including 5-fluorouracil (5-FU), 7-ethyl-10-hydroxycamptothecin (SN-38), mitomycin C (MMC) and cisplatin (CDDP), and it was found that the anticancer drugs were effective against those with a relatively high growth rate. MMC was effective for those with a relatively high mRNA expression of the multidrug resistance-associated protein 2 (MRP2), whereas no correlation was found for the multidrug resistant transporter MDR1 and MRP1. In this study, 3 genotypes of MDR1, 4 genotypes of MRP1, and 6 genotypes of MRP2 were additionally evaluated, and it was suggested that MDR1 C3435T and MRP2 G1249A were related with the susceptibility to colorectal adenocarcinoma. The chemosensitivity against 5-FU, SN-38, MMC and CDDP was independent of MDR1 C3435T, MRP1 G2168A, and MRP2 C-24T (C3972T), possibly due to no association with the growth rate of and mRNA expression levels of MDR1, MRP1 and MRP2 in the adenocarcinoma, however, MDR1 C3435T tended to be accompanied with a higher expression of MDR1 mRNA.