Genetic Polymorphisms of Copper-and Platinum Drug-efflux Transporters ATP7A and ATP7B in Japanese Cancer Patients

Summary:ATP7A and ATP7B are involved in cellular resistance to platinum compounds such as cisplatin. By sequencing ATP7A, 38 genetic variations, including 30 novel ones were detected from 203 Japanese cancer patients. Of these, seven nonsynonymous variations were found: novel 1030A > G (R344G), 2111A > G (Q704R), 2200C > A (Q734K), 2948C > T (T983M) and 3112G > A (V1038I) at 0.004 frequencies and known 2299G > C (V767L) and 4390A > G (I1464V) at 0.351 and 0.075 frequencies, respectively. Regarding ATP7B, 28 novel and 33 known genetic variations were detected including 13 nonsynonymous ones: novel 1258A > G (M420V), 1426G > A (A476T), and 2401A > C (T801P) were found at 0.002, 0.005, and 0.002, respectively and known 1216G > T (A406S), 1366G > C (V456L), 2495A > G (K832R), 2785A > G (I929V), 2855G > A (R952K), 2871delC (P957PfsX9), 3419 T > C (V1140A), 3836A > G (D1279G), 3886G > A (D1296N) and 3889G > A (V1297I) at 0.483, 0.463, 0.387, 0.005, 0.384, 0.005, 0.387, 0.002, 0.012, and 0.015 frequencies, respectively. Linkage disequilibrium between detected variations was also analyzed. Our results would provide fundamental and useful information for genotyping ATP7A and ATP7B in the Japanese and probably other Asian populations.