He expired at 9.30 a.m, his office sources here said.
He was 66 and leaves behind his wife and two sons.
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"We never imagined even in our dreams that he would leave us so early in life after succumbing to such a serious ailment," he told reporters at Kochi.
Karthikeyan, who was suffering from liver cancer, had been taken to the US for treatment last year after which he was shifted to the hospital in Bengaluru.
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