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The actor, who starred with Meg Ryan in Sleepless in Seattle and You've Got Mail, said he would not consider playing a similar role because he disapproves of the direction the genre has taken.
He said: "Most romantic comedies now are pretty much about teenagers getting laid, so I'm not going to do that."
The 51-year-old also revealed that he hopes to receive an Oscar nomination for his role in Charlie Wilson's War because he is desperate to win a third Academy Award.
He said: "If I'm 90 and haven't scored another one, I will truly view the latter part of my career as some kind of failure."
Hanks has been nominated for Best Actor three times in addition to winning for Philadelphia in 1993 and Forrest Gump the following year.
The nominations for this year's Oscars are announced on January 22.
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