As per the documentation in https://confluence.atlassian.com/display/JIRA/Creating+Issues+and+Comments+from+Email , when a mail handler process an email, it first try to locate an issue key using the summary or the in-reply-to header and happen the email that issue, otherwise creating an issue on the configured project for the mail handler.

This can cause conflict in a setup where email addresses, mail handler and project are 1 to 1.
A mail handler could add a comment to another issue which has a similar key in the subject.

It would be convenient to have an option to have a mail handler be exclusive to a project, on creation AND commenting.

The logic would be:
Search in summary or in-reply-to header for an issue key.
If key exist AND issue is the mail handler project : Add comment
Otherwise Create issue in the mail handler project