In addition to using word boundaries, it looks like you should be reading your line into a scalar before checking against it. You may already be doing this but if so, it's not obvious from the one line you posted.

Here's a small snippet that works for me. I've included the contents of my test file in __DATA__.

#!/usr/bin/perl
use strict;
use warnings;
use autodie;

open my $fh, '<', '/path/to/your/file';

print "checking against <\$fh> once per \$Variable\n";
for my $Variable ( 'node', 'post', 'Perl' )
{
    print "$Variable match\n" if ( grep /\b$Variable\b/, <$fh> );
}

seek($fh,0,0); # so we can start reading from the beginning again

print "\nchecking against each line of <\$fh>\n";
while( my $line = <$fh> ) 
{
    for my $Variable ( 'node', 'post', 'Perl' )
    {
        print "$Variable match\n" if ( grep /\b$Variable\b/, $line );
    }
}

__DATA__
node
_node
post
_post
Perl
_Perl
Perl_

__END__
Output:
checking against <$fh> once per $Variable
node match

checking against each line of <$fh>
node match
post match
Perl match
[download]