Genre

I've been thinking quite a lot recently about genre. More specifically, about how difficult it is to define the boundaries of genre. When does one genre become another? Is it possible to write a book that fits into more than one genre and appeals to fans of both?
Take the films Alien and Star Wars. One of them is definitely horror (Alien) and the other is Sci-Fi (Star Wars). Yet Alien is more grounded in the realities of science than Star Wars, which I've always fondly seen as a kind of Cowboys and Indians film that happens to be set in outer space.
My own novel Nanobite is a horror story at its core, but it is underpinned by quite a lot of science, some of which is grounded in reality and some of which was extrapolated from the facts available now. Yes, I made a few things up, but they were educated guesses based on the current level of science.
So, does this make it a horror story with sci-fi underpinnings or a work of science fiction with elements of horror?
This is where things get difficult. So many books cross multiple genres, or mix them (with varying degrees of success). Twilight is a fantastic example - it successfully melds YA fiction with elements of horror. It was so successful they invented a whole new genre of paranormal romance to categorise it.
I could list lots of permutations. Crime/supernatural blends seem to be becoming very popular at the moment; whether this is just a passing fad remains to be seen.
The question is, will blending genre fiction alienate die-hard fans of one genre who wouldn't normally read other styles? On the whole I don't think it will (although there will be those who refuse to read outside their preferred genre); I think people will embrace this expansion, and along the way discover new and exciting authors that they'd never previously considered.