I work from home and would never work in an office even with a "normal" commute. Two hours on a regular basis is something else though, I think there's definitely an added risk to a long distance commute that doesn't get talked about enough.
I do work from home but I also go into an office to meet with customers and I otherwise drive on highways on a regular basis. I'm an hour drive into the nearest major city to see a play. If I commuted into my nominal office a few days a week I'm pretty sure my overall risk wouldn't be much increased.
I actually don't need to drive into the city for a day event but it still takes me 2 hours to take the train and subway.