Can people really not lose weight?

All of my extended family is fat I mean like 5"6' and 350 fat. No one could even be concidered normal weight, this is not a heathy amount of chuck here and there. They all have health problems and we're talking about how all their doctors told them to lose weight but that is was "imposible no matter what they do so why try". As someone who has always been very slim side probably due to the fact I have issues keeping anything processed down, I am wondering if this could be true? Or it is a defense mechanism because they are just too scared of failure? I know the role of genetics must be real because my adoptive sister eats nothing but junk food all the time and gains no weight but can it really make you extremely obese?