Smoking is by far and away the single major cause of cancer, but being obese, drinking too much alcohol, having a poor diet and being physically inactive combined are the second major cause. Overall, 42 percent of the 659,640 new cancer cases reported in the US every year were directly caused by poor lifestyle, as were half the 265,000 annual cancer deaths, say researchers from the American Cancer Society. While there are a number of complex factors that cause cancer, an unhealthy lifestyle is one that can best be avoided.