Tobacco use leads most commonly to diseases affecting the heart and lungs, with smoking being a major risk factor for heart attacks, strokese, mphysema, and cancer. Cigarette smoking increases the risk of Crohn's disease as well as the severity of the course of the disease. It is also the number one cause of bladder cancer. The smoke from tobacco elicits carcinogenic effects on the tissues of the body that are exposed to the smoke. Tobacco smoke can combine with other carcinogens present within the environment in order to produce elevated degrees of lung cancer. The World Health Organization estimate that tobacco caused 5.4 million deaths in 2004 and 100 million deaths over the course of the 20th century. Similarly, the United States Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide." Lung cancer occurs at non-smokers in 3.4 cases per 100 000 population. At people smoking 0.5 packs of cigarettes a day this figure rises to 51.4 per 100 000, 1-2 packs - up to 143.9 per 100 000 and if the intensity of smoking is over 2 packs a day - up to 217.3 per 100,000 population. Tobacco smoke can combine with other carcinogens present within the environment in order to produce elevated degrees of lung cancer. Rates of smoking have generally levelled-off or declined in the developed world. Smoking rates in the United States have dropped by half from 1965 to 2006 falling from 42% to 20.8% in adults. In the developing world, tobacco consumption is rising by 3.4% per year. Second-hand smoke presents a very real health risk, to which six hundred thousand deaths were attributed in 2004.