Lung cancer and heart disease aren’t the only major drivers of smoking-related mortality, a new large-scale study finds. Researchers funded by the American Cancer Society have found a host of other diseases, including breast cancer and prostate cancer, along with certain infections, are killing smokers by the thousands.

In 2011, the Centers for Disease Control and Prevention estimated that 18.1 percent of all adults in the U.S. smoke. By 2020, as part of its Healthy People initiative, the CDC hopes to cut that rate by a third, and some evidence suggests the goal is realistic. Despite accounting for nearly 500,000 deaths per year, smoking is declining overall; in the last five decades, rates have fallen from a high of 42 percent in 1965 to today’s historic low. But the prevailing death rate still reveals areas for improvement.

“Smokers die, on average, more than a decade before nonsmokers,” wrote Dr. Graham Colditz, an epidemiologist from Washington University in St. Louis in a related editorial. “Years of healthy life are lost because smoking also decreases quality of life, lowers productivity in the workplace, and leads to many chronic conditions and their associated health care costs.”

We now know, for instance, that smoking leads to problems outside the lungs and cardiovascular system. Looking at data from five major studies, which included nearly a million Americans 55 and older, the latest researchers found approximately 17 percent of the deaths resulted from causes that are separate from the 21 officially recognized by the Surgeon General. The full list included: kidney failure, intestinal ischemia, hypertensive heart disease, infections, various respiratory diseases, breast cancer, and prostate cancer.

Death rates among the study population indicate an additional 60,000 deaths may be attributable to these underreported causes — a total “greater than the total number who die each year of influenza or liver disease,” said senior author of the study Dr. Eric Jacobs. Still, he and his colleagues acknowledge these causes of death aren’t formally recognized as products of smoking, despite the evidence that says they should. People who quit smoking over the course of the study faced lower mortality as a result of these causes, suggesting the risks may be reversible.

A growing school of thought has also linked smoking to numerous neurological issues, which range from minor difficulties with balance to full-blown Alzheimer’s disease. A recent study found people who smoke for several decades showed markedly thinner cortexes in their brains compared to non-smokers and people who quit. Among people who gave up the habit, layers of gray matter started to reappear, although they were nowhere near the baseline volumes of people who never smoked, even after many years following quitting.

The new data suggest the popular CDC figure of 480,000 deaths per year may actually be too low. “These associations should be investigated further and, when appropriate, taken into account when the mortality burden of smoking is investigated,” the authors wrote. The CDC already knows that smoking causes more deaths each year than firearm-related incidents, car crashes, alcohol use, drug use, and HIV combined. Now scientists need to figure out how high the ceiling really goes.

Source: Carter B, Abnet C, Feskanich D, et al. Smoking and Mortality — Beyond Established Causes. New England Journal of Medicine. 2015.